**Author details**

Madalina-Gabriela Barbu1,2† , Andreea-Elena Boboc1† , Lidia Filip1† , Oana-Larisa Bugnar1 , Dragos Cretoiu1,3, Nicolae Suciu1,4,5, Oana Daniela Toader4,5, Sanda Maria Cretoiu3 \* and Silviu-Cristian Voinea6

1 Fetal Medicine Excellence Research Center, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania

2 Department of Rehabilitation Medicine, Ellias Emergency University Hospital, Bucharest, Romania

3 Department of Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

4 Department of Obstetrics and Gynecology, Polizu Clinical Hospital, Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest, Romania

5 Division of Obstetrics, Gynecology and Neonatology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

6 Department of Surgical Oncology, Prof. Dr. Alexandru Trestioreanu Oncology Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

\*Address all correspondence to: sanda@cretoiu.ro

† Authors have contributed equally.

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**39**

*Skeletal Muscle Stem Cell Niche from Birth to Old Age DOI: http://dx.doi.org/10.5772/intechopen.93502*

> [11] Buckingham M, Montarras D. Skeletal muscle stem cells. Current Opinion in Genetics & Development.

[12] Dumont NA et al. Satellite cells and skeletal muscle regeneration. Comprehensive Physiology.

[13] Almada AE, Wagers AJ. Molecular circuitry of stem cell fate in skeletal muscle regeneration, ageing and disease. Nature Reviews. Molecular Cell

[14] Gopinath SD, Rando TA. Stem cell review series: Aging of the skeletal muscle stem cell niche. Aging Cell.

[15] Yiu EM, Kornberg AJ. Duchenne muscular dystrophy. Journal of Paediatrics and Child Health.

[16] Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood

[17] Papayannopoulou T, Scadden DT. Stem-cell ecology and stem cells in motion. Blood. 2008;**111**(8):3923-3930

[18] Holmberg J, Durbeej M. Laminin-211

Adhesion & Migration. 2013;**7**(1):111-121

[19] Spradling A, Drummond-Barbosa D,

in skeletal muscle function. Cell

Kai T. Stem cells find their niche. Nature. 2001;**414**(6859):98-104

[20] Scadden DT. The stem-cell niche as an entity of action. Nature.

[21] Yucel N, Blau HM. Chapter 18— Skeletal Muscle Stem Cells. In: Atala A et al., editors. Principles of Regenerative

2006;**441**(7097):1075-1079

2008;**18**(4):330-336

2015;**5**(3):1027-1059

2008;**7**(4):590-598

2015;**51**(8):759-764

Cells. 1978;**4**(1-2):7-25

Biology. 2016;**17**(5):267-279

[1] Mashinchian O et al. The muscle stem cell niche in health and disease. Current Topics in Developmental

[2] Yin H, Price F, Rudnicki MA. Satellite cells and the muscle stem cell niche. Physiological Reviews.

[3] Schnyder S, Handschin C. Skeletal muscle as an endocrine organ: PGC-1alpha, myokines and exercise. Bone.

[4] Betts JG, Peter D, Eddie J, Jody EJ, Oksana K, Dean HK et al. Chapter 10.2 Skeletal Muscle—Anatomy and Physiology. 2017. Available from: https:// opentextbc.ca/anatomyandphysiology/ chapter/10-2-skeletal-muscle/ [Cited: 14

[5] Rayagiri SS et al. Basal lamina remodeling at the skeletal muscle stem cell niche mediates stem cell self-renewal. Nature Communications.

[6] Moore KA, Lemischka IR. Stem cells and their niches. Science. 2006;**311**(5769):1880-1885

[7] Henze H et al. Skeletal muscle aging—Stem cells in the spotlight. Mechanisms of Ageing and Development. 2020;**189**:111283

[8] Mauro A. Satellite cell of skeletal muscle fibers. The Journal of

Biophysical and Biochemical Cytology.

[9] Abou-Khalil R et al. Role of muscle stem cells during skeletal regeneration. Stem Cells. 2015;**33**(5):1501-1511

[10] Shi X, Garry DJ. Muscle stem cells in development, regeneration, and disease. Genes & Development.

2006;**20**(13):1692-1708

Biology. 2018;**126**:23-65

2013;**93**(1):23-67

2015;**80**:115-125

July 2020]

2018;**9**(1):1075

1961;**9**:493-495

**References**

*Skeletal Muscle Stem Cell Niche from Birth to Old Age DOI: http://dx.doi.org/10.5772/intechopen.93502*

### **References**

*Background and Management of Muscular Atrophy*

**Author details**

Oana-Larisa Bugnar1

Sanda Maria Cretoiu3

Bucharest, Romania

Romania

Madalina-Gabriela Barbu1,2†

, Andreea-Elena Boboc1†

1 Fetal Medicine Excellence Research Center, Alessandrescu-Rusescu National

2 Department of Rehabilitation Medicine, Ellias Emergency University Hospital,

3 Department of Cell and Molecular Biology and Histology, Carol Davila University

Alessandrescu-Rusescu National Institute for Mother and Child Health, Bucharest,

5 Division of Obstetrics, Gynecology and Neonatology, Carol Davila University of

6 Department of Surgical Oncology, Prof. Dr. Alexandru Trestioreanu Oncology Institute, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

\* and Silviu-Cristian Voinea6

4 Department of Obstetrics and Gynecology, Polizu Clinical Hospital,

Institute for Mother and Child Health, Bucharest, Romania

of Medicine and Pharmacy, Bucharest, Romania

Medicine and Pharmacy, Bucharest, Romania

\*Address all correspondence to: sanda@cretoiu.ro

† Authors have contributed equally.

provided the original work is properly cited.

, Lidia Filip1†

, Dragos Cretoiu1,3, Nicolae Suciu1,4,5, Oana Daniela Toader4,5,

,

**38**

[1] Mashinchian O et al. The muscle stem cell niche in health and disease. Current Topics in Developmental Biology. 2018;**126**:23-65

[2] Yin H, Price F, Rudnicki MA. Satellite cells and the muscle stem cell niche. Physiological Reviews. 2013;**93**(1):23-67

[3] Schnyder S, Handschin C. Skeletal muscle as an endocrine organ: PGC-1alpha, myokines and exercise. Bone. 2015;**80**:115-125

[4] Betts JG, Peter D, Eddie J, Jody EJ, Oksana K, Dean HK et al. Chapter 10.2 Skeletal Muscle—Anatomy and Physiology. 2017. Available from: https:// opentextbc.ca/anatomyandphysiology/ chapter/10-2-skeletal-muscle/ [Cited: 14 July 2020]

[5] Rayagiri SS et al. Basal lamina remodeling at the skeletal muscle stem cell niche mediates stem cell self-renewal. Nature Communications. 2018;**9**(1):1075

[6] Moore KA, Lemischka IR. Stem cells and their niches. Science. 2006;**311**(5769):1880-1885

[7] Henze H et al. Skeletal muscle aging—Stem cells in the spotlight. Mechanisms of Ageing and Development. 2020;**189**:111283

[8] Mauro A. Satellite cell of skeletal muscle fibers. The Journal of Biophysical and Biochemical Cytology. 1961;**9**:493-495

[9] Abou-Khalil R et al. Role of muscle stem cells during skeletal regeneration. Stem Cells. 2015;**33**(5):1501-1511

[10] Shi X, Garry DJ. Muscle stem cells in development, regeneration, and disease. Genes & Development. 2006;**20**(13):1692-1708

[11] Buckingham M, Montarras D. Skeletal muscle stem cells. Current Opinion in Genetics & Development. 2008;**18**(4):330-336

[12] Dumont NA et al. Satellite cells and skeletal muscle regeneration. Comprehensive Physiology. 2015;**5**(3):1027-1059

[13] Almada AE, Wagers AJ. Molecular circuitry of stem cell fate in skeletal muscle regeneration, ageing and disease. Nature Reviews. Molecular Cell Biology. 2016;**17**(5):267-279

[14] Gopinath SD, Rando TA. Stem cell review series: Aging of the skeletal muscle stem cell niche. Aging Cell. 2008;**7**(4):590-598

[15] Yiu EM, Kornberg AJ. Duchenne muscular dystrophy. Journal of Paediatrics and Child Health. 2015;**51**(8):759-764

[16] Schofield R. The relationship between the spleen colony-forming cell and the haemopoietic stem cell. Blood Cells. 1978;**4**(1-2):7-25

[17] Papayannopoulou T, Scadden DT. Stem-cell ecology and stem cells in motion. Blood. 2008;**111**(8):3923-3930

[18] Holmberg J, Durbeej M. Laminin-211 in skeletal muscle function. Cell Adhesion & Migration. 2013;**7**(1):111-121

[19] Spradling A, Drummond-Barbosa D, Kai T. Stem cells find their niche. Nature. 2001;**414**(6859):98-104

[20] Scadden DT. The stem-cell niche as an entity of action. Nature. 2006;**441**(7097):1075-1079

[21] Yucel N, Blau HM. Chapter 18— Skeletal Muscle Stem Cells. In: Atala A et al., editors. Principles of Regenerative Medicine. 3rd ed. Boston: Academic Press; 2019. pp. 273-293

[22] Samantha P, Marc F, Jeffrey G, Dale MR, Roger L, Michael T, et al. Practice Committee of the American Society for Reproductive Medicine. Endometriosis and Infertility: A Committee Opinion. Fertility and Sterility. 2012;**98**(3):591-598

[23] Endo T. Molecular mechanisms of skeletal muscle development, regeneration, and osteogenic conversion. Bone. 2015;**80**:2-13

[24] Buckingham M et al. The formation of skeletal muscle: From somite to limb. Journal of Anatomy. 2003;**202**(1):59-68

[25] Relaix F, Marcelle C. Muscle stem cells. Current Opinion in Cell Biology. 2009;**21**(6):748-753

[26] Relaix F et al. Divergent functions of murine Pax3 and Pax7 in limb muscle development. Genes & Development. 2004;**18**(9):1088-1105

[27] Kassar-Duchossoy L et al. Pax3/ Pax7 mark a novel population of primitive myogenic cells during development. Genes & Development. 2005;**19**(12):1426-1431

[28] De Angelis L et al. Skeletal myogenic progenitors originating from embryonic dorsal aorta coexpress endothelial and myogenic markers and contribute to postnatal muscle growth and regeneration. The Journal of Cell Biology. 1999;**147**(4):869-878

[29] Ferrari G et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science. 1998;**279**(5356):1528-1530

[30] Grigoriadis AE, Heersche JN, Aubin JE. Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone-derived clonal cell population: Effect of dexamethasone.

The Journal of Cell Biology. 1988;**106**(6):2139-2151

[31] Dellavalle A et al. Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nature Cell Biology. 2007;**9**(3):255-267

[32] Berry SE et al. Multipotential mesoangioblast stem cell therapy in the mdx/utrn−/− mouse model for Duchenne muscular dystrophy. Regenerative Medicine. 2007;**2**(3):275-288

[33] Goodell MA et al. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. The Journal of Experimental Medicine. 1996;**183**(4):1797-1806

[34] Di Rocco G et al. Myogenic potential of adipose-tissue-derived cells. Journal of Cell Science. 2006;**119**(Pt 14): 2945-2952

[35] Otto A, Collins-Hooper H, Patel K. The origin, molecular regulation and therapeutic potential of myogenic stem cell populations. Journal of Anatomy. 2009;**215**(5):477-497

[36] Katz B. The terminations of the afferent nerve fibre in the muscle spindle of the frog. Philosophical Transactions of the Royal Society of London Series B, Biological Sciences. 1961;**243**(703):221-240

[37] Ishikawa H. Electron microscopic observations of satellite cells with special reference to the development of mammalian skeletal muscles. Zeitschrift für Anatomie und Entwicklungsgeschichte. 1966;**125**(1):43-63

[38] Moss FP, Leblond CP. Satellite cells as the source of nuclei in muscles of growing rats. The Anatomical Record. 1971;**170**(4):421-435

**41**

*Skeletal Muscle Stem Cell Niche from Birth to Old Age DOI: http://dx.doi.org/10.5772/intechopen.93502*

> [49] Alfaro LAS et al. CD34 promotes satellite cell motility and entry into proliferation to facilitate efficient skeletal muscle regeneration. Stem Cells. 2011;**29**(12):2030-2041

[50] McCune BK et al. Expression of transforming growth factor-beta isoforms in small round cell tumors of childhood. An immunohistochemical study. The American Journal of Pathology. 1993;**142**(1):49-58

[51] Mourkioti F, Rosenthal N.

2005;**26**:535-542

1993;**3**:210-256

Rosenthal NIGF-1, inflammation and stem cells: Interactions during muscle regeneration. Trends in Immunology.

[52] Chen SE, Jin B, Li YP. TNF-alpha regulates myogenesis and muscle regeneration by activating p38 MAPK. American Journal of Physiology. Cell Physiology. 2007;**292**(5):C1660-C1671

[53] Grounds M, Yablonka-Reuveni Z. Molecular and cell biology of muscle dystrophy. Molecular and Cell Biology of Human Diseases Series.

[54] Füchtbauer EM, Westphal H, Fuchtbauer EM, Westphal H. MyoD and myogenin are coexpressed in regenerating

Developmental Dynamics: An Official Publication of the American Association

skeletal muscle of the mouse.

of Anatomists. 1992;**193**:34-39

[56] Buckingham M. Myogenic progenitor cells and skeletal myogenesis in vertebrates. Current Opinion in Genetics & Development.

[57] Brack AS et al. A temporal switch from notch to Wnt signaling in muscle stem cells is necessary for normal

2006;**16**(5):525-532

[55] McCroskery S et al. Myostatin negatively regulates satellite cell activation and self-renewal. Journal of Cell Biology. 2003;**162**(6):1135-1147

[39] Reznik M. Thymidine-3H uptake by satellite cells of regenerating skeletal muscle. The Journal of Cell Biology.

[40] Konigsberg IR. Clonal analysis

formation in regenerating rat skeletal muscle injured by mincing. II. An autoradiographic study. The Anatomical

1969;**40**(2):568-571

of myogenesis. Science. 1963;**140**(3573):1273-1284

[41] Snow MH. Myogenic cell

Record. 1977;**188**(2):201-217

Biology. 1969;**4**:37-77

The Anatomical Record. 1975;**182**(2):215-235

[42] Yaffe D. Cellular aspects of muscle differentiation in vitro. Current Topics in Developmental

[43] Bischoff R. Regeneration of single skeletal muscle fibers in vitro.

[44] Konigsberg UR, Lipton BH, Konigsberg IR. The regenerative response of single mature muscle fibers isolated in vitro. Developmental

[45] Jang YC et al. Skeletal muscle stem cells: Effects of aging and metabolism on muscle regenerative function. Cold Spring Harbor Symposia on Quantitative Biology. 2011;**76**:101-111

[46] Snow MH. Myogenic cell formation in regenerating rat skeletal muscle injured by mincing. I. A fine structural

study. The Anatomical Record.

[47] Darr KC, Schultz E. Exerciseinduced satellite cell activation in growing and mature skeletal muscle. Journal of Applied Physiology (1985).

[48] Rodgers JT et al. mTORC1 controls the adaptive transition of quiescent stem cells from G0 to GAlert. Nature.

1977;**188**(2):181-199

1987;**63**(5):1816-1821

2014;**510**(7505):393-396

Biology. 1975;**45**(2):260-275

*Skeletal Muscle Stem Cell Niche from Birth to Old Age DOI: http://dx.doi.org/10.5772/intechopen.93502*

[39] Reznik M. Thymidine-3H uptake by satellite cells of regenerating skeletal muscle. The Journal of Cell Biology. 1969;**40**(2):568-571

*Background and Management of Muscular Atrophy*

The Journal of Cell Biology. 1988;**106**(6):2139-2151

2007;**9**(3):255-267

2007;**2**(3):275-288

1996;**183**(4):1797-1806

2009;**215**(5):477-497

1961;**243**(703):221-240

1966;**125**(1):43-63

1971;**170**(4):421-435

observations of satellite cells with special reference to the

2945-2952

[31] Dellavalle A et al. Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nature Cell Biology.

[32] Berry SE et al. Multipotential mesoangioblast stem cell therapy in the mdx/utrn−/− mouse model for Duchenne muscular dystrophy. Regenerative Medicine.

[33] Goodell MA et al. Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. The Journal of Experimental Medicine.

[34] Di Rocco G et al. Myogenic potential of adipose-tissue-derived cells. Journal of Cell Science. 2006;**119**(Pt 14):

[35] Otto A, Collins-Hooper H, Patel K. The origin, molecular regulation and therapeutic potential of myogenic stem cell populations. Journal of Anatomy.

[36] Katz B. The terminations of the afferent nerve fibre in the muscle spindle of the frog. Philosophical Transactions of the Royal Society of London Series B, Biological Sciences.

[37] Ishikawa H. Electron microscopic

development of mammalian skeletal muscles. Zeitschrift für Anatomie und Entwicklungsgeschichte.

[38] Moss FP, Leblond CP. Satellite cells as the source of nuclei in muscles of growing rats. The Anatomical Record.

Medicine. 3rd ed. Boston: Academic

[22] Samantha P, Marc F, Jeffrey G, Dale MR, Roger L, Michael T, et al. Practice Committee of the American Society for Reproductive Medicine. Endometriosis and Infertility: A Committee Opinion. Fertility and Sterility. 2012;**98**(3):591-598

[23] Endo T. Molecular mechanisms of skeletal muscle development, regeneration, and osteogenic conversion. Bone. 2015;**80**:2-13

[24] Buckingham M et al. The formation of skeletal muscle: From somite to limb. Journal of Anatomy. 2003;**202**(1):59-68

[25] Relaix F, Marcelle C. Muscle stem cells. Current Opinion in Cell Biology.

[26] Relaix F et al. Divergent functions of murine Pax3 and Pax7 in limb muscle development. Genes & Development.

[27] Kassar-Duchossoy L et al. Pax3/ Pax7 mark a novel population of primitive myogenic cells during development. Genes & Development.

2009;**21**(6):748-753

2004;**18**(9):1088-1105

2005;**19**(12):1426-1431

[28] De Angelis L et al. Skeletal myogenic progenitors originating from embryonic dorsal aorta coexpress endothelial and myogenic markers and contribute to postnatal muscle growth and regeneration. The Journal of Cell

Biology. 1999;**147**(4):869-878

regeneration by bone marrow-derived myogenic progenitors. Science. 1998;**279**(5356):1528-1530

[30] Grigoriadis AE, Heersche JN, Aubin JE. Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone-derived clonal cell population: Effect of dexamethasone.

[29] Ferrari G et al. Muscle

Press; 2019. pp. 273-293

**40**

[40] Konigsberg IR. Clonal analysis of myogenesis. Science. 1963;**140**(3573):1273-1284

[41] Snow MH. Myogenic cell formation in regenerating rat skeletal muscle injured by mincing. II. An autoradiographic study. The Anatomical Record. 1977;**188**(2):201-217

[42] Yaffe D. Cellular aspects of muscle differentiation in vitro. Current Topics in Developmental Biology. 1969;**4**:37-77

[43] Bischoff R. Regeneration of single skeletal muscle fibers in vitro. The Anatomical Record. 1975;**182**(2):215-235

[44] Konigsberg UR, Lipton BH, Konigsberg IR. The regenerative response of single mature muscle fibers isolated in vitro. Developmental Biology. 1975;**45**(2):260-275

[45] Jang YC et al. Skeletal muscle stem cells: Effects of aging and metabolism on muscle regenerative function. Cold Spring Harbor Symposia on Quantitative Biology. 2011;**76**:101-111

[46] Snow MH. Myogenic cell formation in regenerating rat skeletal muscle injured by mincing. I. A fine structural study. The Anatomical Record. 1977;**188**(2):181-199

[47] Darr KC, Schultz E. Exerciseinduced satellite cell activation in growing and mature skeletal muscle. Journal of Applied Physiology (1985). 1987;**63**(5):1816-1821

[48] Rodgers JT et al. mTORC1 controls the adaptive transition of quiescent stem cells from G0 to GAlert. Nature. 2014;**510**(7505):393-396

[49] Alfaro LAS et al. CD34 promotes satellite cell motility and entry into proliferation to facilitate efficient skeletal muscle regeneration. Stem Cells. 2011;**29**(12):2030-2041

[50] McCune BK et al. Expression of transforming growth factor-beta isoforms in small round cell tumors of childhood. An immunohistochemical study. The American Journal of Pathology. 1993;**142**(1):49-58

[51] Mourkioti F, Rosenthal N. Rosenthal NIGF-1, inflammation and stem cells: Interactions during muscle regeneration. Trends in Immunology. 2005;**26**:535-542

[52] Chen SE, Jin B, Li YP. TNF-alpha regulates myogenesis and muscle regeneration by activating p38 MAPK. American Journal of Physiology. Cell Physiology. 2007;**292**(5):C1660-C1671

[53] Grounds M, Yablonka-Reuveni Z. Molecular and cell biology of muscle dystrophy. Molecular and Cell Biology of Human Diseases Series. 1993;**3**:210-256

[54] Füchtbauer EM, Westphal H, Fuchtbauer EM, Westphal H. MyoD and myogenin are coexpressed in regenerating skeletal muscle of the mouse. Developmental Dynamics: An Official Publication of the American Association of Anatomists. 1992;**193**:34-39

[55] McCroskery S et al. Myostatin negatively regulates satellite cell activation and self-renewal. Journal of Cell Biology. 2003;**162**(6):1135-1147

[56] Buckingham M. Myogenic progenitor cells and skeletal myogenesis in vertebrates. Current Opinion in Genetics & Development. 2006;**16**(5):525-532

[57] Brack AS et al. A temporal switch from notch to Wnt signaling in muscle stem cells is necessary for normal

adult myogenesis. Cell Stem Cell. 2008;**2**(1):50-59

[58] Knudsen KA, Horwitz AF. Tandem events in myoblast fusion. Developmental Biology. 1977;**58**(2):328-338

[59] Lipton BH, Konigsberg IR. A fine-structural analysis of the fusion of myogenic cells. The Journal of Cell Biology. 1972;**53**(2):348-364

[60] Rash JE, Fambrough D. Ultrastructural and electrophysiological correlates of cell coupling and cytoplasmic fusion during myogenesis in vitro. Developmental Biology. 1973;**30**(1):166-186

[61] Schultz E. Satellite cell proliferative compartments in growing skeletal muscles. Developmental Biology. 1996;**175**(1):84-94

[62] Guasch G, Blanpain C. Defining the epithelial stem cell niche in skin. Medical Science (Paris). 2004;**20**(3):265-267

[63] Tajbakhsh S. Skeletal muscle stem and progenitor cells: Reconciling genetics and lineage. Experimental Cell Research. 2005;**306**(2):364-372

[64] Collins CA, Partridge TA. Self-renewal of the adult skeletal muscle satellite cell. Cell Cycle. 2005;**4**(10):1338-1341

[65] Halevy O et al. Pattern of Pax7 expression during myogenesis in the posthatch chicken establishes a model for satellite cell differentiation and renewal. Developmental Dynamics. 2004;**231**(3):489-502

[66] Olguin HC, Olwin BB. Pax-7 up-regulation inhibits myogenesis and cell cycle progression in satellite cells: A potential mechanism for self-renewal. Developmental Biology. 2004;**275**(2):375-388

[67] Zammit PS et al. Muscle satellite cells adopt divergent fates: A mechanism for self-renewal? The Journal of Cell Biology. 2004;**166**(3):347-357

[68] LaBarge MA, Blau HM. Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell. 2002;**111**(4):589-601

[69] Farrington-Rock C et al. Chondrogenic and adipogenic potential of microvascular pericytes. Circulation. 2004;**110**(15):2226-2232

[70] Doherty MJ et al. Vascular pericytes express osteogenic potential in vitro and in vivo. Journal of Bone and Mineral Research. 1998;**13**(5):828-838

[71] Kutcher ME, Herman IM. The pericyte: Cellular regulator of microvascular blood flow. Microvascular Research. 2009;**77**(3):235-246

[72] Díaz-Manera J et al. The increase of pericyte population in human neuromuscular disorders supports their role in muscle regeneration in vivo. The Journal of Pathology. 2012;**228**(4):544-553

[73] Kohfeldt E et al. Nidogen-2: A new basement membrane protein with diverse binding properties. Edited by Holland IB. Journal of Molecular Biology. 1998;**282**(1):99-109

[74] Ghadiali RS et al. Dynamic changes in heparan sulfate during muscle differentiation and ageing regulate myoblast cell fate and FGF2 signalling. Matrix Biology. 2017;**59**:54-68

[75] Blanco-Bose WE et al. Purification of mouse primary myoblasts based on α7 integrin expression. Experimental Cell Research. 2001;**265**(2):212-220

[76] Carey DJ. Syndecans: Multifunctional cell-surface co-receptors. Biochemical Journal. 1997;**327**(1):1-16

**43**

*Skeletal Muscle Stem Cell Niche from Birth to Old Age DOI: http://dx.doi.org/10.5772/intechopen.93502*

> [86] Chazaud B et al. Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growth. The Journal of Cell Biology. 2003;**163**(5):1133-1143

[87] Germani A et al. Vascular endothelial growth factor modulates skeletal myoblast function. The American Journal of Pathology.

[88] Takahashi A et al. Myogenic Akt signaling regulates blood vessel recruitment during myofiber growth. Molecular and Cellular Biology.

2003;**163**(4):1417-1428

2002;**22**(13):4803-4814

2001;**264**(2):203-218

[89] Borisov AB, Dedkov EI,

[90] Carlson BM et al. Skeletal muscle regeneration in very old rats. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2001;**56**(5):B224-B233

Carlson BM. Interrelations of myogenic response, progressive atrophy of muscle fibers, and cell death in denervated skeletal muscle. The Anatomical Record.

[91] Sonnet C et al. Human macrophages rescue myoblasts and myotubes from apoptosis through a set of adhesion molecular systems. Journal of Cell Science. 2006;**119**(Pt 12):2497-2507

[92] Darmani H et al. Expression of nitric oxide synthase and transforming growth factor-beta in crush-injured tendon and synovium. Mediators of Inflammation. 2004;**13**(5-6):299-305

[93] Sinha-Hikim I et al. Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men. The Journal of Clinical Endocrinology and Metabolism.

[94] Jones DL, Wagers AJ. No place like home: Anatomy and function of

2006;**91**(8):3024-3033

[77] Xian X, Gopal S, Couchman JR. Syndecans as receptors and organizers of the extracellular matrix. Cell and Tissue Research. 2009;**339**(1):31

[78] Nunes AM et al. Impaired fetal muscle development and JAK-STAT activation mark disease onset and progression in a mouse model for merosin-deficient congenital muscular dystrophy. Human Molecular Genetics.

[79] Rooney JE et al. Severe muscular dystrophy in mice that lack dystrophin and α7 integrin. Journal of Cell Science.

[80] Shefer G, Wleklinski-Lee M, Yablonka-Reuveni Z. Skeletal muscle satellite cells can spontaneously enter, an alternative mesenchymal pathway. Journal of Cell Science.

[81] Pisani DF et al. The topoisomerase

essential for muscle cell differentiation.

1-interacting protein BTBD1 is

Cell Death & Differentiation.

[82] Brack AS et al. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science. 2007;**317**(5839):807-810

[83] Goldspink G et al. Age-related changes in collagen gene expression in the muscles of mdx dystrophic and normal mice. Neuromuscular Disorders.

[84] Greco AV et al. Insulin resistance in morbid obesity: Reversal with

[85] Christov C et al. Muscle satellite cells and endothelial cells: Close neighbors and privileged partners. Molecular Biology of the Cell.

intramyocellular fat depletion. Diabetes.

2004;**11**(11):1157-1165

1994;**4**(3):183-191

2002;**51**(1):144-151

2007;**18**(4):1397-1409

2017;**26**(11):2018-2033

2006;**119**(11):2185-2195

2004;**117**:5393-5404

*Skeletal Muscle Stem Cell Niche from Birth to Old Age DOI: http://dx.doi.org/10.5772/intechopen.93502*

[77] Xian X, Gopal S, Couchman JR. Syndecans as receptors and organizers of the extracellular matrix. Cell and Tissue Research. 2009;**339**(1):31

*Background and Management of Muscular Atrophy*

[67] Zammit PS et al. Muscle satellite cells adopt divergent fates: A mechanism for self-renewal? The Journal of Cell Biology. 2004;**166**(3):347-357

[68] LaBarge MA, Blau HM. Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell. 2002;**111**(4):589-601

Chondrogenic and adipogenic potential of microvascular pericytes. Circulation.

[70] Doherty MJ et al. Vascular pericytes express osteogenic potential in vitro and in vivo. Journal of Bone and Mineral Research. 1998;**13**(5):828-838

microvascular blood flow. Microvascular

[72] Díaz-Manera J et al. The increase of pericyte population in human neuromuscular disorders supports their role in muscle regeneration in vivo. The Journal of Pathology.

[73] Kohfeldt E et al. Nidogen-2: A new basement membrane protein with diverse binding properties. Edited by Holland IB. Journal of Molecular

[74] Ghadiali RS et al. Dynamic changes in heparan sulfate during muscle differentiation and ageing regulate myoblast cell fate and FGF2 signalling.

[75] Blanco-Bose WE et al. Purification of mouse primary myoblasts based on α7 integrin expression. Experimental Cell Research. 2001;**265**(2):212-220

[76] Carey DJ. Syndecans: Multifunctional cell-surface co-receptors. Biochemical

[71] Kutcher ME, Herman IM. The pericyte: Cellular regulator of

Research. 2009;**77**(3):235-246

2012;**228**(4):544-553

Biology. 1998;**282**(1):99-109

Matrix Biology. 2017;**59**:54-68

Journal. 1997;**327**(1):1-16

[69] Farrington-Rock C et al.

2004;**110**(15):2226-2232

adult myogenesis. Cell Stem Cell.

[59] Lipton BH, Konigsberg IR. A fine-structural analysis of the fusion of myogenic cells. The Journal of Cell

[60] Rash JE, Fambrough D. Ultrastructural and electrophysiological correlates of cell coupling and

cytoplasmic fusion during myogenesis in vitro. Developmental Biology.

[61] Schultz E. Satellite cell proliferative compartments in growing skeletal muscles. Developmental Biology.

[62] Guasch G, Blanpain C. Defining the epithelial stem cell niche in skin. Medical Science (Paris).

[63] Tajbakhsh S. Skeletal muscle stem and progenitor cells: Reconciling genetics and lineage. Experimental Cell

Research. 2005;**306**(2):364-372

[64] Collins CA, Partridge TA. Self-renewal of the adult skeletal muscle satellite cell. Cell Cycle.

[65] Halevy O et al. Pattern of Pax7 expression during myogenesis in the posthatch chicken establishes a model for satellite cell differentiation and renewal. Developmental Dynamics.

[66] Olguin HC, Olwin BB. Pax-7 up-regulation inhibits myogenesis and cell cycle progression in satellite cells: A potential mechanism for self-renewal. Developmental Biology.

2005;**4**(10):1338-1341

2004;**231**(3):489-502

2004;**275**(2):375-388

Biology. 1977;**58**(2):328-338

Biology. 1972;**53**(2):348-364

1973;**30**(1):166-186

1996;**175**(1):84-94

2004;**20**(3):265-267

[58] Knudsen KA, Horwitz AF. Tandem events in myoblast fusion. Developmental

2008;**2**(1):50-59

**42**

[78] Nunes AM et al. Impaired fetal muscle development and JAK-STAT activation mark disease onset and progression in a mouse model for merosin-deficient congenital muscular dystrophy. Human Molecular Genetics. 2017;**26**(11):2018-2033

[79] Rooney JE et al. Severe muscular dystrophy in mice that lack dystrophin and α7 integrin. Journal of Cell Science. 2006;**119**(11):2185-2195

[80] Shefer G, Wleklinski-Lee M, Yablonka-Reuveni Z. Skeletal muscle satellite cells can spontaneously enter, an alternative mesenchymal pathway. Journal of Cell Science. 2004;**117**:5393-5404

[81] Pisani DF et al. The topoisomerase 1-interacting protein BTBD1 is essential for muscle cell differentiation. Cell Death & Differentiation. 2004;**11**(11):1157-1165

[82] Brack AS et al. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science. 2007;**317**(5839):807-810

[83] Goldspink G et al. Age-related changes in collagen gene expression in the muscles of mdx dystrophic and normal mice. Neuromuscular Disorders. 1994;**4**(3):183-191

[84] Greco AV et al. Insulin resistance in morbid obesity: Reversal with intramyocellular fat depletion. Diabetes. 2002;**51**(1):144-151

[85] Christov C et al. Muscle satellite cells and endothelial cells: Close neighbors and privileged partners. Molecular Biology of the Cell. 2007;**18**(4):1397-1409

[86] Chazaud B et al. Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growth. The Journal of Cell Biology. 2003;**163**(5):1133-1143

[87] Germani A et al. Vascular endothelial growth factor modulates skeletal myoblast function. The American Journal of Pathology. 2003;**163**(4):1417-1428

[88] Takahashi A et al. Myogenic Akt signaling regulates blood vessel recruitment during myofiber growth. Molecular and Cellular Biology. 2002;**22**(13):4803-4814

[89] Borisov AB, Dedkov EI, Carlson BM. Interrelations of myogenic response, progressive atrophy of muscle fibers, and cell death in denervated skeletal muscle. The Anatomical Record. 2001;**264**(2):203-218

[90] Carlson BM et al. Skeletal muscle regeneration in very old rats. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2001;**56**(5):B224-B233

[91] Sonnet C et al. Human macrophages rescue myoblasts and myotubes from apoptosis through a set of adhesion molecular systems. Journal of Cell Science. 2006;**119**(Pt 12):2497-2507

[92] Darmani H et al. Expression of nitric oxide synthase and transforming growth factor-beta in crush-injured tendon and synovium. Mediators of Inflammation. 2004;**13**(5-6):299-305

[93] Sinha-Hikim I et al. Effects of testosterone supplementation on skeletal muscle fiber hypertrophy and satellite cells in community-dwelling older men. The Journal of Clinical Endocrinology and Metabolism. 2006;**91**(8):3024-3033

[94] Jones DL, Wagers AJ. No place like home: Anatomy and function of the stem cell niche. Nature Reviews. Molecular Cell Biology. 2008;**9**(1):11-21

[95] Snow MH. The effects of aging on satellite cells in skeletal muscles of mice and rats. Cell and Tissue Research. 1977;**185**(3):399-408

[96] Conboy IM et al. Notchmediated restoration of regenerative potential to aged muscle. Science. 2003;**302**(5650):1575-1577

[97] Taylor-Jones JM et al. Activation of an adipogenic program in adult myoblasts with age. Mechanisms of Ageing and Development. 2002;**123**(6):649-661

[98] Jejurikar SS et al. Aging increases the susceptibility of skeletal muscle derived satellite cells to apoptosis. Experimental Gerontology. 2006;**41**(9):828-836

[99] Robert L, Labat-Robert J. Aging of connective tissues: From genetic to epigenetic mechanisms. Biogerontology. 2000;**1**(2):123-131

[100] Schultz MB, Sinclair DA. When stem cells grow old: Phenotypes and mechanisms of stem cell aging. Development (Cambridge, England). 2016;**143**(1):3-14

[101] Tajbakhsh S, Cossu G. Establishing myogenic identity during somitogenesis. Current Opinion in Genetics & Development. 1997;**7**(5):634-641

[102] Musumeci G et al. Somitogenesis: From somite to skeletal muscle. Acta Histochemica. 2015;**117**(4-5):313-328

[103] Chargé SB, Rudnicki MA. Cellular and molecular regulation of muscle regeneration. Physiological Reviews. 2004;**84**(1):209-238

[104] Katz B. The termination of the afferent nerve fibre in the muscle spindle of the frog. Philosophical Transactions of the Royal Society of London Series B, Biological Sciences. 1961;**243**(703):221-240

[105] Forcina L et al. An overview about the biology of skeletal muscle satellite cells. Current Genomics. 2019;**20**(1):24-37

[106] Seale P et al. Pax7 is required for the specification of myogenic satellite cells. Cell. 2000;**102**(6):777-786

[107] Relaix F et al. Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells. The Journal of Cell Biology. 2006;**172**(1):91-102

[108] Irintchev A et al. Expression pattern of M-cadherin in normal, denervated, and regenerating mouse muscles. Developmental Dynamics. 1994;**199**(4):326-337

[109] Garry DJ et al. Persistent expression of MNF identifies myogenic stem cells in postnatal muscles. Developmental Biology. 1997;**188**(2):280-294

[110] Mechtersheimer G, Staudter M, Möller P. Expression of the natural killer cell-associated antigens CD56 and CD57 in human neural and striated muscle cells and in their tumors. Cancer Research. 1991;**51**(4):1300-1307

[111] Tatsumi R et al. HGF/SF is present in normal adult skeletal muscle and is capable of activating satellite cells. Developmental Biology. 1998;**194**(1):114-128

[112] Jesse TL et al. Interferon regulatory factor-2 is a transcriptional activator in muscle where it regulates expression of vascular cell adhesion molecule-1. The Journal of Cell Biology. 1998;**140**(5):1265-1276

[113] Beauchamp JR et al. Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells. The Journal of Cell Biology. 2000;**151**(6):1221-1234

**45**

*Skeletal Muscle Stem Cell Niche from Birth to Old Age DOI: http://dx.doi.org/10.5772/intechopen.93502*

[123] Bischoff R, Heintz C. Enhancement

of skeletal muscle regeneration. Development Dynamics. 1994;**201**(1):

[124] Bischoff R. Interaction between satellite cells and skeletal muscle fibers. Development. 1990;**109**(4):943-952

[125] Collins CA et al. A population of myogenic stem cells that survives skeletal muscle aging. Stem Cells.

[126] Rochlin K, Yu S, Roy S, Baylies MK. Developmental Biology. 2010;**341**:66-83

[127] Wang YX, Rudnicki MA. Nature Reviews. Molecular Cell Biology.

[128] Cooper ST, McNeil PL. Physiological

Reviews. 2015;**95**:1205-1240

2005;**309**:2064-2067

2005;**435**:948-953

2007;**25**:2006-2016

[129] Montarras D et al. Direct isolation of satellite cells for skeletal muscle regeneration. Science.

[130] Relaix F et al. A Pax3/Pax7 dependent population of skeletal muscle progenitor cells. Nature.

[131] Gayraud-Morel B et al. A role for the myogenic determination gene Myf5 in adult regenerative myogenesis. Developmental Biology. 2007;**312**:13-28

[132] Ustanina S, Carvajal J, Rigby P, Braun T. The myogenic factor Myf5 supports efficient skeletal muscle regeneration by enabling transient myoblast amplification. Stem Cells.

[133] Sacco A, Doyonnas R, Kraft P, Vitorovic S, Blau HM. Self-renewal and expansion of single transplanted muscle stem cells. Nature. 2008;**456**:502-506. A report demonstrating that a single satellite cell is sufficient to restore a

functional satellite cell pool

2007;**25**(4):885-894

2011;**13**:127-133

41-54

[114] Cornelison DD et al. Syndecan-3 and syndecan-4 specifically mark skeletal muscle satellite cells and are implicated in satellite cell maintenance and muscle

regeneration. Developmental Biology.

[115] Schmidt K et al. Sox8 is a specific marker for muscle satellite cells and inhibits myogenesis. The Journal of Biological Chemistry. 2003;**278**(32):29769-29775

[116] Lee HJ et al. Sox15 is required for skeletal muscle regeneration. Molecular and Cellular Biology.

[117] Sherwood RI et al. Isolation of adult mouse myogenic progenitors: Functional heterogeneity of cells within and engrafting skeletal muscle. Cell.

[118] Volonte D, Liu Y, Galbiati F. The modulation of caveolin-1 expression controls satellite cell activation during muscle repair. The FASEB Journal.

2004;**24**(19):8428-8436

2004;**119**(4):543-554

2005;**19**(2):237-239

2007;**25**(10):2448-2459

2009;**4**(4):e5205

2011;**138**(21):4609-4619

[119] Fukada S et al. Molecular signature of quiescent satellite cells in adult skeletal muscle. Stem Cells.

[120] Gnocchi VF et al. Further characterisation of the molecular signature of quiescent and activated mouse muscle satellite cells. PLoS One.

[121] Fukada S et al. Hesr1 and Hesr3 are essential to generate undifferentiated quiescent satellite cells and to maintain satellite cell numbers. Development.

[122] Dumont NA et al. Dystrophin expression in muscle stem cells regulates their polarity and asymmetric division. Nature Medicine. 2015;**21**(12):1455-1463

2001;**239**(1):79-94

*Skeletal Muscle Stem Cell Niche from Birth to Old Age DOI: http://dx.doi.org/10.5772/intechopen.93502*

[114] Cornelison DD et al. Syndecan-3 and syndecan-4 specifically mark skeletal muscle satellite cells and are implicated in satellite cell maintenance and muscle regeneration. Developmental Biology. 2001;**239**(1):79-94

*Background and Management of Muscular Atrophy*

London Series B, Biological Sciences.

[106] Seale P et al. Pax7 is required for the specification of myogenic satellite cells. Cell. 2000;**102**(6):777-786

[107] Relaix F et al. Pax3 and Pax7 have distinct and overlapping functions in adult muscle progenitor cells. The Journal of Cell Biology.

[108] Irintchev A et al. Expression pattern of M-cadherin in normal, denervated, and regenerating mouse muscles. Developmental Dynamics.

[109] Garry DJ et al. Persistent expression of MNF identifies myogenic stem cells in postnatal muscles. Developmental

[110] Mechtersheimer G, Staudter M, Möller P. Expression of the natural killer cell-associated antigens CD56 and CD57 in human neural and striated muscle cells and in their tumors. Cancer

[105] Forcina L et al. An overview about the biology of skeletal muscle satellite cells. Current Genomics.

1961;**243**(703):221-240

2019;**20**(1):24-37

2006;**172**(1):91-102

1994;**199**(4):326-337

Biology. 1997;**188**(2):280-294

Research. 1991;**51**(4):1300-1307

[111] Tatsumi R et al. HGF/SF is present in normal adult skeletal muscle and is capable of activating satellite cells. Developmental Biology.

1998;**194**(1):114-128

1998;**140**(5):1265-1276

2000;**151**(6):1221-1234

[112] Jesse TL et al. Interferon

regulatory factor-2 is a transcriptional activator in muscle where it regulates expression of vascular cell adhesion molecule-1. The Journal of Cell Biology.

[113] Beauchamp JR et al. Expression of CD34 and Myf5 defines the majority of quiescent adult skeletal muscle satellite cells. The Journal of Cell Biology.

the stem cell niche. Nature Reviews. Molecular Cell Biology. 2008;**9**(1):11-21

[95] Snow MH. The effects of aging on satellite cells in skeletal muscles of mice and rats. Cell and Tissue Research.

mediated restoration of regenerative potential to aged muscle. Science.

[97] Taylor-Jones JM et al. Activation of an adipogenic program in adult myoblasts with age. Mechanisms of Ageing and Development.

[98] Jejurikar SS et al. Aging increases the susceptibility of skeletal muscle derived satellite cells to apoptosis. Experimental Gerontology. 2006;**41**(9):828-836

[99] Robert L, Labat-Robert J. Aging of connective tissues: From genetic to epigenetic mechanisms. Biogerontology.

[100] Schultz MB, Sinclair DA. When stem cells grow old: Phenotypes and mechanisms of stem cell aging. Development (Cambridge, England).

[101] Tajbakhsh S, Cossu G. Establishing myogenic identity during somitogenesis.

[102] Musumeci G et al. Somitogenesis: From somite to skeletal muscle. Acta Histochemica. 2015;**117**(4-5):313-328

[103] Chargé SB, Rudnicki MA. Cellular and molecular regulation of muscle regeneration. Physiological Reviews.

[104] Katz B. The termination of the afferent nerve fibre in the muscle spindle of the frog. Philosophical Transactions of the Royal Society of

Current Opinion in Genetics & Development. 1997;**7**(5):634-641

1977;**185**(3):399-408

[96] Conboy IM et al. Notch-

2003;**302**(5650):1575-1577

2002;**123**(6):649-661

2000;**1**(2):123-131

2016;**143**(1):3-14

2004;**84**(1):209-238

**44**

[115] Schmidt K et al. Sox8 is a specific marker for muscle satellite cells and inhibits myogenesis. The Journal of Biological Chemistry. 2003;**278**(32):29769-29775

[116] Lee HJ et al. Sox15 is required for skeletal muscle regeneration. Molecular and Cellular Biology. 2004;**24**(19):8428-8436

[117] Sherwood RI et al. Isolation of adult mouse myogenic progenitors: Functional heterogeneity of cells within and engrafting skeletal muscle. Cell. 2004;**119**(4):543-554

[118] Volonte D, Liu Y, Galbiati F. The modulation of caveolin-1 expression controls satellite cell activation during muscle repair. The FASEB Journal. 2005;**19**(2):237-239

[119] Fukada S et al. Molecular signature of quiescent satellite cells in adult skeletal muscle. Stem Cells. 2007;**25**(10):2448-2459

[120] Gnocchi VF et al. Further characterisation of the molecular signature of quiescent and activated mouse muscle satellite cells. PLoS One. 2009;**4**(4):e5205

[121] Fukada S et al. Hesr1 and Hesr3 are essential to generate undifferentiated quiescent satellite cells and to maintain satellite cell numbers. Development. 2011;**138**(21):4609-4619

[122] Dumont NA et al. Dystrophin expression in muscle stem cells regulates their polarity and asymmetric division. Nature Medicine. 2015;**21**(12):1455-1463

[123] Bischoff R, Heintz C. Enhancement of skeletal muscle regeneration. Development Dynamics. 1994;**201**(1): 41-54

[124] Bischoff R. Interaction between satellite cells and skeletal muscle fibers. Development. 1990;**109**(4):943-952

[125] Collins CA et al. A population of myogenic stem cells that survives skeletal muscle aging. Stem Cells. 2007;**25**(4):885-894

[126] Rochlin K, Yu S, Roy S, Baylies MK. Developmental Biology. 2010;**341**:66-83

[127] Wang YX, Rudnicki MA. Nature Reviews. Molecular Cell Biology. 2011;**13**:127-133

[128] Cooper ST, McNeil PL. Physiological Reviews. 2015;**95**:1205-1240

[129] Montarras D et al. Direct isolation of satellite cells for skeletal muscle regeneration. Science. 2005;**309**:2064-2067

[130] Relaix F et al. A Pax3/Pax7 dependent population of skeletal muscle progenitor cells. Nature. 2005;**435**:948-953

[131] Gayraud-Morel B et al. A role for the myogenic determination gene Myf5 in adult regenerative myogenesis. Developmental Biology. 2007;**312**:13-28

[132] Ustanina S, Carvajal J, Rigby P, Braun T. The myogenic factor Myf5 supports efficient skeletal muscle regeneration by enabling transient myoblast amplification. Stem Cells. 2007;**25**:2006-2016

[133] Sacco A, Doyonnas R, Kraft P, Vitorovic S, Blau HM. Self-renewal and expansion of single transplanted muscle stem cells. Nature. 2008;**456**:502-506. A report demonstrating that a single satellite cell is sufficient to restore a functional satellite cell pool

[134] Collins CA et al. Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell. 2005;**122**:289-301

[135] Gussoni E et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature. 1999;**401**:390-394

[136] Benchaouir R et al. Restoration of human dystrophin following transplantation of exon-skippingengineered DMD patient stem cells into dystrophic mice. Cell Stem Cell. 2007;**1**:646-657

[137] Sampaolesi M et al. Cell therapy of alpha-sarcoglycan null dystrophic mice through intra-arterial delivery of mesoangioblasts. Science. 2003;**301**:487-492

[138] Sampaolesi M et al. Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature. 2006;**444**:574-579

[139] Torrente Y. Human circulating AC133+ stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle. Journal of Clinical Investigation. 2004;**114**:182-195

[140] Dellavalle A et al. Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells. Nature Communications. 2011;**2**:499

[141] Arnold L et al. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. The Journal of Experimental Medicine. 2007;**204**:1057-1069

[142] Sambasivan R et al. Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration. Development. 2011;**138**:3647-3656

[143] Lepper C et al. An absolute requirement for Pax7-positive satellite cells in acute injury-induced skeletal muscle regeneration. Development. 2011;**138**:3639-3646

[144] Hardy D, Besnard A, Latil M, Jouvion G, Briand D, Thepenier C, et al. Comparative study of injury models for studying muscle regeneration in mice. PLoS One. 2016;**11**:e0147198

[145] Lukjanenko L, Brachat S, Pierrel E, Lach-Trifilieff E, Feige JN. Genomic profiling reveals that transient adipogenic activation is a hallmark of mouse models of skeletal muscle regeneration. PLoS One. 2013;**8**:e71084

[146] Bischoff R. Interaction between satellite cells and skeletal muscle fibers. Development. 1990;**109**:943-952

[147] Goetsch SC, Hawke TJ, Gallardo TD, Richardson JA, Garry DJ. Transcriptional profiling and regulation of the extracellular matrix during muscle regeneration. Physiological Genomics. 2003;**14**:261-271

[148] Kherif S, Lafuma C, Dehaupas M, Lachkar S, Fournier JG, Verdiere-Sahuque M, et al. Expression of Matrix Metalloproteinases 2 and 9 in Regenerating Skeletal Muscle: A Study in Experimentally Injured and mdxMuscles. Developmental Biology. 1999;**205**:158-170

[149] Caldwell CJ, Mattey DL, Weller RO. Role of the basement membrane in the regeneration of skeletal muscle. Neuropathology and Applied Neurobiology. 1990;**16**:225-238

[150] Koskinen SO, Ahtikoski AM, Komulainen J, Hesselink MK, Drost MR, Takala TE. Short-term effects of forced eccentric contractions on collagen synthesis and degradation in rat skeletal muscle. Pflügers Archiv: European Journal of Physiology. 2002;**444**:59-72

**47**

2016;**22**:897-905

[158] Singh P, Carraher C, Schwarzbauer JE. Assembly of

*Skeletal Muscle Stem Cell Niche from Birth to Old Age DOI: http://dx.doi.org/10.5772/intechopen.93502*

Review of Cell and Developmental

[159] Bentzinger CF, Wang YX, von Maltzahn J, Soleimani VD, Yin H, Rudnicki MA. Fibronectin regulates Wnt7a signaling and satellite cell expansion. Cell Stem Cell. 2013;**12**:

[160] Yennek S, Burute M, Thery M, Tajbakhsh S. Cell adhesion geometry regulates non-random DNA segregation and asymmetric cell fates in mouse skeletal muscle stem cells. Cell Reports.

[162] Chazaud B, Sonnet C, Lafuste P, Bassez G, Rimaniol AC, Poron F, et al. Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growth. The Journal of Cell Biology. 2003;**163**:

[163] Saclier M, Yacoub-Youssef H, Mackey AL, Arnold L, Ardjoune H, Magnan M, et al. Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration.

Stem Cells. 2013;**31**:384-396

Embryologia. 1995;**24**:87-89

[164] Tidball JG. Nature reviews. Immunology. 2007;**17**:165-178

[165] Luque E, Pena J, Martin P, Jimena I, Vaamonde R. Capillary supply during development of individual regenerating muscle fibers. Anatomia, Histologia,

[166] Birbrair A, Zhang T, Wang ZM, Messi ML, Mintz A, Delbono O. Pericytes: multitasking cells in the regeneration of injured, diseased, and

Biology. 2010;**26**:397-419

75-87

2014;**7**:961-970

2013;**4**:1964

1133-1143

[161] Urciuolo A, Quarta M, Morbidoni V, Gattazzo F, Molon S, Grumati P, et al. Collagen VI regulates satellite cell self-renewal and muscle regeneration. Nature Communications.

McMahan UJ. Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites. The Journal of Cell Biology.

[151] Sanes JR, Marshall LM,

[152] Vracko R, Benditt EP. Basal lamina: The scaffold for orderly cell replacement: Observations on regeneration of injured skeletal muscle fibers and capillaries. The Journal of Cell Biology. 1972;**55**:406-419

[153] Webster MT, Manor U, Lippincott-Schwartz J, Fan CM. Intravital imaging reveals ghost fibers as architectural units guiding myogenic progenitors during regeneration. Cell

Stem Cell. 2016;**18**:243-252

2014;**141**:1184-1196

[154] Tidball JG, Dorshkind K,

Wehling-Henricks M. Shared signaling systems in myeloid cell-mediated muscle regeneration. Development.

[155] Tidball JG, Villalta SA. Regulatory interactions between muscle and the immune system during muscle regeneration. American journal of physiology. Regulatory, Integrative and Comparative Physiology. 2010;**298**:R1173-R1187

[156] Pannérec A, Marazzi G, Sassoon D. Stem cells in the hood: The skeletal muscle niche. Trends in Molecular Medicine. 2012;**18**:599-606. DOI: 10.1016/j.molmed.2012.07.004

[157] Lukjanenko L, Jung MJ, Hegde N, Perruisseau-Carrier C, Migliavacca E, Rozo M, et al. Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice. Nature Medicine.

fibronectin extracellular matrix. Annual

1978;**78**:176-198

*Skeletal Muscle Stem Cell Niche from Birth to Old Age DOI: http://dx.doi.org/10.5772/intechopen.93502*

[151] Sanes JR, Marshall LM, McMahan UJ. Reinnervation of muscle fiber basal lamina after removal of myofibers. Differentiation of regenerating axons at original synaptic sites. The Journal of Cell Biology. 1978;**78**:176-198

*Background and Management of Muscular Atrophy*

[143] Lepper C et al. An absolute requirement for Pax7-positive satellite cells in acute injury-induced skeletal muscle regeneration. Development.

[144] Hardy D, Besnard A, Latil M, Jouvion G, Briand D, Thepenier C, et al. Comparative study of injury models for studying muscle regeneration in mice.

PLoS One. 2016;**11**:e0147198

[145] Lukjanenko L, Brachat S, Pierrel E, Lach-Trifilieff E, Feige JN. Genomic profiling reveals that transient adipogenic activation is a hallmark of mouse models of skeletal muscle regeneration. PLoS One.

[146] Bischoff R. Interaction between satellite cells and skeletal muscle fibers. Development. 1990;**109**:943-952

Gallardo TD, Richardson JA, Garry DJ. Transcriptional profiling and regulation of the extracellular matrix during muscle regeneration. Physiological Genomics.

Dehaupas M, Lachkar S, Fournier JG, Verdiere-Sahuque M, et al. Expression of Matrix Metalloproteinases 2 and 9 in Regenerating Skeletal Muscle: A Study in Experimentally Injured and mdxMuscles. Developmental Biology.

[149] Caldwell CJ, Mattey DL, Weller RO. Role of the basement membrane in the regeneration of skeletal muscle. Neuropathology and Applied Neurobiology. 1990;**16**:225-238

[150] Koskinen SO, Ahtikoski AM, Komulainen J, Hesselink MK, Drost MR, Takala TE. Short-term effects of forced eccentric contractions on collagen synthesis and degradation in rat skeletal muscle. Pflügers Archiv: European Journal of Physiology. 2002;**444**:59-72

[147] Goetsch SC, Hawke TJ,

[148] Kherif S, Lafuma C,

2011;**138**:3639-3646

2013;**8**:e71084

2003;**14**:261-271

1999;**205**:158-170

function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell.

[134] Collins CA et al. Stem cell

[135] Gussoni E et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature.

[136] Benchaouir R et al. Restoration of human dystrophin following transplantation of exon-skippingengineered DMD patient stem cells into dystrophic mice. Cell Stem Cell.

[137] Sampaolesi M et al. Cell therapy of alpha-sarcoglycan null dystrophic mice through intra-arterial delivery of mesoangioblasts. Science.

[138] Sampaolesi M et al. Mesoangioblast

function in dystrophic dogs. Nature.

[139] Torrente Y. Human circulating AC133+ stem cells restore dystrophin expression and ameliorate function in dystrophic skeletal muscle. Journal of Clinical Investigation. 2004;**114**:182-195

[140] Dellavalle A et al. Pericytes resident in postnatal skeletal muscle differentiate into muscle fibres and generate satellite cells. Nature Communications. 2011;**2**:499

[141] Arnold L et al. Inflammatory

[142] Sambasivan R et al. Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration. Development. 2011;**138**:3647-3656

monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. The Journal of Experimental Medicine.

2007;**204**:1057-1069

stem cells ameliorate muscle

2005;**122**:289-301

1999;**401**:390-394

2007;**1**:646-657

2003;**301**:487-492

2006;**444**:574-579

**46**

[152] Vracko R, Benditt EP. Basal lamina: The scaffold for orderly cell replacement: Observations on regeneration of injured skeletal muscle fibers and capillaries. The Journal of Cell Biology. 1972;**55**:406-419

[153] Webster MT, Manor U, Lippincott-Schwartz J, Fan CM. Intravital imaging reveals ghost fibers as architectural units guiding myogenic progenitors during regeneration. Cell Stem Cell. 2016;**18**:243-252

[154] Tidball JG, Dorshkind K, Wehling-Henricks M. Shared signaling systems in myeloid cell-mediated muscle regeneration. Development. 2014;**141**:1184-1196

[155] Tidball JG, Villalta SA. Regulatory interactions between muscle and the immune system during muscle regeneration. American journal of physiology. Regulatory, Integrative and Comparative Physiology. 2010;**298**:R1173-R1187

[156] Pannérec A, Marazzi G, Sassoon D. Stem cells in the hood: The skeletal muscle niche. Trends in Molecular Medicine. 2012;**18**:599-606. DOI: 10.1016/j.molmed.2012.07.004

[157] Lukjanenko L, Jung MJ, Hegde N, Perruisseau-Carrier C, Migliavacca E, Rozo M, et al. Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice. Nature Medicine. 2016;**22**:897-905

[158] Singh P, Carraher C, Schwarzbauer JE. Assembly of fibronectin extracellular matrix. Annual Review of Cell and Developmental Biology. 2010;**26**:397-419

[159] Bentzinger CF, Wang YX, von Maltzahn J, Soleimani VD, Yin H, Rudnicki MA. Fibronectin regulates Wnt7a signaling and satellite cell expansion. Cell Stem Cell. 2013;**12**: 75-87

[160] Yennek S, Burute M, Thery M, Tajbakhsh S. Cell adhesion geometry regulates non-random DNA segregation and asymmetric cell fates in mouse skeletal muscle stem cells. Cell Reports. 2014;**7**:961-970

[161] Urciuolo A, Quarta M, Morbidoni V, Gattazzo F, Molon S, Grumati P, et al. Collagen VI regulates satellite cell self-renewal and muscle regeneration. Nature Communications. 2013;**4**:1964

[162] Chazaud B, Sonnet C, Lafuste P, Bassez G, Rimaniol AC, Poron F, et al. Satellite cells attract monocytes and use macrophages as a support to escape apoptosis and enhance muscle growth. The Journal of Cell Biology. 2003;**163**: 1133-1143

[163] Saclier M, Yacoub-Youssef H, Mackey AL, Arnold L, Ardjoune H, Magnan M, et al. Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration. Stem Cells. 2013;**31**:384-396

[164] Tidball JG. Nature reviews. Immunology. 2007;**17**:165-178

[165] Luque E, Pena J, Martin P, Jimena I, Vaamonde R. Capillary supply during development of individual regenerating muscle fibers. Anatomia, Histologia, Embryologia. 1995;**24**:87-89

[166] Birbrair A, Zhang T, Wang ZM, Messi ML, Mintz A, Delbono O. Pericytes: multitasking cells in the regeneration of injured, diseased, and aged skeletal muscle. Frontiers in Aging Neuroscience. 2014;**6**:245

[167] Deng B, Wehling-Henricks M, Villalta SA, Wang Y, Tidball JG. IL-10 triggers changes in macrophage phenotype that promote muscle growth and regeneration. Journal of Immunology. 2012;**189**:3669-3680

[168] Watkins SC, Cullen MJ. A quantitative study of myonuclear and satellite cell nuclear size in Duchenne's muscular dystrophy, polymyositis and normal human skeletal muscle. The Anatomical Record. 1988;**222**:6-11

[169] Sacco A et al. Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice. Cell. 2010;**143**:1059-1071. A report introducing the dystrophin/Tert1 deficient mouse as a better model that more closely recapitulates the human disorder DMD, and providing evidence that stem cell depletion exacerbates DMD symptoms

[170] Sahenk Z, Mendell JR. The muscular dystrophies: Distinct pathogenic mechanisms invite novel therapeutic approaches. Current Rheumatology Reports. 2011;**13**:199-207

[171] Rahimov F, Kunkel LM. The cell biology of disease: Cellular and molecular mechanisms underlying muscular dystrophy. The Journal of Cell Biology. 2013;**201**:499-510

[172] Tidball JG. Inflammatory processes in muscle injury and repair. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2005;**288**:R345-R353

[173] Serrano AL, Munoz-Canoves P. Fibrosis development in early-onset muscular dystrophies: Mechanisms and translational implications. Seminars in Cell & Developmental Biology. 2017;**64**:181-190

[174] Dadgar S, Wang Z, Johnston H, Kesari A, Nagaraju K, Chen YW, et al. Asynchronous remodeling is a driver of failed regeneration in Duchenne muscular dystrophy. The Journal of Cell Biology. 2014;**207**:139-158

[175] Peltonen L, Myllyla R, Tolonen U, Myllyla VV. Changes in collagen metabolism in diseased muscle: II. Immunohistochemical studies. Archives of Neurology. 1982;**39**:756-759

[176] Myllyla R, Myllyla VV, Tolonen U, Kivirikko KI. Changes in collagen metabolism in diseased muscle: I. Biochemical studies. Archives of Neurology. 1982;**39**:752-755

[177] Alvarez K, Fadic R, Brandan E. Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy. Journal of Cellular Biochemistry. 2002;**85**:703-713

[178] Caceres S, Cuellar C, Casar JC, Garrido J, Schaefer L, Kresse H, et al. Synthesis of proteoglycans is augmented in dystrophic mdx mouse skeletal muscle. European Journal of Cell Biology. 2000;**79**:173-181

[179] Alameddine HS, Morgan JE. Matrix metalloproteinases and tissue inhibitor of metalloproteinases in inflammation and fibrosis of skeletal muscles. Journal of Neuromuscular Diseases. 2016;**3**:455-473

[180] Fukushima K, Nakamura A, Ueda H, Yuasa K, Yoshida K, Takeda S, et al. Activation and localization of matrix metalloproteinase-2 and-9 in the skeletal muscle of the muscular dystrophy dog (CXMD J). BMC Musculoskeletal Disorders. 2007;**8**:54

[181] Sun GL, Zhao S, Li P, Jiang HK. Expression of tissue inhibitor of metalloproteinase-1 in progression

**49**

*Skeletal Muscle Stem Cell Niche from Birth to Old Age DOI: http://dx.doi.org/10.5772/intechopen.93502*

mouse muscle. Biochemical Society

[190] Okinaga T, Mohri I, Fujimura H, Imai K, Ono J, Urade Y, et al. Induction of hematopoietic prostaglandin D synthase in hyalinated necrotic muscle fibers: Its implication in grouped necrosis. Acta Neuropathologica.

Transactions. 1991;**19**:177S

2002;**104**:377-384

2003;**105**:217-224

2003;**17**:386-396

2011;**20**:790-805

[193] Villalta SA, Rinaldi C,

Human Molecular Genetics.

[194] Aragno M, Mastrocola R,

Diabetes. 2004;**53**:1082-1088

Medicine. 2011;**51**:993-999

Catalano MG, Brignardello E, Danni O, Boccuzzi G. Oxidative stress impairs skeletal muscle repair in diabetic rats.

[195] Henriksen EJ, Diamond-Stanic MK, Marchionne EM. Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radical Biology &

Deng B, Liu G, Fedor B, Tidball JG. Interleukin-10 reduces the pathology of mdx muscular dystrophy by deactivating M1 macrophages and modulating macrophage phenotype.

[191] Kuru S, Inukai A, Kato T, Liang Y, Kimura S, Sobue G.

Expression of tumor necrosis factor-α in regenerating muscle fibers in inflammatory and non-inflammatory myopathies. Acta Neuropathologica.

[192] Kumar A, Boriek AM. Mechanical stress activates the nuclear factor-kappa B pathway in skeletal muscle fibers: A possible role in Duchenne muscular dystrophy. The FASEB Journal.

[189] Nakagawa T, Takeuchi A, Kakiuchi R, Lee T, Yagi M, Awano H, et al. A prostaglandin D2 metabolite is elevated in the urine of Duchenne muscular dystrophy patients and increases further from 8 years old. Clinica Chimica Acta. 2013;**423**:10-14

muscular dystrophy. Neuroscience

Landeghem F, Stoltenburg-Didinger G, et al. Increased mRNA expression of tissue inhibitors of metalloproteinase-1

[183] Holland A, Murphy S, Dowling P, Ohlendieck K. Pathoproteomic profiling of the skeletal muscle matrisome in dystrophinopathy associated myofibrosis. Proteomics.

[184] Holland A, Dowling P, Meleady P, Henry M, Zweyer M, Mundegar RR, et al. Proteomics. Label-free mass spectrometric analysis of the mdx-4cv diaphragm identifies the matricellular protein periostin as a potential factor involved in dystrophinopathy-related

fibrosis. 2015;**15**:2318-2331

[186] Arecco N, Clarke CJ,

2016;**6**:24708

:e1010966

[185] Thakur R, Mishra DP. Matrix reloaded: CCN, tenascin and SIBLING group of matricellular proteins in orchestrating cancer hallmark capabilities. Pharmacology & Therapeutics. 2016;**168**:61-74

Jones FK, Simpson DM, Mason D, Beynon RJ, et al. Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation. Scientific Reports.

[187] Villalta SA, Rosenberg AS, Bluestone JA. The immune system in Duchenne muscular dystrophy: Friend

[188] McArdle A, Foxley A, Edwards RH, Jackson MJ. Prostaglandin metabolism

or foe. Rare Diseases. 2015;**3**

in dystrophin-deficient MDX

[182] von Moers A, Zwirner A, Reinhold A, Bruckmann O, van

and-2 in Duchenne muscular dystrophy. Acta Neuropathologica.

2005;**109**:285-293

2016;**16**:345-366

Bulletin. 2006;**22**:85-90

*Skeletal Muscle Stem Cell Niche from Birth to Old Age DOI: http://dx.doi.org/10.5772/intechopen.93502*

muscular dystrophy. Neuroscience Bulletin. 2006;**22**:85-90

*Background and Management of Muscular Atrophy*

aged skeletal muscle. Frontiers in Aging

[174] Dadgar S, Wang Z, Johnston H, Kesari A, Nagaraju K, Chen YW, et al. Asynchronous remodeling is a driver of failed regeneration in Duchenne muscular dystrophy. The Journal of Cell

Biology. 2014;**207**:139-158

[175] Peltonen L, Myllyla R,

1982;**39**:756-759

Tolonen U, Myllyla VV. Changes in collagen metabolism in diseased muscle: II. Immunohistochemical studies. Archives of Neurology.

[176] Myllyla R, Myllyla VV, Tolonen U, Kivirikko KI. Changes in collagen metabolism in diseased muscle: I. Biochemical studies. Archives of Neurology. 1982;**39**:752-755

[177] Alvarez K, Fadic R, Brandan E. Augmented synthesis and differential

[178] Caceres S, Cuellar C, Casar JC, Garrido J, Schaefer L, Kresse H, et al. Synthesis of proteoglycans is augmented in dystrophic mdx mouse skeletal muscle. European Journal of Cell

[179] Alameddine HS, Morgan JE. Matrix metalloproteinases and tissue inhibitor of metalloproteinases in inflammation and fibrosis of skeletal muscles. Journal of Neuromuscular Diseases.

[180] Fukushima K, Nakamura A, Ueda H, Yuasa K, Yoshida K, Takeda S, et al. Activation and localization of matrix metalloproteinase-2 and-9 in the skeletal muscle of the muscular dystrophy dog (CXMD J). BMC Musculoskeletal Disorders. 2007;**8**:54

[181] Sun GL, Zhao S, Li P, Jiang HK. Expression of tissue inhibitor of metalloproteinase-1 in progression

localization of heparan sulfate proteoglycans in Duchenne muscular

dystrophy. Journal of Cellular Biochemistry. 2002;**85**:703-713

Biology. 2000;**79**:173-181

2016;**3**:455-473

[167] Deng B, Wehling-Henricks M, Villalta SA, Wang Y, Tidball JG. IL-10 triggers changes in macrophage phenotype that promote muscle growth and regeneration. Journal of Immunology. 2012;**189**:3669-3680

[168] Watkins SC, Cullen MJ. A quantitative study of myonuclear and satellite cell nuclear size in Duchenne's muscular dystrophy, polymyositis and normal human skeletal muscle. The Anatomical

[169] Sacco A et al. Short telomeres and stem cell exhaustion model Duchenne muscular dystrophy in mdx/mTR mice. Cell. 2010;**143**:1059-1071. A report introducing the dystrophin/Tert1 deficient mouse as a better model that more closely recapitulates the human disorder DMD, and providing evidence that stem cell depletion exacerbates

Record. 1988;**222**:6-11

DMD symptoms

[170] Sahenk Z, Mendell JR. The muscular dystrophies: Distinct pathogenic mechanisms invite novel therapeutic approaches. Current Rheumatology Reports. 2011;**13**:199-207

[171] Rahimov F, Kunkel LM. The cell biology of disease: Cellular and molecular mechanisms underlying muscular dystrophy. The Journal of Cell

[172] Tidball JG. Inflammatory processes in muscle injury and repair. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.

[173] Serrano AL, Munoz-Canoves P. Fibrosis development in early-onset muscular dystrophies: Mechanisms and translational implications. Seminars in Cell & Developmental Biology.

Biology. 2013;**201**:499-510

2005;**288**:R345-R353

2017;**64**:181-190

Neuroscience. 2014;**6**:245

**48**

[182] von Moers A, Zwirner A, Reinhold A, Bruckmann O, van Landeghem F, Stoltenburg-Didinger G, et al. Increased mRNA expression of tissue inhibitors of metalloproteinase-1 and-2 in Duchenne muscular dystrophy. Acta Neuropathologica. 2005;**109**:285-293

[183] Holland A, Murphy S, Dowling P, Ohlendieck K. Pathoproteomic profiling of the skeletal muscle matrisome in dystrophinopathy associated myofibrosis. Proteomics. 2016;**16**:345-366

[184] Holland A, Dowling P, Meleady P, Henry M, Zweyer M, Mundegar RR, et al. Proteomics. Label-free mass spectrometric analysis of the mdx-4cv diaphragm identifies the matricellular protein periostin as a potential factor involved in dystrophinopathy-related fibrosis. 2015;**15**:2318-2331

[185] Thakur R, Mishra DP. Matrix reloaded: CCN, tenascin and SIBLING group of matricellular proteins in orchestrating cancer hallmark capabilities. Pharmacology & Therapeutics. 2016;**168**:61-74

[186] Arecco N, Clarke CJ, Jones FK, Simpson DM, Mason D, Beynon RJ, et al. Elastase levels and activity are increased in dystrophic muscle and impair myoblast cell survival, proliferation and differentiation. Scientific Reports. 2016;**6**:24708

[187] Villalta SA, Rosenberg AS, Bluestone JA. The immune system in Duchenne muscular dystrophy: Friend or foe. Rare Diseases. 2015;**3** :e1010966

[188] McArdle A, Foxley A, Edwards RH, Jackson MJ. Prostaglandin metabolism in dystrophin-deficient MDX

mouse muscle. Biochemical Society Transactions. 1991;**19**:177S

[189] Nakagawa T, Takeuchi A, Kakiuchi R, Lee T, Yagi M, Awano H, et al. A prostaglandin D2 metabolite is elevated in the urine of Duchenne muscular dystrophy patients and increases further from 8 years old. Clinica Chimica Acta. 2013;**423**:10-14

[190] Okinaga T, Mohri I, Fujimura H, Imai K, Ono J, Urade Y, et al. Induction of hematopoietic prostaglandin D synthase in hyalinated necrotic muscle fibers: Its implication in grouped necrosis. Acta Neuropathologica. 2002;**104**:377-384

[191] Kuru S, Inukai A, Kato T, Liang Y, Kimura S, Sobue G. Expression of tumor necrosis factor-α in regenerating muscle fibers in inflammatory and non-inflammatory myopathies. Acta Neuropathologica. 2003;**105**:217-224

[192] Kumar A, Boriek AM. Mechanical stress activates the nuclear factor-kappa B pathway in skeletal muscle fibers: A possible role in Duchenne muscular dystrophy. The FASEB Journal. 2003;**17**:386-396

[193] Villalta SA, Rinaldi C, Deng B, Liu G, Fedor B, Tidball JG. Interleukin-10 reduces the pathology of mdx muscular dystrophy by deactivating M1 macrophages and modulating macrophage phenotype. Human Molecular Genetics. 2011;**20**:790-805

[194] Aragno M, Mastrocola R, Catalano MG, Brignardello E, Danni O, Boccuzzi G. Oxidative stress impairs skeletal muscle repair in diabetic rats. Diabetes. 2004;**53**:1082-1088

[195] Henriksen EJ, Diamond-Stanic MK, Marchionne EM. Oxidative stress and the etiology of insulin resistance and type 2 diabetes. Free Radical Biology & Medicine. 2011;**51**:993-999

[196] Jeong J, Conboy MJ, Conboy IM. Pharmacological inhibition of myostatin/TGF-β receptor/pSmad3 signaling rescues muscle regenerative responses in mouse model of type 1 diabetes. Acta Pharmacologica Sinica. 2013;**34**:1052-1060

[197] Krause MP, Al-Sajee D, D'Souza DM, Rebalka IA, Moradi J, Riddell MC, et al. Impaired macrophage and satellite cell infiltration occurs in a muscle-specific fashion following injury in diabetic skeletal muscle. PLoS One. 2013;**8**:e70971

[198] Nunan R, Harding KG, Martin P. Clinical challenges of chronic wounds: Searching for an optimal animal model to recapitulate their complexity. Disease Models & Mechanisms. 2014;**7**:1205-1213

[199] Berria R, Wang L, Richardson DK, Finlayson J, Belfort R, Pratipanawatr T, et al. Increased collagen content in insulin-resistant skeletal muscle. American journal of physiology. Endocrinology and Metabolism. 2006;**290**:E560-E565

[200] Hong EG, Ko HJ, Cho YR, Kim HJ, Ma Z, Yu TY, et al. Interleukin-10 prevents diet-induced insulin resistance by attenuating macrophage and cytokine response in skeletal muscle. Diabetes. 2009;**58**:2525-2535

[201] Richardson DK, Kashyap S, Bajaj M, Cusi K, Mandarino SJ, Finlayson J, et al. Lipid infusion decreases the expression of nuclear encoded mitochondrial genes and increases the expression of extracellular matrix genes in human skeletal muscle. The Journal of Biological Chemistry. 2005;**280**:10290-10297

[202] Watts R, McAinch AJ, Dixon JB, O'Brien PE, Cameron-Smith D. Increased Smad signaling and reduced MRF expression in skeletal muscle from obese subjects. Obesity (Silver Spring). 2013;**21**:525-528

[203] Chiu CY, Yang RS, Sheu ML, Chan DC, Yang TH, Tsai KS, et al. Advanced glycation end-products induce skeletal muscle atrophy and dysfunction in diabetic mice via a RAGE-mediated, AMPK-downregulated, Akt pathway. The Journal of Pathology. 2016;**238**:470-482

[204] Morley JE, Thomas DR, Wilson MM. Cachexia: Pathophysiology and clinical relevance. The American Journal of Clinical Nutrition. 2006;**83**:735-743

[205] Acharyya S, Butchbach ME, Sahenk Z, Wang H, Saji M, Carathers M, et al. Dystrophin glycoprotein complex dysfunction: A regulatory link between muscular dystrophy and cancer cachexia. Cancer Cell. 2005;**8**:421-432

[206] He WA, Berardi E, Cardillo VM, Acharyya S, Aulino P, Thomas-Ahner J, et al. NF-κB–mediated Pax7 dysregulation in the muscle microenvironment promotes cancer cachexia. The Journal of Clinical Investigation. 2013;**123**:4821-4835

[207] Niks EH, Aartsma-Rus A. Exon skipping: A first in class strategy for Duchenne muscular dystrophy. Expert Opinion on Biological Therapy. 2017;**17**: 225-236

[208] Bello L, Pegoraro E. Genetic diagnosis as a tool for personalized treatment of Duchenne muscular dystrophy. Acta Myologica. 2016;**35**:122-127

**51**

**Chapter 3**

*Eli Carmeli*

radicals, cytokines

**1. Introduction**

**1.1 The "unhappy triad"**

and obesity) and arthritis.

**Abstract**

Sarcopenia in Older Adults

age-related decline in muscle mass and strength.

Sarcopenia has become of great interest and focus of many studies since this phenomenon affects many people. Moreover, sarcopenia is associated with two more pandemic phenomena: frailty and obesity. These health-related conditions are increasing in western countries in general and in the older population in particular. Each of such health conditions relates to functional decline, yet the combination of two or three of them in one person severely affects quality of life and longevity. Aged individuals who are less physically active are more likely to develop sarcopenic obesity, and those who are obese with muscle weakness and inactive are disposed to become frail individuals. Hence, frailty and obesity overlap profoundly with the physical manifestations of sarcopenia of aging. These "unhappy" triads encompasses a wider range of geriatric decline that also includes cognitive, psychology and social deterioration associated with adverse outcomes. Nevertheless, this chapter focuses only on sarcopenia and will review the pathophysiological background of

**Keywords:** sarcopenia, elderly, strength, muscle mass, physical performance,

The end of the last century and the beginning of the first two decades of the present century were characterized by the rise of three medical or health pandemic phenomena, each of which has a serious impact on public health and especially among older people. These three conditions are frailty, sarcopenia, and obesity. When sarcopenia or frailty is also accompanied by obesity, a sarcopenic/frail-obese phenotype is established [1]. Moreover, the presence of these "unhappy triads" of health conditions, in one person, poses a significant threat to one's quality of life and longevity. The prevalence of each of such conditions (i.e., frailty, sarcopenia, and obesity) is widely estimated within different countries; however, with no one single best outcome measure for these diagnoses, there is highly wide range of

A "cycle of sarcopenia" may be created in which in the presence of one or two factors such as frailty and or obesity, sarcopenia status is likely to continue to deteriorate unless there is outside intervention. It is extremely difficult to overcome this "unhappy triad" when the affected people do not have the resources necessary to get out of muscle weakness and fatigue, such as lower cardiac function (myocardial infraction, angina, chronic heart failure, metabolic state (hypertension, diabetes,

manifestation and diagnoses in each of these health phenomena [2].
