**9. miRNA regulation in osteoblast differentiation**

Differentiation of the osteoblast cells is an essential facet for the development of the adult skeleton. Most importantly, miRNAs have great potential to act against


#### **Table 2.**

*Role of miRNAs in the osteogenic differentiation by acting on various components in the bone signaling pathways.*

**219**

*MicroRNAs as Next Generation Therapeutics in Osteoporosis*

**10. miRNA regulation in bone resorption**

or in favor of the genes that are involved in the process of bone differentiation (**Table 2**). miRNA usually targets genes that are participating in the osteo-signaling

miRNAs not only regulates the osteoblastogenesis but also sustains the bone disruptive processes by acting on the genes or proteins partaking in the signaling pathways that are functional inside the osteoclast (**Table 3**). Understanding the miRNA mediated regulation of osteoclastic differentiation will highlight the mechanism behind the differentiation process for the osteoclasts in the bone [84]. Initiating signal (binding of RANKL to the receptors) stimulates various downstream pathways (PI3K, NFK-β, MAPK) that on activation of distinct transcription

**miRNA Target Effect Reference** miR-503 RANK Represses osteoclast formation in PBMC [79]

bone mineral density

Decreases osteoclast formation and controls

[80]

[81]

Both the overexpression and inhibition of miRNA can be exploited for the development of potential therapeutics. miRNA sponges, Anti-miRNAs and miRNA masks are few strategies for the suppression of intracellular miRNAs. Anti-miRNAs are the miRNA inhibitors which are constructed as complementary to miRNA sequences. They prohibit the binding of miRNAs to the mRNA targets and relieve the gene suppression phenotype. Anti-miRNAs are specific in action as they are custom synthesized as entirely complementary to naturally existing miRNAs [85]. While, delivery of miRNA is achieved with the help of miRNA mimics, that imitates the sequence and action of miRNAs in the in vitro or in vivo systems. Furthermore, miRNA work as both oncogenes and tumor suppressors, thus contributes to the pathogenesis of several cancerous diseases. MiR-21 founds to be highly upregulated during breast tumors while the levels of miR-196a are significantly increased in the pancreatic cancers [86, 87]. Role of miRNAs is also evidently noticed in many other diseases viz. liver diseases, cardiac dysfunctions, renal failures, neurodegenerative diseases, etc. [88].

factors (c-Fos, NFATc1, PU.1) control the osteoclast differentiation [84].

miR-141 Calcr Suppresses osteoclast differentiation, increases

*Representation of a few examples where miRNAs have played a vital role in the bone resorption.*

osteoporosis

miR-124 Nfatc1 Represses osteoclast differentiation [82] miR-155 MITF Suppression of the osteoclastogenesis [83] miR-21 FasL PDCD4 Hinders the apoptosis of osteoclasts [84] miR-148a MAFB Encourages osteoclasts development [84] miR-125a TRAF6 Restricts the formation of osteoclasts [84] *PBMC, peripheral blood mononuclear cells; Calcr, calcitonin receptor; CXCL12, C-X-C motif chemokine 12; MITF, microphthalmia-associated transcription factor; PDCD4, programmed cell death protein 4; MAFB, MAF BZIP* 

*DOI: http://dx.doi.org/10.5772/intechopen.91223*

resulting in the bone differentiation.

**11. miRNAs as therapeutics**

*transcription factor B.*

**Table 3.**

miR-29a RANKL and

CXCL12

or in favor of the genes that are involved in the process of bone differentiation (**Table 2**). miRNA usually targets genes that are participating in the osteo-signaling resulting in the bone differentiation.
