**Acknowledgements**

dermatopontin, prolargin and periostin [83]. Especially interesting was the proteomic identi‐ fication of dermatopontin and periostin [83,128,129]. Dermatopontin, also named tyrosine-rich acidic matrix protein TRAMP [130], is involved in matrix assembly and cell–matrix interactions [17] via interactions with decorin, TGF-β and fibronectin [131]. High levels of dermatopontin in the dystrophic *mdx* diaphragm most likely reflect an increased demand for collagen matrix organization within Dp427-deficient fibres [128]. Periostin is a crucial matricellular protein of 93 kDa [18] that is involved in the regulation of the biomechanical properties of connective tissues and collagen fibrillogenesis [132]. Normally periostin is only temporally expressed in the muscle ECM during cellular differentiation and regeneration processes [133], making its drastic up-regulation a characteristic feature of dystrophic muscles [83,86]. Of diagnostic and therapeutic importance is the fact that muscle biopsies from Duchenne patients exhibit an elevated concentration of periostin and that the deletion of periostin clearly reduces dystrophic symptoms and myofibrosis in mice by modulating the TGF-β pathway [134]. Interestingly, laminin-deficient muscular dystrophy also shows dysregulation of matricellular proteins as an early pathophysiological feature [120,135]. Therefore altered levels of periostin and related matricellular proteins are good biomarker candidates for the characterization of myofibrosis in relation to inherited muscular dystrophies [136]. Although the natural aging process is also associated with increased collagen levels [116], which were also shown by proteomics [137], the collagen accumulation is much less pronounced in senescent muscles as compared to

80 Composition and Function of the Extracellular Matrix in the Human Body

In conclusion, a dynamic balance exists within the ECM system from skeletal muscles. Highly regulated cycles of protein deposition, accumulation, remodelling and degradation occur in response to development, fibre transformation, neuromuscular loading, mechanical unload‐ ing, disease processes or aging. The main components of the ECM are represented by collagen fibres, non-fibrillar collagens, matricellular proteins, proteoglycans, matrix metalloproteinas‐ es, signalling molecules and adhesion complexes. The muscle ECM forms a structural scaffold that plays a central role in the maintenance of the physical structure of motor units and provides the framework for force transmission. The ECM is also involved in signalling cascades and adhesion processes at the sarcolemma–matrix interface. The systematic mass spectrometry-based proteomic analysis of the muscle ECM has established an enormous complexity and interconnectivity of matrix proteins and confirmed the dynamic nature of collagen networks and its associated proteoglycans in health and disease. Swift adaptations or alterations in the arrangement of the ECM have been established to occur during myogen‐ esis, fibre regeneration, increased neuromuscular activity or pathological muscle wasting. Hence, concentration changes in ECM proteins are useful indicators for studying basic cell biological or pathophysiological processes in skeletal muscles. In the future, distinct ECM molecules may be useful for designing improved diagnostic, prognostic or therapy-monitoring

muscular dystrophy.

**6. Conclusions**

approaches to study neuromuscular alterations.

Research in the author's laboratory was supported by project grants from the Deutsche Duchenne Stiftung *aktion benni & co e.V.*, Muscular Dystrophy Ireland and the Hume Scholar‐ ship programme of Maynooth University, as well as the Irish Higher Education Authority (HEA). The Programme for Research in Third Level Institutions PRTLI Cycle 5 is co-funded by the Irish Government and the European Union under Ireland's EU Structural Funds Programme 2007-2013. We thank Prof. Dieter Swandulla (University of Bonn), Prof. Heinrich Brinkmeier (University of Greifswald) and Dr. Paula Meleady (Dublin City University) for their continued support of our studies into the mechanisms of muscle fibrosis.
