Extracellular matrix-driven congenital muscular dystrophies

• Published in: Matrix biology Vol. 71-72; pp. 188 - 204
• Main Authors: Mohassel, Payam, Foley, A. Reghan, Bönnemann, Carsten G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2018; Elsevier Science Ltd
• Subjects: Animals; Basement Membrane - metabolism; Collagen Type VI - genetics; Collagen Type VI - metabolism; Congenital diseases; Extracellular matrix; Extracellular Matrix - genetics; Extracellular Matrix - metabolism; Growth factors; Humans; Inflammation; Laminin - genetics; Laminin - metabolism; Membrane proteins; Muscle, Skeletal - metabolism; Muscular Dystrophies - congenital; Muscular Dystrophies - genetics; Muscular Dystrophies - metabolism; Muscular dystrophy; Mutation; Proteins; Skeletal muscle; Stem cells; Therapeutic applications
• ISSN: 0945-053X; 1569-1802; 1569-1802
• DOI: 10.1016/j.matbio.2018.06.005

Skeletal muscle function relies on the myofibrillar apparatus inside myofibers as well as an intact extracellular matrix surrounding each myofiber. Muscle extracellular matrix (ECM) plays several roles including but not limited to force transmission, regulation of growth factors and inflammatory responses, and influencing muscle stem cell (i.e. satellite cell) proliferation and differentiation. In most myopathies, muscle ECM undergoes remodeling and fibrotic changes that may be maladaptive for normal muscle function and recovery. In addition, mutations in skeletal muscle ECM and basement proteins can cause muscle disease. In this review, we summarize the clinical features of two of the most common congenital muscular dystrophies, COL6-related dystrophies and LAMA2-related dystrophies, which are caused by mutations in muscle ECM and basement membrane proteins. The study of clinical features of these diseases has helped to inform basic research and understanding of the biology of muscle ECM. In return, basic studies of muscle ECM have provided the conceptual framework to develop therapeutic interventions for these and other similar disorders of muscle. •COL6-related dystrophies and LAMA2-related dystrophies are prototypical diseases of muscle extracellular matrix.•Early-onset and progressive large joint contractures are prominent in these dystrophies.•Study of extramuscular features of these diseases, including joint contractures, should be included in future studies.•Non-invasive ventilatory support is an essential part of clinical management of most patients with COL6-RDs and LAMA2-RDs.•Delineation of the ECM role in disease mechanism has primed several therapeutic strategies for these disorders.