Chapter 13 Complexity of Extracellular Matrix and Skeletal Muscle Regeneration

Skeletal muscle regeneration occurs by the activation, proliferation and fusion of muscle precursor cells (myoblasts) that usually lie in a satellite cell position on the surface of the sarcolemma beneath the external lamina (basement membrane) of myofibres. Thus these myoblasts (satellite cells), as is the whole surface of the myfibre and the neuromuscular junctions (NMJ), are in intimate contact with the specialized components of the extracellular matrix (ECM) that compose the basement membrane (often referred to as basal lamina). Interactions between the surface of myofibres and the basement membrane ensure the effective transfer of the contractile force (generated in the sarcomeres) laterally across the cell surface to the ECM for full force generation. Beyond the intimate interactions of skeletal muscle cells with the basement membrane lies interstitial connective tissue that contains blood vessels, nerves and lymphatics. The ECM also contains a wealth of circulating and other proteins (Bortoluzzi et al., 2006). The importance of the ECM is often overlooked yet it is the environment of the cells (from myoblasts and myofibres to endothelium and nerves) that dictates what will occur. During development, myoblasts migrate through the ECM and proliferate to form new muscle fibres initially in the absence of a basement membrane. This contrasts with the situation in mature muscle where the myoblasts (derived mainly from satellite cells) lie beneath the basement membrane of myofibres. Most myofibre damage resulting from exercise/contraction-induced injury, muscle disease or muscle transplantation, does not severely disrupt the basement membrane, thus the myoblasts become activated, proliferate and fuse within this niche environment.