In postnatal muscle, skeletal muscle precursors (myoblasts) can be derived from satellite cells (reserve cells located on the surface of mature myofibers) or from cells lying beyond the myofiber, e.g., interstitial connective tissue or bone marrow. Both of these classes of cells may have stem cell properties. In addition, the heretical idea that post-mitotic myonuclei lying within mature myofibers might be able to re-form myoblasts or stem cells is examined and related to recent observations for similar post-mitotic cardiomyocytes. In adult hearts (which previously were not considered capable of repair), the role of replicating endogenous cardiomyocytes and the recruitment of other (stem) cells into cardiomyocytes for new cardiac muscle formation has recently attracted much attention. The relative contribution of these various sources of precursor cells in postnatal muscles and the factors that may enhance stem cell participation in the formation of new skeletal and cardiac muscle in vivo are the focus of this review. We concluded that, although many endogenous cell types can be converted to skeletal muscle, the contribution of non-myogenic cells to the formation of new postnatal skeletal muscle in vivo appears to be negligible. Whether the recruitment of such cells to the myogenic lineage can be significantly enhanced by specific inducers and the appropriate microenvironment is a current topic of intense interest. However, dermal fibroblasts appear promising as a realistic alternative source of exogenous myoblasts for transplantation purposes. For heart muscle, experiments showing the participation of bone marrow-derived stem cells and endothelial cells in the repair of damaged cardiac muscle are encouraging.

Necrosis of dystrophic myofibers in Duchenne muscular dystrophy and mdx mice results from defects in the subsarcolemmal protein dystrophin that cause membrane fragility and tears in the sarcolemma, and these lead to the destruction of the myofibers. The present study specifically tests whether overexpression of mIGF-1 in mdx/mIGF-1 transgenic mice reduces myofiber breakdown during the acute onset phase of dystrophy (at 21 days). The extent of muscle damage and Evans blue dye (EBD) staining of myofibers was quantitated histologically for mdx/mIGF-1 and their mdx littermates from 15 to 30 days of age. Overexpression of mIGF-1 strikingly reduced the extent of myofiber damage (histology and EBD staining) by up to 97% in tibialis anterior and quadriceps muscles at 21-22 days after birth. In the mdx diaphragm, the onset of muscle breakdown was earlier (by 15 days after birth) but no significant protective effect of IGF-1 was apparent within the first month of age in mdx/IGF-1 mice. These novel observations show that increased mIGF-1 within mdx myofibers specifically reduces the breakdown of dystrophic muscle during the acute onset of muscle degeneration. This mechanism of action can account for the long-term reduced severity of the dystropathology in mdx mice that overexpress mIGF-1 and provides promising opportunities for therapeutic strategies.

We compared the time course of myogenic events in vivo in regenerating whole muscle grafts in MyoD(−/−) and control BALB/c adult mice using immunohistochemistry and electron microscopy. Immunohistochemistry with antibodies to desmin and myosin revealed a striking delay by about 3 days in the formation of myotubes in MyoD(−/−) autografts compared with BALB/c mice. However, myotube formation was not prevented, and autografts in both strains appeared similar by 8 days. Electron microscopy confirmed myotube formation in 8- but not 5-day MyoD(−/−) grafts. This pattern was not influenced by cross-transplantation experiments between strains examined at 5 days. Antibodies to proliferating cell nuclear antigen demonstrated an elevated level of replication by MyoD(−/−) myoblasts in autografts, and replication was sustained for about 3 days compared with controls. These data indicate that the delay in the onset of differentiation and hence fusion is related to extended proliferation of the MyoD(−/−) myoblasts. Overall, although muscle regeneration was delayed it was not impaired in MyoD(−/−) mice in this model.

Skeletal muscle development and regeneration requires the fusion of myoblasts into multinucleated myotubes. Because the enzymatic proteolysis of a hyaluronan and versican-rich matrix by ADAMTS versicanases is required for developmental morphogenesis, we hypothesized that the clearance of versican may facilitate the fusion of myoblasts during myogenesis. Here, we used transgenic mice and an in vitro model of myoblast fusion, C2C12 cells, to determine a potential role for ADAMTS versicanases. Versican processing was observed during in vivo myogenesis at the time when myoblasts were fusing to form multinucleated myotubes. Relevant ADAMTS genes, chief among them Adamts5 and Adamts15, were expressed both in developing embryonic muscle and differentiating C2C12 cells. Reducing the levels of Adamts5 mRNA in vitro impaired myoblast fusion, which could be rescued with catalytically active but not the inactive forms of ADAMTS5 or ADAMTS15. The addition of inactive ADAMTS5, ADAMTS15, or full-length V1 versican effectively impaired myoblast fusion. Finally, the expansion of a hyaluronan and versican-rich matrix was observed upon reducing the levels of Adamts5 mRNA in myoblasts. These data indicate that these ADAMTS proteinases contribute to the formation of multinucleated myotubes such as is necessary for both skeletal muscle development and during regeneration, by remodeling a versican-rich pericellular matrix of myoblasts. Our study identifies a possible pathway to target for the improvement of myogenesis in a plethora of diseases including cancer cachexia, sarcopenia, and muscular dystrophy.

This study aimed to quantify the effect of muscle, ageing and cooking temperature on the texture, cooking loss and shrinkage of cooked beef. Cuboids from unaged (1 day post mortem) and aged (14 days post mortem) semitendinosus, biceps femoris and psoas major muscles, from both sides of five beef carcasses, were cooked at four different cooking temperatures (50, 60, 70 and 80 °C) for 30 min. and their Warner–Bratzler shear force (WBSF), cooking loss and shrinkage (longitudinal and transverse) were quantified. The WBSF was reduced by ageing in the muscles at the specific cooking temperatures: psoas major (cooked at 50, 60 and 80 °C), semitendinosus (70 and 80 °C) and biceps femoris (80 °C). The cooking loss was 3% greater in aged compared to unaged muscles. The longitudinal shrinkage was greatest in psoas major at 80 °C amongst the muscle types and it was reduced by ageing in psoas major (70 and 80 °C) and biceps femoris (80 °C). The transverse shrinkage was reduced by ageing only in biceps femoris, across all temperatures; and the diameter of homogenized fibre fragments from semitendinosus and biceps femoris was reduced more by cooking at 50 °C in unaged compared to aged condition. WBSF was related to transverse shrinkage, and cooking loss was related to longitudinal shrinkage. The effect of muscle type on the physical changes occurring during cooking of beef is dependent on ageing and cooking temperature.