Molecular mechanisms of skeletal muscle development, regeneration, and osteogenic conversion

Both skeletal muscle and bone are of mesodermal origin and derived from somites during embryonic development. Somites differentiate into the dorsal dermomyotome and the ventral sclerotome, which give rise to skeletal muscle and bone, respectively. Extracellular signaling molecules, such as Wnt and Shh, secreted from the surrounding environment, determine the developmental fate of skeletal muscle. Dermomyotome cells are specified as trunk muscle progenitor cells by transcription factor networks involving Pax3. These progenitor cells delaminate and migrate to form the myotome, where they are determined as myoblasts that differentiate into myotubes or myofibers. The MyoD family of transcription factors plays pivotal roles in myogenic determination and differentiation. Adult skeletal muscle regenerates upon exercise, muscle injury, or degeneration. Satellite cells are muscle-resident stem cells and play essential roles in muscle growth and regeneration. Muscle regeneration recapitulates the process of muscle development in many aspects. In certain muscle diseases, ectopic calcification or heterotopic ossification, as well as fibrosis and adipogenesis, occurs in skeletal muscle. Muscle-resident mesenchymal progenitor cells, which may be derived from vascular endothelial cells, are responsible for the ectopic osteogenesis, fibrogenesis, and adipogenesis. The small GTPase M-Ras is likely to participate in the ectopic calcification and ossification, as well as in osteogenesis during development. This article is part of a Special Issue entitled "Muscle Bone Interactions".