Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation

Muscle satellite cells are believed to represent a committed stem cell popu lation that is responsible for the postnatal growth and regeneration of ske letal muscle. However, the observation that cultured myoblasts differentiat e into osteocytes or adipocytes following treatment with bone morphogenetic proteins (BMPs) or adipogenic inducers, respectively, suggests some degree of plasticity within the mesenchymal lineage. To further investigate this phenomenon, we explore the osteogenic and adipogenic potential of satellite cells isolated from adult mice. Our experiments clearly demonstrate that s atellite cell-derived primary myoblasts, expressing myogenic markers such a s MyoD, Myf5, Pax7 and desmin, differentiated only into osteocytes or adipo cytes following treatment with BMPs or adipogenic inducers, respectively. H owever, satellite cells on isolated muscle fibers cultured in Matrigel read ily differentiated into myocytes as well as osteogenic and adipogenic linea ges, whereas primary myoblasts did not. Satellite cell-derived primary myob lasts isolated from mice lacking the myogenic transcription factor MyoD (My oD-/-) differentiate into myocytes poorly in vivo and in vitro (Megeney et al., Genes Dev. 1996; Sabourin et. al, J. Cell Biol., 1999). Therefore, we tested whether MyoD-/- primary myoblasts display increased plasticity relat ive to wild type cells. Unexpectedly, the osteogenic or adipogenic differen tiation potential of MyoD-/- primary myoblasts did not increase compared to wild-type cells. Taken together, these results strongly suggest that muscl e satellite cells possess multipotential mesenchymal stem cell activity and are capable of forming osteocytes and adipocytes as well as myocytes.