Muscle satellite cells are believed to represent a committed stem cell population that is responsible for the postnatal growth and regeneration of skeletal muscle. However, the observation that cultured myoblasts differentiate 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 satellite cell-derived primary myoblasts, expressing myogenic markers such as MyoD, Myf5, Pax7 and desmin, differentiated only into osteocytes or adipocytes following treatment with BMPs or adipogenic inducers, respectively However, satellite cells on isolated muscle fibers cultured in Matrigel readily differentiated into myocytes as well as osteogenic and adipogenic lineages, whereas primary myoblasts did not. Satellite cell-derived primary myoblasts isolated from mice lacking the myogenic transcription factor MyoD (MyoD-/-) 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 relative to wild type cells. Unexpectedly, the osteogenic or adipogenic differentiation potential of MyoD-/- primary myoblasts did not increase compared to wild-type cells. Taken together, these results strongly suggest that muscle satellite cells possess multipotential mesenchymal stem cell activity and are capable of forming osteocytes and adipocytes as well as myocytes.