Regulation of differentiation pathway of skeletal mesenchymal cells in cell lines by transforming growth factor-beta superfamily.

The skeletal mesenchymal cells including osteoblasts, chondrocytes, muscle cells and adipocytes are believed to be derived from the common mesenchymal progenitors. Using various cell lines, multipotential mesenchymal progenitors capable of differentiating into these cell lineages have been demonstrated to be present in the skeletal tissues. The developmental potential of the progenitors becomes more restricted according to their maturation stages in the specialized cell lineages. Among the various growth factors, bone morphogenetic protein (BMP), which belongs to the transforming growth factor-beta (TGF-beta) superfamily, plays an important role in the regulation of the differentiation pathway of these mesenchymal cells. BMP-2 induces the undifferentiated mesenchymal progenitors to differentiate into osteoblasts, chondrocytes and adipocytes. BMP-2 also stimulates the committed osteo-chondroprogenitors to differentiate into more mature cell types, but inhibits myogenic cells to differentiate into myotubes. BMP-2 converts the differentiation pathway of C2C12 myoblasts into the osteogenic lineage associating with decreases in the expression levels of the muscle specific regulatory factors such as myogenin and MyoD. TGF-beta inhibits myotube formation in myogenic cell lines, but does not stimulate osteoblast differentiation. The TGF-beta superfamily plays important roles in the differentiation process of the skeletal mesenchymal cells.