Osteogenic protein‐1 (OP‐1, BMP‐7) induces osteoblastic cell differentiation of the pluripotent mesenchymal cell line C2C12

The effects of Osteogenic Protein‐1 (OP‐1, BMP‐7) on the differentiation of the pluripotent mesenchymal cell line, C2C12, were examined. OP‐1 at 50 ng/ml partially inhibited myotube formation in C2C12 cells, while OP‐1 at 200 ng/ml completely inhibited myotube formation and induced the formation of cells displaying osteoblastic morphology. High concentrations of OP‐1 elevated the alkaline phosphatase (AP) activity dramatically, both as a function of time and OP‐1 concentration. Osteocalcin (OC) mRNA expression was detected as early as 8 days in OP‐1‐treated cultures and subsequently increased considerably. Expression of bone sialoprotein (BSP) mRNA was low in control cultures and stimulated by OP‐1. Collagen type I mRNA expression was enhanced by OP‐1 during the early days in culture, but gradually decreased thereafter. MyoD mRNA expression, high in control cultures, was suppressed by OP‐1 in a dose‐ and time‐dependent manner. OP‐1 enhanced ActR‐I mRNA expression and significantly elevated the mRNA expressions of BMP‐1, BMP‐4, BMP‐5, GDF‐6, and GDF‐8. The present results indicate that OP‐1 is a potent inducer of C2C12 differentiation into osteoblastic cells. J. Cell. Biochem. 87: 292–304, 2002. © 2002 Wiley‐Liss, Inc.