Abstract
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.
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