Differential effects of osteogenic protein-1 (BMP-7) on gene expression of BMP and GDF family members during differentiation of the mouse MC615 chondrocyte cells.

The mRNA expression patterns of several bone morphogenetic proteins (BMPs) and growth differentiation factors (GDFs) in long-term cultures of the clonal mouse chondrocyte cell line MC615 were examined. Distinct spatial and temporal patterns of expression of BMPs and GDFs were observed. The temporal orders of expression were correlated with those of several biochemical markers characteristic of chondrocytic cell differentiation. BMP-1, -2, -5, and -6 mRNA expression increased throughout the chondrogenic process and BMP-4 mRNA expression was not changed. GDF-1 and -3 mRNA expression increased throughout the chondrogenic process, and GDF-5, -6, -8, and -9 mRNA expressions were not changed. Effects of osteogenic protein-1 (OP-1, BMP-7) on the expression patterns of several other members of the BMP family and of the GDF family were also examined. OP-1 downregulated the BMP-1, -4, -5, and -6 mRNA expression by a maximal 3-, 5-, 2.5-, and 3-fold, respectively. The BMP-2 mRNA expression was not changed significantly by a low concentration of OP-1, but was increased at 200 ng/ml at day 7 of treatment. In contrast to the BMPs, OP-1 upregulated significantly the six GDF members examined (GDF-1, -3, -5, -6, -8, and -9) by three- to four-fold. Our findings demonstrate that OP-1 differentially regulates the mRNA expression of several related members of the BMP family and upregulates the mRNA expression of several members of the GDF family. The observations suggest that OP-1 action on cartilage differentiation involves a complex regulation of gene expression of several members of the BMP and the GDF family.