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Biochim Biophys Acta. 1999 Sep 21;1451(2-3):263-70.

Bone morphogenetic protein-6 and parathyroid hormone-related protein coordinately regulate the hypertrophic conversion in mouse clonal chondrogenic EC cells, ATDC5.

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Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan.


We evaluated the roles of bone morphogenetic protein (BMP)-6, BMP-4 and parathyroid hormone-related protein (PTHrP) in the hypertrophic conversion using mouse chondrogenic EC cells, ATDC5. In ATDC5 cells, the expression of BMP-6 and PTHrP receptor mRNAs increased in parallel with the progression of chondrogenic differentiation of these cells, exhibiting a time course similar to that of type II collagen, a phenotypic marker of proliferating chondrocytes, while BMP-4 mRNA was continuously expressed throughout the differentiation processes. The expression of type X collagen mRNA, a phenotypic marker of hypertrophic chondrocytes, was upregulated by BMP-6 and BMP-4, and downregulated by PTHrP(1-141). The expression of BMP-6 mRNA was upregulated while that of BMP-4 mRNA was downregulated by both BMP-6 and BMP-4. Moreover, the expression of BMP-6 mRNA was downregulated by PTHrP(1-141). Furthermore, even in the presence of PTHrP(1-141), BMP-6 increased the transcript level of type X collagen in a dose-dependent manner. These results indicate that transiently expressed BMP-6 promotes the hypertrophic conversion in association with the augmentation of BMP-6 gene expression by BMP signals and that both BMP-6 and PTHrP coordinately regulate the rate of the hypertrophic conversion of ATDC5 cells.

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