Parathyroid hormone-related peptide inhibits the expression of bone morphogenetic protein-4 mRNA through a cyclic AMP/protein kinase A pathway in mouse clonal chondrogenic EC cells, ATDC5.

The bone morphogenetic proteins (BMPs) play crucial roles in chondrogenic differentiation. Little is known, however, regarding the regulation of BMP gene expression. Here we examined the effect of parathyroid hormone-related peptide (PTHrP) (1-141), a full-length form of PTHrP molecules, on the expression of BMP-4 mRNA in clonal mouse chondrogenic EC cells, ATDC5. In differentiated ATDC5 cells, the expression of BMP-4 mRNA was inhibited by PTHrP (1-141), which stimulated cAMP accumulation and protein kinase A (PKA) activity in these cells. Dibutyryl cAMP, a permeable analog of cAMP, mimicked and H-89, a selective PKA inhibitor, blocked this effect of PTHrP (1-141). Moreover, actinomycin D attenuated the inhibition of BMP-4 mRNA expression by PTHrP (1-141). These results indicate that PTHrP (1-141) transcriptionally inhibits the expression of BMP-4 mRNA through a cAMP/PKA pathway in ATDC5 cells.