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 d ifferentiation. Little is known, however, regarding the regulation of BMP g ene expression. Here we examined the effect of parathyroid hormone-related peptide (PTHrP) (1-141), a full-length form of PTHrP molecules, on the expr ession of BMP-4 mRNA in clonal mouse chondrogenic EC cells, ATDC5. In diffe rentiated ATDC5 cells, the expression of BMP-4 mRNA was inhibited by PTHrP (1-141), which stimulated cAMP accumulation and protein kinase A (PKA) acti vity in these cells. Dibutyryl cAMP, a permeable analog of cAMP, mimicked a nd H-89, a selective PKA inhibitor, blocked this effect of PTHrP (1-141). M oreover, actinomycin D attenuated the inhibition of BMP-4 mRNA expression b y PTHrP (1-141). These results indicate that PTHrP (1-141) transcriptionall y inhibits the expression of BMP-4 mRNA through a cAMP/PKA pathway in ATDC5 cells. (C) 2000 Elsevier Science B.V. All rights reserved.