Bone morphogenetic protein-4 regulates its own expression in cultured osteoblasts

During development, bone morphogenetic proteins (BMPs) induce the different iation of mesenchymal progenitor cells to enter into the osteoblastic linea ge, and BMPs enhance osteoblastic function. BMPs and noggin, a specific bin ding protein that blocks BMP actions, are expressed by osteoblastic cells b ut there is limited information about regulation of BMP synthesis in skelet al cells. We tested for the expression and regulation of BMP-4 in cultures of osteoblast-enriched cells from 22-day fetal rat calvariae (Ob cells). BM P-4 caused a short-lived increase in BMP-4 mRNA followed by a marked inhibi tion of BMP-4 expression. The stimulatory effect was transcriptional, as de termined by nuclear run-on assays, whereas the inhibitory effect was transc riptional and posttranscriptional, because longer BMP-4 exposure decreased its rate of transcription and shortened the half-life of BMP-4 mRNA in tran scriptionally arrested Ob cells. BMP-2 and BMP-6 also inhibited BMP-4 mRNA levels. Transforming growth factor beta 1 increased, whereas fibroblast gro wth factor-2, platelet-derived growth factor BE, and insulinlike growth fac tor 1 decreased BMP-4 mRNA in Ob cells. BMP-2. also was expressed by Ob cel ls and it was downregulated by BMP-2, BMP-4, and BMP-6. Noggin increased BM P-4 transcripts, suggesting autocrine control of BMP-4 expression. In concl usion, BMP-4 inhibits its own expression in Ob cells, a mechanism to limit BMP availability to osteoblasts. (C) 2000 Wiley-Liss, Inc.