Opposing effects by glucocorticoid and bone morphogenetic protein-2 in fetal rat bone cell cultures

✍ Scribed by Michael Centrella; Vicki Rosen; John M. Wozney; Sandra R. Casinghino; Thomas L. McCarthy

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 267 KB
• Volume: 67
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19971215)67:4<528::aid-jcb10>3.0.co;2-5

✦ Synopsis

Glucocorticoid in excess produces bone loss in vivo. Consistent with this, it reduces the stimulatory effect of transforming growth factor ␤ (TGF-␤) on collagen synthesis in osteoblast-enriched cultures in vitro, where it also suppresses TGF-␤ binding to its type I receptors. Analogous studies with bone morphogenetic protein-2 (BMP-2) show directly opposite results. These findings prompted us to assess the effect of glucocorticoid on BMP-2 activity in cultured bone cells, and whether either agent had a dominant influence on TGF-␤ binding or function. BMP-2 activity was retained in part in osteoblast-enriched cultures pre-treated or co-treated with cortisol, and was fully evident when glucocorticoid exposure followed BMP-2 treatment. In addition, BMP-2 suppressed the effects of cortisol on TGF-␤ activity, on TGF-␤ binding, and on gene promoter activity directed by a glucocorticoid sensitive transfection construct. While BMP-2 also alters the function of less-differentiated bone cells, it only minimally prevented cortisol activity in these cultures. Our studies indicate that BMP-2 can oppose certain effects by cortisol on differentiated osteoblasts, and may reveal useful ways to diminish glucocorticoid-dependent bone wasting.