Opposing effects by glucocorticoid and bone morphogenetic protein-2 in fetal rat bone cell cultures.
Glucocorticoid in excess produces bone loss in vivo. Consistent with this, it reduces the stimulatory effect of transforming growth factor beta (TGF-beta) on collagen synthesis in osteoblast-enriched cultures in vitro, where it also suppresses TGF-beta 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-beta 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-beta activity, on TGF-beta 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.
Centrella
M
M
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8041, USA. centrellma@maspo3.mas.yale.edu
Rosen
V
V
Wozney
J M
JM
Casinghino
S R
SR
McCarthy
T L
TL
D030201:Activin Receptors, Type I; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D005333:Fetus; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007700:Kinetics; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology
C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D005938:Glucocorticoids; D017395:Plasminogen Activator Inhibitor 1; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D003094:Collagen; D004247:DNA; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat; D000469:Alkaline Phosphatase; D006854:Hydrocortisone