Reduction in transforming growth factor β receptor I expression and transcription factor CBFa1 on bone cells by glucocorticoid

Abstract

Glucocorticoid in excess suppresses bone formation in vivo and disrupts bone matrix protein synthesis by osteoblasts in vitro. In contrast, transforming growth factor β (TGF-β) potently enhances bone matrix apposition. The rat TGF-β type I receptor gene promoter contains cis-acting elements for transcription factor CBFa1, which increases in parallel with osteoblast differentiation. Here we present molecular data linking these events. We show that previously unexplained effects of glucocorticoid on bone loss may be mediated in part by suppression of CBFa1, with a resultant decrease in the expression and activity of the TGF-β type I receptor on matrix-producing bone cells.