REDUCTION IN TRANSFORMING-GROWTH-FACTOR-BETA RECEPTOR-I EXPRESSION AND TRANSCRIPTION FACTOR CBFA1 ON BONE-CELLS BY GLUCOCORTICOID

Glucocorticoid in excess suppresses bone formation in. vivo and disrup ts bone matrix protein synthesis by osteoblasts in vitro, In contrast, transforming growth factor beta (TGF-beta) potently enhances bone mat rix apposition. The rat TGF-beta type I receptor gene promoter contain s 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 effect s of glucocorticoid on bone loss may be mediated in part by suppressio n of CBFa1, with a resultant decrease in the expression and activity o f the TGF-beta type I receptor on matrix-producing bone cells.