Mechanisms of glucocorticoid action in bone cells.

Glucocorticoids play an important role in the normal regulation of bone remodeling; however continued exposure of bone to glucocorticoid excess results in osteoporosis. In vivo, glucocorticoids stimulate bone resorption and decrease bone formation, and in vitro studies have shown that while glucocorticoids stimulate osteoblastic differentiation, they have important inhibitory actions on bone formation. Glucocorticoids have many effects on osteoblast gene expression, including down-regulation of type I collagen and osteocalcin, and up-regulation of interstitial collagenase. The synthesis and activity of osteoblast growth factors can be modulated by glucocorticoids as well. For example, insulin-like growth factor I (IGF-I) is an important stimulator of osteoblast function, and expression of IGF-I is decreased by glucocorticoids. The activity of IGF I can be modified by IGF binding proteins (IGFBPs), and their synthesis is also regulated by glucocorticoids. Thus, glucocorticoid action on osteoblasts can be direct, by activating or repressing osteoblast gene expression, or indirect by altering the expression or activity of osteoblast growth factors. Further investigation of the mechanisms by which glucocorticoids modulate gene expression in bone cells will contribute to our understanding of steroid hormone biology and will provide a basis for the design of effective treatments for glucocorticoid-induced osteoporosis.