THE EFFECT OF GLUCOCORTICOIDS ON OSTEOBLAST FUNCTION - THE EFFECT OF CORTICOSTERONE ON OSTEOBLAST EXPRESSION OF BETA(1) INTEGRINS

Prolonged treatment with glucocorticoids is known to produce osteoporosis, which is characterized by a decrease in bone mass. Therefore, we studied the effect of glucocorticoids on the formation of bone and on the expression of beta(1) integrins in a mineralizing organ culture of fetal rat parietal bone. Integrins are a family of integral membrane glycoproteins that mediate the adhesion of cells to extracellular matrix macromolecules and affect the growth and differentiation of cells. In situ hybridization with a P-32-labeled beta(1) integrin cDNA probe was performed on parietal bone, treated with or without 100-nanomolar corticosterone for ninety-six hours, to localize and assess the levels of beta(1) integrin mRNA quantitatively. Corticosterone decreased beta(1) integrin mRNA in the osteoblast layer but not in the periosteum. Northern blot analysis demonstrated a 62 per cent decrease in the levels of beta(1) integrin mRNA in the osteoblast layer of bone that had been stripped of its periosteum. Immunofluorescence microscopy confirmed these results, as they demonstrated a decrease in the levels of beta(1) integrin protein predominantly in the osteoblast layer. This effect was dependent on the concentration of corticosterone. During ninety-six hours of culture, the calcium content and the dry weight of control parietal bone increased 157 per cent and 57 per cent, respectively. However, treatment of these cultures with 100-nanomolar corticosterone inhibited calcification by 24 per cent. The administration of glucocorticoid had no significant effect on the DNA content or dry weight. Thus, the fetal-rat organ-culture system demonstrated a glucocorticoid-dependent decrease in the formation of bone and in the synthesis of beta(1) integrin in osteoblasts. CLINICAL RELEVANCE: The clinical manifestation of osteoporosis suggests that many changes in the formation and remodeling of bone lead to a decrease in bone mass, We have studied the effect of glucocorticoids on the expression of cell-attachment receptors (beta(1) integrins) in rat parietal bone, which forms osteoid and mineralized bone in culture. In this mineralizing organ-culture system of glucocorticoid-induced osteoporosis, the loss of cell-attachment receptors appears to play a role in the decrease in mineralization. An understanding of integrins and their role in the function of osteoblasts and the formation of bone may be useful in the treatment of steroid-induced osteoporosis and other metabolic bone diseases that may involve integrins, and this knowledge may help investigators to devise new therapeutic strategies to prevent the loss of bone.