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 osteoporo sis, 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 matr ix 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 bet a(1) integrin mRNA in the osteoblast layer but not in the periosteum. Northern blot analysis demonstrated a 62 per cent decrease in the leve ls of beta(1) integrin mRNA in the osteoblast layer of bone that had b een stripped of its periosteum. Immunofluorescence microscopy confirme d these results, as they demonstrated a decrease in the levels of beta (1) integrin protein predominantly in the osteoblast layer. This effec t was dependent on the concentration of corticosterone. During ninety- six hours of culture, the calcium content and the dry weight of contro l 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 glucoco rticoid had no significant effect on the DNA content or dry weight. Th us, the fetal-rat organ-culture system demonstrated a glucocorticoid-d ependent decrease in the formation of bone and in the synthesis of bet a(1) integrin in osteoblasts. CLINICAL RELEVANCE: The clinical manifes tation of osteoporosis suggests that many changes in the formation and remodeling of bone lead to a decrease in bone mass, We have studied t he effect of glucocorticoids on the expression of cell-attachment rece ptors (beta(1) integrins) in rat parietal bone, which forms osteoid an d mineralized bone in culture. In this mineralizing organ-culture syst em of glucocorticoid-induced osteoporosis, the loss of cell-attachment receptors appears to play a role in the decrease in mineralization. A n understanding of integrins and their role in the function of osteobl asts and the formation of bone may be useful in the treatment of stero id-induced osteoporosis and other metabolic bone diseases that may inv olve integrins, and this knowledge may help investigators to devise ne w therapeutic strategies to prevent the loss of bone.