Effect of cortisol on periosteal and nonperiosteal collagen and DNA synthesis in cultured rat calvariae

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Abstract
The effects of cortisol on bone formation are complex and may be modulated by the presence of periosteal cells or by factors released by the periosteal tissue. To test these possibilities, cortisol was examined for its effects on the incorporation of3H-proline into collagenase-digestible protein (CDP) and noncollagen protein (NCP), on DNA synthesis and on alkaline phosphatase activity in intact and in the periosteum and nonperiosteal bone of dissected calvariae from 21-day-old fetal rats. After 24 h of treatment, cortisol increased the incorporation of3H-proline into CDP in intact bones and in the nonperiosteal bone of calvariae dissected after the culture. Cortisol inhibited the incorporation of3H-thymidine into calvarial DNA but it caused a small increase in nonperiosteal DNA content. Cortisol did not affect the incorporation of3H-proline into CDP in calvariae dissected prior to the culture if the periosteum and nonperiosteal central bone were incubated separately; the stimulatory effect was observed only if the two tissues were cultured in the same vial and were in contact. In contrast, cortisol stimulated alkaline phosphatase activity in the central nonperiosteal bone of calvariae dissected before or after the culture. After 72–96 h of treatment, cortisol inhibited the labeling of CDP, NCP, and DNA and the DNA content in intact bones and in both periosteal and nonperiosteal central bone of calvariae dissected after the culture. In contrast, when the periosteum was removed before the incubation, these inhibitory effects were observed in the periosteum and not in the nonperiosteal bone. Cortisol inhibited alkaline phosphatase activity in intact bones treated for 96 h, but removal of the periosteum resulted in a stimulatory effect in the nonperiosteal central bone. These studies indicate that 24 h treatment with cortisol stimulates collagen synthesis in nonperiosteal bone, an effect that requires the presence of periosteal tissue. Exposure to cortisol for 72–96 h inhibits collagen, noncollagen protein, and DNA synthesis, an effect that is secondary to an inhibition of periosteal cell replication. Cortisol does not cause a direct inhibition of osteoblastic function.