Cortisol Modulation of Osteoblast Metabolic Activity in Cultured Neonatal Rat Bone

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Abstract
The effects of cortisol on basal levels of indices of osteoblast metabolic activity and on PTH [parathyroid hormone] regulation of osteoblast activity in vitro were examined in intact bone preparations from neonatal rat calvaria. Uniform punch sections from the frontal portion of calvaria of 3-day-old rats were cultured for 24 h at 37.degree. C in modified BGJb medium. When bone sections were incubated in medium supplemented with cortisol (100 nM) for 24 h, indices of osteoblast metabolic activity, expressed both per total bone section and per .mu.g bone DNA, were significantly increased relative to control values. Expressed per .mu.g DNA, the following percentage increases were observed in cortisol-treated cultures: alkaline phosphatase activity, +22% (P < 0.02); [3H]collagen synthesis, +41% (P < 0.001) and [14C]citrate decarboxylation, +108% (P < 0.001). Total DNA per bone section after 24 h was increased by 18% (P < 0.01) and [3H]thymidine incorporation at 24 h was increased by 26% (P < 0.01) relative to control values. Stimulation by cortisol occurred in a dose-related manner over concentrations from 1 nM to 1 .mu.M. The stimulatory effects of cortisol were first seen after 6 h of exposure and increased steadily through 24 h of exposure. Incubation in the presence of PTH-(1-34) (100 ng/ml) resulted in significant decrease in alkaline phosphatase activity, collagen synthesis and citrate decarboxylation after 24 h of exposure (P < 0.001). The relative order of sensitivity to PTH suppression was identical to the relative sensitivity to cortisol stimulation. In the presence of cortisol (100 nM), the suppressive effect of PTH on all 3 indices was increased significantly by a factor of 2- to 4-fold. In intact cultured bone, physiological concentrations of cortisol produce both an initial enhancement of indices of osteoblast metabolism and increased osteoblast sensitivity to regulation by PTH.