Influence of Adrenalectomy and Dexamethasone on Matrix-Induced Endochondral Bone Differentiation

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Abstract
Effects of adrenalectomy and corticosteroid treatment on the temporal aspects of matrix-induced endochondral bone differentiation were examined using various biochemical parameters at discrete stages of development. In our previous study, we demonstrated a peak of ornithine decarboxylase (ODC) on day 3 concomitant with extensive proliferation of mesenchymal cells. Administration of corticosteroids, particularly dexamethasone, on days 0 and 1 or their implantation with bone matrix inhibited the increase in ODC activity, in contrast to other steroid hormones tested. Conversely, adrenalectomy increased the ODC activity over normal levels. Dexamethasone diminished the incorporation of 35SO4 into proteoglycans of the plaques during chondrogenesis on day 7, whereas adrenalectomy had no marked influence on this process. Dexamethasone treatment from days 7–10 impaired osteogenesis and mineralization, whereas treatment on days 10 and 11 did not affect osteogenesis and mineralization, as indicated by the levels of alkaline phosphatase and incorporation of 45Ca in plaques of days 11 and 12, respectively. However, in the latter group, the level of alkaline phosphatase was elevated in response to dexamethasone treatment. These results indicate that the action of corticosteroids on differentiation of endochondral bone may be mediated primarily through their influence on proliferation of mesenchymal cells before chondrogenesis and osteogenesis.