Effects of 1α,25-dihydroxyvitamin D3 and glucocorticoids on the growth of rat and mouse osteoblast-like bone cells

Summary The effects of 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) and its interaction with glucocorticoids to regulate bone cell growth were studied in osteoblast-like (OB) cell cultures. Owing to our earlier findings that species difference and cell density at the time of treatment modified hormonal responses, comparisons were made between rat and mouse cells and sparse and dense cultures. 1,25(OH)₂D₃ inhibited cell proliferation in both species regardless of cell density. The magnitude of inhibition was larger in mouse cells, but the sensitivity to 1,25(OH)₂D₃ was the same for both species. Other metabolites, 25(OH)D₃ and 24R,25(OH)₂D₃, were >100-fold less potent than 1,25(OH)₂D₃ even in serum-free medium, which is similar to their ratio of affinity for the 1,25(OH)₂D₃ receptor. Dexamethasone, as previously shown, inhibited sparse and dense mouse cell cultures and sparse rat cell cultures while stimulating dense rat cell cultures to grow. The inhibitory actions of 1,25(OH)₂D₃ were not additive to the inhibitory dexamethasone effects. However, 1,25(OH)₂D₃ addition resulted in attenuation of the stimulatory effect of dexamethasone. These responses to 1,25(OH)₂D₃ and dexamethasone were dependent on cell density and not selective attachment of certain cell types at either plating density. In conclusion, the findings demonstrated that 1,25(OH)₂D₃ exerts an inhibiting action on both mouse and rat bone cell proliferation. This effect must be reconciled with thein vivo beneficial actions of 1,25(OH)₂D₃ on bone metabolism. Also, the likelihood of decreased cell number must be considered when biochemical activities are assessed after vitamin D treatmentin vitro.