Dexamethasone induces proliferation and terminal differentiation of osteogenic cells in tissue culture

Dexamethasone is an important regulator of cellular proliferation and differentiation, but paradoxical effects have been noted in a variety of culture systems. The purpose of this study was to determine whether dexamethasone induces proliferation and differentiation of osteogenic precursor cells. Periosteal explants from embryonic chicks were grown in culture for 3 or 4 days, treated continuously with dexamethasone or ethanol vehicle, and then either pulse-labeled with 3H-thymidine at 3 days or labeled for 24 hr between day 3 and day 4. Histochemical and autoradiographic procedures were used to assess the proliferation and differentiation of osteogenic cells. At 3 days, the area of bone, the percentage of alkaline phosphatase-positive cells, the percentage of 3H-thymidine-labeled cells, and the percentage of cells labeled with both markers were significantly higher in dexamethasone-treated cultures. Between day 3 and day 4 no significant changes in these parameters were observed in the dexamethasone-treated cultures. In comparison, control cultures exhibited significant increases in the percentage of 3H-thymidine-labeled cells after 24 hr of continuous labeling. The data show that dexamethasone induces a burst of proliferation in a cohort of cells that undergo differentiation. Once these cells have divided, further proliferation within the culture is limited. Finally, it is apparent that the timing of experiments may be critical in determining whether dexamethasone will inhibit or stimulate proliferation.