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Transforming growth factor beta modulates proliferation of osteoblastic cells: relation to its effect on receptor levels for epidermal growth factor.

The effect of transforming growth factor beta (TGF-beta) on cellular proliferation of osteoblastic MC3T3-E1 cells was studied with particular emphasis on its effect on modulation of epidermal growth factor (EGF) receptors. In other cells, TGF-beta has been reported to augment EGF receptors. Exposure of MC3T3-E1 cells to TGF-beta initially increased cell surface EGF receptor levels and decreased the rate of DNA synthesis. The initial elevation of EGF receptor levels was due to increased receptor number per cell, not to changes in binding affinity. On the contrary, prolonged exposure (longer than 40 h) resulted in a decrease in EGF receptor and an increase in the rate of DNA synthesis. Thus, the effects of TGF-beta on these cells appears to be biphasic, reflecting complex mechanisms of action; the early effects of TGF-beta may be consistent with cellular differentiation to the osteoblastic phenotype with decreased cellular proliferation, whereas chronic exposure of these cells to TGF-beta stimulated cellular proliferation and inhibited osteoblastic phenotype expression. It is not likely that stimulation of cellular proliferation was through elevation of EGF receptor levels, because TGF-beta did not enhance the stimulatory effect of EGF on cellular proliferation. Thus, we conclude that TGF-beta possesses a stimulatory effect on the cellular proliferation of osteoblastic MC3T3-E1 cells independent of its modulative effect on EGF receptor level.