Transforming growth factor-(3 (TGF-p) niodulates growth and differentiation in many cell types and is abundant in bone matrix. We recently showed that human cord blood monocytes cultured in the presence of 1,25(OH),D, acquire some features of osteoclast precursors. Since TGF-P has been shown to influence bone resorption in organ culture, we have studied the effect of TGF-P (1-1,000 pgiml) on cord blood monocyte cultures. These cells were cultured on plastic substrate during 3 weeks in the presence of 20% horse serum and 10 M 1,25(0H),D,.
TGF-P, from a concentralion of 10 pgiml in the culture medium, decreased in a dose dependent manner the formation of multinucleated cells. At a concentration of TGF-p of 1 ngiml, the multinucleated cells were reduced to 2.1% * 0.3%, compared to 19.3% i 1.5% in control cultures. TGF-P inhibited in a dosedependent manner the proliferation of cord blood monocyte5 as assessed by 'H-thymidine incorporation at 7 and 14 days of culture. The fusion index was also decreased by .3 weeks of treatment with TGF-(3. lndomethacin did not reverse the inhibitory effects of TGF-P. The expression of the osteoclastic phenotype was assessed using two different antibodies: 2 K 6 , a monoclonal antibody directed against the vitronectin receptor, which is highly expressed by osteoclasts but not by adult monocytes, and an antibody to HLA-DK, which is not present on osteoclast. TGF-P decreased the expression of HLA-DK and increased in a dose-dependent manner the proportion of 23Cb-labcled cells; these results suggest that TGF-P could modulate a differentiation effect to the osteoclastic phenotype. However, when cord blood monocytes were cultured on devitalized rat calvariae prelabeled with "'Ca, TGF-P did not induce any 4'Ca release from bone cultured with monocytes, suggesting that full osteoclastic differentiation was not achieved.
These results emphasize the complex role of TGF-P in the local regulation of bone cell differentiation and in bone remodeling.