Temporal changes in the response of chick limb bud mesodermal cells to transforming growth factor beta-type 1.

Transforming growth factor beta (TGF beta) has been found in adult and developing bone in vivo and has varied effects on chondrocytes and osteoblasts in culture. We investigated the effects of TGF beta-type 1 on embryonic chick endochondral bone precursors in culture. Stage 24 chick limb bud mesoderm cells were cultured at high density. Under these conditions a dense mat containing nodules of cartilage surrounded by alkaline phosphatase-positive cells formed. Exposure of mesodermal cells to TGF beta-type 1 over the course of 4-7 days or during Days 3 and 4 caused a reduction in alkaline phosphatase activity and [35S]sulfate incorporation into proteoglycans. When the TGF beta-type 1 was applied during Days 1-2, it caused an increase in both parameters: these increases were observed in the absence of a corresponding change in [3H]thymidine incorporation. The specificity of the effects of TGF beta-type 1 was confirmed by neutralizing antibodies. These studies show that TGF beta-type 1 modulates the phenotype of embryonic endochondral bone precursors. The influence may depend on the window of exposure to the growth factor and, therefore, on the state of differentiation of the cells.