TRANSFORMING GROWTH-FACTOR-BETA AND BONE MORPHOGENETIC PROTEIN-2 ACT BY DISTINCT MECHANISMS TO PROMOTE CHICK LIMB CARTILAGE DIFFERENTIATIONIN-VITRO

A number of studies suggest that several members of the transforming g rowth factor-beta (TGF-beta) family of peptide growth factors may be i nvolved in the regulation of cartilage differentiation. It has been pr eviously reported that TGF-beta 1 and TGF-beta 2 promote the chondroge nic differentiation of chick limb mesenchymal cells in high density mi cromass cultures (Kulyk et al. [1989a] Dev. Biol. 135:424-430). In thi s study we report that chick limb mesenchymal cells express mRNA for c hicken TGF-beta 1, TGF-beta 2, and TGF-beta 3 during cartilage differe ntiation in vitro. In addition, the time course of their expression du ring cartilage differentiation is consistent with their playing a role in the initiation of this differentiation process. We also report tha t two members of the TGF-beta family, TGF-beta 3 and bone morphogeneti c protein-2 (BMP-S), are capable of promoting the accumulation of cart ilage extracellular matrix molecules by differentiating chick limb mes enchymal cells in micromass culture. Significant differences, however, were noted between the specific effects on matrix production elicited by these two growth factors which suggest that they may be acting by distinct mechanisms to regulate cartilage matrix production. TGF-beta appears to be most effective on cells which have not yet undergone cel l condensation, a critical event in early cartilage differentiation, w hereas BMP-2 is most effective after cells have condensed or different iated. These observations suggest that TGF-beta 3 and BMP-S may be act ing in a sequential manner to regulate chick limb mesenchymal cells th rough the different stages of cartilage differentiation. (C) 1994 Wile y-Liss, Inc.