Autocrine or paracrine transforming growth factor-β modulates the phenotype of chick embryo sternal chondrocytes in serum-free agarose culture

Sternal chondrocytes of 17-day-old chick embryos in serum-free agarose culture secrete transforming growth factor-β. Media conditioned by such cells prevent serum-induced chondrocyte hypertrophy and cause a phenotypic modulation in serum-free culture which is similar to that observed for chondrocytes in monolayer culture. The modulated cells lose the round shape of differentiated chondrocytes and increasingly with time resemble tendon fibroblasts embedded into agarose. In addition, they produce less matrix macromolecules which include collagen I rather than cartilage collagens II, IX, X, and XI. All of these effects are abolished upon addition to the conditioned media of a monoclonal antibody against recombinant human transforming growth factor-β2. The same factor caused effects closely similar to those elicited by conditioned media. Therefore, the phenotypic modulation in adhesion-dependent cultures of chondrocytes in vitro does not directly result from cell-matrix interactions but can be produced also in suspension culture under the direction of appropriate diffusible stimuli that include transforming growth factor-β. In addition, the results support the concept of transforming growth factor-β as a multifunctional cytokine acting differently on cells of the same developmental origin depending on their stage of differentiation.