TERMINAL DIFFERENTIATION OF CHONDROCYTES IN CULTURE IS A SPONTANEOUS PROCESS AND IS ARRESTED BY TRANSFORMING GROWTH-FACTOR-BETA-2 AND BASICFIBROBLAST GROWTH-FACTOR IN SYNERGY

At Day 17 of in ovo development, chondrocyte hypertrophy including syn thesis of collagen X takes place in a limited region within the crania l part of chick embryo sternum. Here we analyze in suspension culture the differences in response to single growth factors of chondrocytes d erived from the cranial part versus cells derived from the caudal part . Cells from either part were cultured separately without serum in the presence of insulin-like growth factor-1, transforming growth factor beta 2, basic fibroblast growth factor, or thyroid hormones. In cultur e, chondrocytes derived from the cranial part of sterna from 14- to 18 -day-old chicken embryos become hypertrophic and initiated the synthes is of collagen X and alkaline phosphatase. These processes were enhanc ed by anabolic diffusible signals, such as those contained in fetal bo vine serum, insulinlike growth factor-1, or thyroxine. Cells derived f rom the caudal part lack this capacity and, instead, prevented hypertr ophy of cranial cells in cocultures, presumably by secreting diffusibl e signals. As candidate molecules, we have identified transforming gro wth factor beta 2 and basic fibroblast growth factor, which both were released by chondrocytes. Synergistic action of transforming growth fa ctor beta 2 and basic fibroblast growth factor was required to suppres s insulin-like growth factor-1-stimulated maturation of cranial chondr ocytes in culture. (C) 1995 Academic Press, Inc.