Effects of TGF-beta 1 on proliferation and IGFBP-3 production in a primaryculture of human fetal epiphyseal chondrocytes (HFEC)

Proliferation and differentiation of chondrocytes from growth cartilage are modulated by hormones and growth factors, among which TGF-beta s have been recognized as some of the more potent regulators although their specific c ell effects on cartilage physiology are not fully understood. Primary human fetal epiphyseal chondrocytes (HEFC) constitutively produce TGF-beta 1 at different times of culture progression. Treatment of 48-h. serum-deprived s emiconfluent HFEC with 0.1-50 ng/ml of TGF-beta 1 for 48-h. decreased (H-3) Thymidine incorporation by 25-50 % and cell number by 25 %. In addtion, IGF BP-3, the main insulin-like bonding protein produced by HFEC, showed a slig ht increase by TGF-beta 1 in culture media. The changes in IGFBP-3 protein levels correlated well with its mRNA, indicating that TGF-beta 1 is able to up-regulate IGFBP-3 synthesis in chondrocytes. Nevertheless, the IGFBP-3 a ccumulation in culture media does not produce a clear growth inhibitory eff ect on chondrocytes. Thus, we conclude that even though TGF-beta 1 is able to up-regulate IGFBP-3, the growth inhibitory action produced by TGF-beta 1 is not mediated by IGFBP-3 increase and appears to be mainly a direct TGF- beta 1 effect on HFEC.