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Effects of TGF-ß1 on Proliferation and IGFBP-3 Production in a Primary Culture of Human Fetal Epiphyseal Chondrocytes (HFEC)

Pediatric Endocrinology and Nutrition Research Unit - Department of Pediatrics, Children’s Hospital Vall d’Hebron, 08035. Barcelona, Spain

Abstract

Proliferation and differentiation of chondrocytes from growth cartilage are modulated by hormones and growth factors, among which TGF-ßs have been recognized as some of the more potent regulators although their specific cell efforts on cartilage physiology are not fully understood. Primary human fetal epiphyseal chondrocytes (HEFC) constitutively produce TGF-ß1 at different times of culture progression. Treatment of 48-h serum-deprived semiconfluent HFEC with 0.1-50 ng/ml of TGF-ß1 for 48-h decreased (³H)thymidine incorporation by 25–50% and cell number by 25%. In addition, IGFBP-3, the main insulin-like bonding protein produced by HFEC, showed a slight increase by TGF-ß1 in culture media. The changes in IGFBP-3 protein levels correlated well with its nRNA, indicating that TGF-ß1 is able to up-regulate IGFBP-3 systhesis in chondrocytes. Nevertheless, the IGFBP-3 accumulation in culture does not produce a clear growth inhibitory effect on chondrocytes. Thus, we conclude that even though TGF-· is able to up-regulate IGFBP-3, the growth inhibitory action produced by TGF-ß1 in not mediated by IGFBP-3 increase and appears to be mainly a direct TGF-ß1 effect on HFEC.

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