CONTRASTING MODULATION BY TRANSFORMING GROWTH FACTOR-BETA-1 OF INSULIN-LIKE GROWTH FACTOR-I PRODUCTION IN OSTEOBLASTS AND CHONDROCYTES

The importance of locally produced insulin-like growth factor-I (IGF-I) in connective tissues has recently been recognized. It has been postulated that the action of anabolic hormones on bone may be mediated through local IGF-I release. However, whether IGF-I can also be modulated by other locally acting cytokines has not been addressed. Transforming growth factor- β (TGF β) is a polypeptide thought to be involved in the regulation of tissue growth and repair. Although the occurrence of TGF β is ubiquitous, particularly high amounts are found in bone and cartilage. In this study the effect of TGFβ-1 on immunoreactive IGF-I production by osteoblasts and chondrocytes was investigated and compared to that of PTH on osteoblasts or basic fibroblast growth factor (bFGF) on chondrocytes. Both TGF β -1 and PTH stimulated IGF-I release from osteoblasts, which was further enhanced when both were consecutively present. Contrastingly, although bFGF stimulated IGF-I release by chondrocytes, TGF β -1 was inhibitory and also blunted the effect of bFGF when both were present concurrently. These findings demonstrate that the regulation of local IGF-I production in bone and cartilage may differ and illustrate the complex nature of local cytokine interactions. © 1990 by The Endocrine Society.