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-beta (TGF beta) is a polypeptide thought to be involved in the regulation of tissue growth and repair. Although the occurrence of TGF beta is ubiquitous, particularly high amounts are found in bone and cartilage. In this study the effect of TGF beta-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 beta-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 beta-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.
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