Elford P R, Lamberts S W
Sandoz Research Institute Berne Ltd., Switzerland.
Endocrinology. 1990 Oct;127(4):1635-9. doi: 10.1210/endo-127-4-1635.
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.
近期,人们已经认识到结缔组织中局部产生的胰岛素样生长因子-I(IGF-I)的重要性。据推测,合成代谢激素对骨骼的作用可能是通过局部释放IGF-I来介导的。然而,IGF-I是否也能被其他局部作用的细胞因子调节,这一问题尚未得到解决。转化生长因子-β(TGF-β)是一种被认为参与组织生长和修复调节的多肽。尽管TGF-β广泛存在,但在骨骼和软骨中含量特别高。在本研究中,研究了TGF-β1对成骨细胞和软骨细胞产生免疫反应性IGF-I的影响,并与甲状旁腺激素(PTH)对成骨细胞的影响或碱性成纤维细胞生长因子(bFGF)对软骨细胞的影响进行了比较。TGF-β1和PTH均刺激成骨细胞释放IGF-I,当二者同时存在时,这种刺激作用进一步增强。相反,尽管bFGF刺激软骨细胞释放IGF-I,但TGF-β1具有抑制作用,并且当二者同时存在时,TGF-β1还会减弱bFGF的作用。这些发现表明,骨骼和软骨中局部IGF-I产生的调节可能不同,并说明了局部细胞因子相互作用的复杂性。