Tyler J A
Strangeways Research Laboratory, Cambridge, U.K.
Biochem J. 1989 Jun 1;260(2):543-8. doi: 10.1042/bj2600543.
A model system of explanted cartilage has been used in vitro to determine whether insulin-like growth factor 1 (IGF 1), which promotes matrix formation is effective in the presence of cytokines such as interleukin 1 (IL1) and tumour necrosis factor (TNF), which induce net matrix depletion. IGF 1 induced a dose-dependent 2.5-fold stimulation of proteoglycan synthesis, with a half-maximal dose of 25 ng/ml. A similar relative increase occurred in response to IGF 1 (10-100 ng/ml) in cartilage cultured also with IL1 or TNF (5-500 pM). There was no detectable qualitative change in the average molecular size or charge of the aggregating proteoglycan synthesized by explants exposed to IGF 1 alone or with IL1 or TNF. The increased production of prostaglandin E2, which is initiated when IL1 or TNF bind to the chondrocytes, was the same in the presence or absence of IGF 1. The time taken for 50% of pre-labelled proteoglycan to be released from the explants (t1/2) increased in the presence of IGF 1 (100 ng/ml) from 21 to 32 days in control cultures and from 8 to 26 days in cartilage cultured with IL1 (50 pM). It is concluded that IGF 1 enhances the synthesis of aggregating proteoglycan in cartilage exposed to cytokines and can directly decrease both the basal and the cytokine-stimulated degradation of proteoglycan in cartilage.
一种体外培养的软骨外植体模型系统被用于确定促进基质形成的胰岛素样生长因子1（IGF - 1）在诸如白细胞介素1（IL - 1）和肿瘤坏死因子（TNF）等细胞因子存在的情况下是否有效，这些细胞因子会导致净基质消耗。IGF - 1诱导蛋白聚糖合成呈剂量依赖性增加2.5倍，半数最大效应剂量为25 ng/ml。在用IL - 1或TNF（5 - 500 pM）培养的软骨中，对IGF - 1（10 - 100 ng/ml）也有类似的相对增加。单独暴露于IGF - 1或与IL - 1或TNF共同暴露的外植体合成的聚集蛋白聚糖的平均分子大小或电荷没有可检测到的定性变化。当IL - 1或TNF与软骨细胞结合时引发的前列腺素E2产量增加，在有或没有IGF - 1的情况下是相同的。在对照培养物中，存在IGF - 1（100 ng/ml）时，50%预先标记的蛋白聚糖从外植体中释放所需的时间（t1/2）从21天增加到32天，在用IL - 1（50 pM）培养的软骨中从8天增加到26天。结论是，IGF - 1增强了暴露于细胞因子的软骨中聚集蛋白聚糖的合成，并能直接降低软骨中蛋白聚糖的基础降解和细胞因子刺激的降解。
