Age-related changes in effects of insulin-like growth factor I on human osteoblast-like cells
Age-related changes in effects of insulin-like growth factor I on human osteoblast-like cells
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DOI：
10.1042/bj3240753
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发表时间：
1997-06-15
影响因子：
4.1
通讯作者：
Fedarko, NS
中科院分区：
文献类型：
--
作者：
dAvis, PY;Frazier, CR;Fedarko, NS
胰岛素样生长因子I （IGF-I）在细胞外基质代谢中的作用研究了来自不同年龄供体的增殖和融合人成骨样培养。在增殖培养中，发现重组人（rh） igf - 1以剂量和年龄依赖的方式增加[H-3]胸腺嘧啶的掺入。为了动态研究细胞增殖，用修正logistic函数建立了有和不含rhIGF-I的连续生长曲线。增加rhigf - 1的剂量减少了滞后时间和最大生长速率，而平台值仅在最高剂量（100 ng/ml）时下降。在增殖后的细胞株中，rhigf -1 （0.1-100 ng/ml）增加了I型胶原蛋白、高聚糖和decorin的水平，并在较小程度上增加了纤维连接蛋白和血栓反应蛋白的水平，而当蛋白质和蛋白聚糖代谢之后用[H-3]脯氨酸、[H-3]葡萄糖胺或[S-35]硫酸盐进行稳态放射性标记时，rhigf -1降低了透明质酸和一种花式蛋白聚糖的水平。这些对rhigf - 1的反应是年龄依赖性的，来自年轻患者的成骨细胞样细胞对rhigf - 1的反应更强。当通过脉冲追踪实验分析细胞外基质周转时，rhIGF-I没有影响。在培养第7天，经rhigf - 1处理的骨细胞的胶原蛋白、装饰素、透明质酸和花式蛋白多糖的稳态水平与未处理的成骨细胞生长14天的这些基质成分的水平相当。这些结果与rhIGF-I改变细胞增殖能力和基质合成，导致成骨细胞分化状态的改变是一致的。
The role of insulin-like growth factor I (IGF-I) in extracellular matrix metabolism was studied in both proliferating and confluent human osteoblast-like cultures derived from donors of different ages. In proliferating cultures, recombinant human (rh)IGF-I was found to increase the incorporation of [H-3]thymidine in a dose- and age-dependent manner. To study cell proliferation dynamically, continuous growth curves with and without rhIGF-I were modelled by a modified logistic function. Increasing doses of rhIGF-I decreased the lag time and maximal growth rates, whereas plateau values decreased only at the highest dose (100 ng/ml). In post-proliferative cell strains, rhIGF-I (0.1-100 ng/ml) increased levels of type I collagen, biglycan and decorin, and to a smaller extent fibronectin and thrombospondin, whereas it decreased the levels of hyaluronan and a versican-like proteoglycan when protein and proteoglycan metabolism were followed by steady-state radiolabelling with [H-3]proline, [H-3]glucosamine or [S-35]sulphate. These responses to rhIGF-I were found to be age-dependent, with osteoblast-like cells derived from younger patients being more responsive to rhIGF-I. When extracellular matrix turnover was analysed by pulse-chase experiments, rhIGF-I had no effect. The steady-state levels of collagen, decorin, hyaluronan and a versican-like proteoglycan for bone cells treated with rhIGF-I on day 7 in culture were equivalent to levels of these matrix components in untreated osteoblasts grown for 14 days. These results are consistent with rhIGF-I's altering cellular proliferative capacity and matrix synthesis, causing a change in the osteoblast differentiated state.