晚期糖化终末产物对人成骨细胞增殖及分泌细胞因子的影响

Effects of advanced glycosylation end product on human osteoblastic cell proliferation and secreting cytokine

目的 探讨晚期糖化终末产物对人成骨细胞增殖及分泌细胞因子的影响 ,以期揭示晚期糖化终末产物在骨质疏松发病中的作用。方法 用体外制备的AGE 牛血清白蛋白 (AGE BSA)加入人成骨细胞培养体系 ,观察不同浓度AGE和不同作用时间 ,对人成骨细胞增殖及分泌白细胞介素 6 (IL 6 )和肿瘤坏死因子 α(TNF α)的影响。结果 加入AGE BSA 2 4h后 ,低浓度抑制成骨细胞增殖 ;培养 48、72h后 ,浓度依赖性的促增殖作用增强。加入AGE BSA 48h ,10 0 μg mlAGE BSA促进成骨细胞分泌IL 6。 2 0 0 μg ml～ 10 0 0 μg ml对IL 6及TNF α的分泌均无显著影响。 结论 晚期糖化终末产物对人成骨细胞表现出在较高浓度时 ,仍具有很强的促增殖活性 ,提示人对高浓度AGE的耐受性增强。AGE在较高浓度对人成骨细胞分泌IL 6和TNF α无显著影响。提示由随龄增加的AGE在老年人引起的成骨细胞介导的骨吸收没有明显增加 ,与老年性骨质疏松为低转换型结果相一致。

Objective\ Exploring the effects of advanced glycosylation end product (AGE) on human osteoblastic cell proliferation and secreting cytokines,for revealing the role of AGE in the pathogenesis of senile osteoporosis. Methods\ Cells from fetal calvaria were incubated for different periods of time after exposure to different doses of AGE\|BSA or BSA so as to assess time\|dependent and dose\|dependent pattern of AGE\|BSA effect on human osteoblastic cell proliferation and secreting cytokine. Results\ After 48 h incubation,100 μg/ml AGE\|BSA significantly promoted the secretion of IL\|6 from human osteoblastic cells.There was no significant difference in production of IL\|6 and TNF\|α between AGE\|BSA and BSA at doses ranging from 200 μg/ml to 1000 μg/ml AGE\|BSA.After 24 h incubation,100 μg/ml AGE\|BSA significantly inhibited human osteoblastic cell proliferation.After 48 h and 72 h incubation,100-1000 μg/ml AGE\|BSA significantly induced a dose\|dependent increase in human osteoblastic cell proliferation. Conclusion\ High concentration of AGE induces strongly stimulative effect on human osteoblastic cell proliferation,suggesting that human osteoblastic cells have an increased tolerance to high level AGE,which might be associated with the life span of different species.There is no significant differencent in effects on IL\|6 and TNF α production between AGE\|BSA and BSA after exposure of the cells to high level AGE,suggesting that osteoblast\|mediated bone resorption induced by increased AGE is not obviously increased.This fact corresponds with decreased bone turnover in old people,who have higher AGE in their body.\;