高糖环境LIF介导STAT3/SOCS3信号通路参与成骨细胞分化机制研究

目的研究高糖环境下白血病抑制因子(leukemia inhibitory factor,LIF)介导STAT3/SOCS3信号通路对成骨细胞分化的影响及其作用机制。方法利用ELISA检测2型糖尿病患者血清白细胞介素6(interleukin-6,IL-6)家族中LIF及炎性因子的水平;通过RT-PCR、Western blot检测体外高糖环境下成骨分化标志物ALP、RUNX2、OCN、OPN以及细胞因子信号抑制因子3(suppressors of cytokine signaling,SOCS3)的m RNA和蛋白表达情况。结果 2型糖尿病患者血清炎性因子和LIF的水平明显升高。高糖或LIF显著降低了成骨分化标志物ALP、RUNX2、OCN和OPN的m RNA和蛋白水平,同时上调了SOCS 3和PSTAT3的表达。加入50 nmol/L或100 nmol/L STAT 3抑制剂JSI-124可改善成骨分化标志物的表达下调。结论 LIF通过介导STAT3/SOCS3信号通路参与高糖诱导下的成骨细胞分化。本研究为高糖导致的成骨障碍奠定了分子生物学理论基础并对靶点药物的研发提供了实验依据。

The mechanism of LIF-mediated osteoblast differentiation through STAT3/SOCS3 signaling pathway in high glucose environment

Objective To study the influence and mechanism of STAT3/SOCS3 signaling pathway mediated by leukemia inhibitory factor (LIF) on osteoblast differentiation in high glucose environment. Methods Detection of LIF and inflammatory factors in serum Interleukin-6 Family by ELISA in patients with diabetes mellitus. Detection of mRNA and protein expression of osteogenic differentiation markers ALP, RUNX2, OCN and OPN and suppressors of cytokine signaling 3 by RT-PCR and Western blot in vitro high glucose environment. Results The levels of serum inflammatory factors and LIF were significantly increased in diabetes mellitus patients. High glucose or LIF significantly decreased the mRNA and protein levels of ALP, RUNX2, OCN and OPN, at the same time up-regulated the expression of SOCS3 and P-STAT3. 50 nmol/L or 100 nmol/L STAT 3 inhibitor JSI-124 could improve osteogenic differentiation and down-regulate the expression of osteoblast differentiation markers. Conclusion LIF plays an important role in the differentiation of osteoblasts induced by high glucose through mediating STAT3/SOCS3 signaling pathway. This study lays on the theoretical foundation of molecular biology for high glucose-induced osteogenesis and provides experimental basis for target drug development.