唑来膦酸对大鼠颌骨间充质干细胞成骨分化的影响  

Cellular and Molecular Mechanisms of Action of Zoledronic Acid on Mandible Mesenchymal Stem Cells in Rats

作　　者：龚雪[1] 苏俭生[1] 

机构地区：[1]同济大学口腔医学院口腔生物医学及转化医学实验室,上海200072

出　　处：《口腔颌面外科杂志》2015年第1期28-33,共6页Journal of Oral and Maxillofacial Surgery

基　　金：国家自然科学基金(81371949);上海市科学技术委员会项目(13411951201);教育部博士点基金(20110072110041)

摘　　要：目的:研究唑来膦酸对大鼠颌骨来源的间充质干细胞增殖、成骨分化及成骨因子RANKL/OPG m RNA表达的影响。方法:体外培养新生SD大鼠颌骨来源的间充质干细胞,观察不同浓度(0、0.5、1.0、2.0、4.0、8.0μg/m L)唑来膦酸对细胞增殖的影响。观察较高浓度唑来膦酸对细胞碱性磷酸酶活性、矿化结节形成以及成骨因子RANKL/OPG m RNA表达的影响。结果 :唑来膦酸≥1.0μg/m L能明显抑制细胞增殖,低浓度(0.5μg/m L)则不影响细胞增殖,高浓度唑来膦酸(2.0μg/m L)可抑制碱性磷酸酶活性、矿化结节的形成。高浓度唑来膦酸(2.0μg/m L)能使颌骨间充质干细胞RANKL m RNA表达减少,OPG m RNA表达增加,且明显下调成骨因子RANKL/OPG比率。结论:唑来膦酸在高浓度时明显抑制颌骨来源间充质干细胞的增殖和分化,并通过调节其表面RANKL/OPG m RNA表达,抑制破骨细胞的功能,骨生成与骨吸收同时减少,骨改建过程受抑制。Objective： To investigate the effect of zoledronic acid on the proliferation, osteogenic differentiation and the osteogenic factors RANKL/OPG mRNA expression of mandible mesenchymal stem cells（MSCs） in rats. Methods： The mes- enchymal stem cells isolated from the mandible of SD rats, were cultured with different concentrations of zoledronic acid ranging from 0~8 μg/mL. At 3 days after zoledronic acid intervention, CKK-8 assay was used to measure the absorbance to detect the effect of zoledronic acid on the proliferation of mandible mesenchymal stem cells. Cell alkaline phosphatase ac- tivity, mineralized nodules formation, RANKL/OPG expression of MSCs in rats to zoledronic acid were analyzed. Results： Zoledronic acid at the concentration of ≥ 1.0 μg/mL could inhibit the proliferation of MSCs, but it had no effect at the concentration of 0.5 p.g/mL. Zoledronic acid at the concentration of 2.0μg/mL could inhibit alkaline phosphatase activity, mineralized nodules formation of MMSCs. Zoledronic acid at the concentration of 2.0 μg/mL could down-regulate RANKL mRNA expression, but up-regulate OPG mRNA expression and down-regulate RANKL/OPG ratio. Conclusion： Zoledronic acid at high concentration can inhibit the proliferation and differentiation of MSCs. Whereas, it can inhibit the function of osteoclasts in bone remodeling by regulating the expression of MSCs cell-surface RANKL and OPG mRNA.

关 键 词：唑来膦酸 颌骨 间充质干细胞 增殖 分化 RANKL/OPG 大鼠 

分 类 号：R965[医药卫生—药理学]