高浓度他克莫司抑制人间充质干细胞的增殖和成骨细胞分化

Q4 Pharmacology, Toxicology and Pharmaceutics

中国药理学与毒理学杂志 Pub Date : 2011-06-01 DOI:10.3867/J.ISSN.1000-3002.2011.03.001

H. Wei, W. Pan, Ni Qiu, Li Huang, Hong-hao Zhou, Zhousheng Xiao

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引用次数: 0

摘要

目的探讨他克莫司对人骨髓间充质干细胞(hBMSCs)细胞增殖和成骨分化的影响。方法以他克莫司0.001 ~ 5 μmol·L-1培养hBMSCs。用BrdU掺入评价细胞增殖，用碱性磷酸酶(ALP)活性和钙沉积评价hBMSCs的成骨分化。采用商业CaN检测试剂盒检测钙调神经磷酸酶(calcalineurin, CaN)活性，Western blotting检测核心结合因子1 α亚基(Cbfα1)蛋白水平。结果他克莫司0.001 ~ 0.1 μmol·L-1可促进BrdU掺入，但对ALP活性和钙沉积无影响，而他克莫司0.5 ~ 5 μmol·L-1可通过降低BrdU掺入、ALP活性和钙沉积而显著降低hBMSCs培养物的增殖和成骨细胞成熟，并呈浓度依赖性。此外，他克莫司0.5 ~ 5 μmol·L-1可导致CaN活性呈浓度依赖性下降，这与他克莫司处理后细胞中Cbfα1蛋白表达下调一致。结论高浓度他克莫司可能通过CaN/Cbfα1通路抑制hBMSCs的增殖和成骨分化。

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High concentration of tacrolimus inhibits proliferation and osteoblastic differentiation of human mesenchymal stem cells

OBJECTIVE To investigate the effect of tacrolimus on cell proliferation and osteoblastic differentiation of primary human bone marrow-derived mesenchymal stem cells(hBMSCs).METHODS hBMSCs were cultured with tacrolimus 0.001-5 μmol·L-1.BrdU incorporation was used to assess the cell proliferation while cellular alkaline phosphatase(ALP) activity and calcium deposition were measured to evaluate the osteoblastic differentiation of hBMSCs cultures.The calcineurin(CaN) activity was also examined using commercial CaN assay kit,and core binding factor 1 alpha subunit(Cbfα1) protein level was determined by Western blotting.RESULTSTacrolimus 0.001-0.1 μmol·L-1 promoted BrdU incorporation but had no effect on ALP activity and calcium deposition,whereas tacrolimus 0.5-5 μmol·L-1 resulted in significant decrease in both cell proliferation and osteoblastic maturation,by reducing BrdU incorporation,ALP activity,and calcium deposition of hBMSCs cultures in a concentration-dependent manner.In addition,tacrolimus 0.5-5 μmol·L-1 led to concentration-dependent decrement in CaN activity,which was consistent with down-regulated Cbfα1 protein in the tacrolimus treated cells.CONCLUSION High concentration of tacrolimus might inhibit the cell proliferation and osteoblastic differentiation of hBMSCs cultures through a CaN/Cbfα1 pathway.

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来源期刊

中国药理学与毒理学杂志 Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

0.20

自引率

0.00%

发文量

6787

期刊介绍： Chinese Journal of Pharmacology and Toxicology was first published in November 1986. As a journal of high academic value jointly edited by the Chinese Pharmacological Society, Chinese Society of Toxicology and the Academy of Military Medical Sciences (AMMS), it is a dominating one in China’s biomedicine, devoted to publication of research findings, reviews of special topic and new technologies and methods in every branch of experimental toxicology and pharmacology.