| 引用本文: | 刘宇佳,楼斯悦,章燕棋,曹戟,楼剑书,应美丹,何俏军.低氧激活自噬促进人间充质干细胞成骨分化的研究[J].中国现代应用药学,2016,33(3):284-289. |
| LIU Yujia,LOU Siyue,ZHANG Yanqi,CAO Ji,LOU Jianshu,YING Meidan,HE Qiaojun.Study of Hypoxia Induced Autophagy on Human Mesenchymal Stem Cells Differentiation[J].Chin J Mod Appl Pharm(中国现代应用药学),2016,33(3):284-289. |
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| 摘要: |
| 目的 探讨低氧对人间充质干细胞(human mesenchymal stem cells，hMSCs)成骨分化的效应及分子机制。方法 在正常氧压(20% O2)和低氧(5% O2)条件下培养hMSCs；采用成骨分化诱导液(BDM)诱导hMSCs成骨分化；利用茜素红染色法考察细胞钙沉积情况；通过Western blotting检测细胞自噬相关蛋白的表达水平以及MAPK、PI3K-AKT-mTOR信号通路的激活情况。结果 低氧条件下，hMSCs钙沉积较常氧条件增强；BDM诱导hMSCs成骨分化过程伴随着LC3表达增加，抑制细胞自噬可以明显减弱低氧促进的细胞钙沉积；低氧促进的细胞发生钙沉积伴随着MAPK以及PI3K-AKT-mTOR信号通路的失活；抑制MAPK以及PI3K-AKT-mTOR信号通路有利于细胞自噬发生，进而促进hMSCs钙沉积。结论 低氧下可以通过激活细胞自噬来促进hMSCs成骨分化，抑制MAPK以及PI3K-AKT-mTOR信号通路可以进一步促进细胞自噬的发生，从而协同促进hMSCs成骨分化。 |
| 关键词: 人间充质干细胞 低氧 自噬 钙沉积 成骨分化 |
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| 基金项目:浙江省自然科学基金项目(LY13H310002)；浙江省教育厅项目(Y201430401) |
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| Study of Hypoxia Induced Autophagy on Human Mesenchymal Stem Cells Differentiation |
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LIU Yujia1, LOU Siyue1, ZHANG Yanqi1,2, CAO Ji1, LOU Jianshu1, YING Meidan1, HE Qiaojun1
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1.Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Zhejiang Province Key Laboratory of Anti-cancer Drug Research, Hangzhou 310058, China;2.Department of Pharmacy, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou 310007, China
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| Abstract: |
| OBJECTIVE To explore the effects and molecular mechanisms of hypoxia on hMSCs differentiation. METHODS hMSCs were cultured under normoxic or hypoxic conditions; hMSCs differentiation were obtained by treated with BDM(bone differentiation medium); Calcium deposit was assessed by Alizard Red S dye; The protein levels were analyzed by western blotting. RESULTS Hypoxia can significantly promoted calcium deposit in hMSCs; The expression of LC3 was increased in hMSCs, hypoxia induced calcium deposit was inhibited by autophagy inhibitor 3MA; Hypoxia induced hMSCs calcium deposit was accompanied by inactivation of MAPK and PI3K-AKT-mTOR pathway, inhibition of these pathway could mediate hMSCs calcium deposit by promoted autophagy. CONCLUSION Hypoxia can significantly triger hMSCs differentiation by induced autophagy, inhibition of MAPK and PI3K-AKT-mTOR pathway could contribute to autophagy which could mediate hMSCs differentiation. |
| Key words: human mesenchymal stem cells hypoxia autophagy calcium deposit osteoblastic differentiation |
