TGF-β1通过组蛋白修饰酶调控人骨髓间充质干细胞成骨分化的表观基因学研究OA北大核心CSTPCD
Epigenetic study of TGF-β1 regulation on osteogenic differentiation of human bone marrow mesenchymal stem cells through histone modifying enzymes
目的 研究骨髓间充质干细胞(bone marrow mesenchymal stem cells,BMSCs)成骨分化过程中转化生长因子β1(transforming growth factor β1,TGF-β1)/Smad信号通路与组蛋白甲基化酶和去甲基化酶的相关性.方法 BMSCs成骨诱导培养,用TGF-β1、SB431542 和TGF-β1+SB431542 干预.分为 4 组:BMSCs-Ctrl-3d组(A 组),BMSCs-Ctrl-ost3d 组(B 组),BMSCs-TGF-β1-ost3d 组(C 组),BMSCs-TGF-β1-SB1UM-ost3d组(D组).用qRT-PCR方法检测各组甲基化酶和去甲基化酶mRNA表达量.结果 (1)与A组比较,B组DM3B、KDM4A、KDM4B、KDM4C、KDM4D、KDM5A、KDM5B、KDM5C、KDM6A、KDM6B、EZH1 的mRNA表达明显增强(P＜0.05).(2)与 B 组比较,C 组 KDM3B、KDM4A、KDM4C、KDM4D、KDM5C、EZH1 的mRNA表达明显降低(P＜0.05);KDM5B、KDM6A、KDM6B的mRNA表达明显增强(P＜0.05);而KDM4B、KDM5A表达无明显改变(P＞0.05).(3)与C组比较,D组KDM3B、KDM6A、KDM6B的mRNA表达发生明显改变(P＜0.05);KDM4C、KDM4D、KDM5C和EZH1 的mRNA改变不显著(P＞0.05),KDM4A的mRNA发生非特异性改变(P＜0.05).结论 TGF-β1 通过TGF-β1/Smad信号通路和TGF-β1/非Smad信号调控部分相关组蛋白甲基化转移酶/去甲化酶的表达,从而促进了BMSCs成骨分化.
Objective To investigate the relationship between transforming growth factor β1(TGF-β1)/Smad signaling pathway and histone methylase/demethylase during osteogenic differentiation of bone marrow mesenchy-mal stem cells(BMSCs).Methods BMSCs were subjected to osteogenic induction,then TGF-β1,SB431542 and TGF-β1+SB431542 were incubated in the osteogenic induction medium.The BMSCs were divided into four groups:BMSCs-Ctrl-3d group(group A),BMSCs-Ctrl-ost3d group(group B),BMSCs-TGF-β1-ost3d group(group C),BM-SCs-TGF-β1-SB1UM-ost3d group(group D).qRT-PCR was used to test the mRMA expression levels of histone lysine methyltransferase/demethylase.Results Compared with group A,mRNA expressions of KDM3B,KDM4A,KDM4B,KDM4C,KDM4D,KDM5A,KDM5B,KDM5C,KDM6A,KDM6B and EZH1 in group B were significantly increased(P＜0.05).Compared with group B,the expressions of KDM3B,KDM4A,KDM4C,KDM4D,KDM5C and EZH1 in group C were significantly decreased(P＜0.05).The mRNA expressions of KDM5B,KDM6A and KDM6B in group C were significantly increased(P＜0.05).The changes of mRNA expressions of KDM4B and KDM5A were not significant(P＞0.05).Compared group C and group D,the mRNA expressions of KDM3B,KDM6A and KDM6B were significant-ly different(P＜0.05).The changes of KDM4C,KDM4D,KDM5C and EZH1 were not significant(P＞0.05),and the mRNA expression change of KDM4A was significant but non-specific(P＜0.05).Conclusion Many kinds of his-tone lysine methyltransferases and demethylases were regulated by both TGF-β1/Smad and TGF-β1/non-Smad signaling pathway in BMSCs bone differentiation.
何建伟;晏春艳;杨宗树;高永昌;蒋雯;方钦正;戴晓琴;曹薇薇
832000 新疆石河子,石河子大学第一附属医院检验中心832000 新疆石河子,石河子大学第一附属医院药学部832000 新疆石河子,石河子大学第一附属医院医学影像中心830000 新疆乌鲁木齐,新疆维吾尔自治区人民医院疼痛诊疗中心832000 新疆石河子,石河子大学第一附属医院关节外科832000 新疆石河子,石河子大学新疆地方与民族高发病教育部重点实验室
基础医学
骨髓间充质干细胞成骨分化组蛋白甲基化酶TGF-β1/Smad信号通路
bone marrow mesenchymal stem cells(BMSCs)osteogenic differentiationhistone methylasetransforming growth factor β1(TGF-β1)Smad signaling pathway
《中华骨质疏松和骨矿盐疾病杂志》 2024 (002)
123-130 / 8
石河子大学校级科研项目(ZZZC202142);石河子大学第一附属医院博士课题(BS202105);兵团科技计划项目(2022ZD035)
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