METTL14通过m6a依赖性USP7 mRNA的稳定促进人骨髓基质细胞的成骨分化。

IF 2.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yu Leng, Zhiwen Liu, Jun Min, Qing Ke, Yiqing Shao, Junyan Lai, Jing Zhao
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引用次数: 0

摘要

骨质疏松症(Osteoporosis, OP)是临床上常见的非应力性骨折高发的骨骼疾病,是危害中老年妇女健康和生命的主要退行性疾病之一。人骨髓干细胞(hBMSCs)异常分化和功能的机制尚不清楚。采用3-(4,5)-二甲基噻吩偶氮(-z-y1)-3,5-二苯四氮唑胺(MTT)法、碱性磷酸酶(ALP)染色、茜素红染色检测细胞增殖和分化情况。利用生物信息学方法、荧光素酶测定、RNA免疫沉淀(RIP)和免疫沉淀(IP)预测并验证了胰岛素样生长因子2 mrna结合蛋白2 (IGF2BP2)和泛素特异性蛋白酶7 (USP7)之间的相互作用。放线菌素D处理检测各组mRNA的稳定性。甲基转移酶样14 (METTL14)表达在成骨分化培养基诱导的hBSMCs中增加,并与增强的成骨分化有关。METTL14通过调节n6 -甲基腺苷(m6A)水平调控USP7的表达。IGF2BP2对USP7 mRNA的稳定性发挥m6a依赖性作用,USP7通过增强SIRT1去泛素化而增加hBMSCs中SIRT1 (SIRT1)的表达。METTL14通过m6A-IGF2BP2-USP7通路刺激hBMSCs成骨分化,通过SIRT1-Bmi1信号通路促进hBMSCs成骨发育。METTL14通过稳定USP7 mRNA以m6a依赖的方式刺激hBMSCs的成骨分化。IGF2BP2也稳定了USP7,并调节下游SIRT1-Bmi1信号。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
METTL14 Promotes the Osteogenic Differentiation of Human Bone Marrow Stromal Cells via m6A-Dependent Stabilization of USP7 mRNA.

Osteoporosis (OP) is a common clinical bone disease that can cause a high incidence of non-stress fractures and is one of the main degenerative diseases that endangers the health and life of middle-aged and older women. The mechanism underlying the abnormal differentiation and function of human bone marrow stem cells (hBMSCs) remains to be elucidated. Cell proliferation and differentiation were determined using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, alkaline phosphatase (ALP) staining, and Alizarin Red Staining. The interaction between insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and ubiquitin-specific protease 7 (USP7) was predicted and validated using bioinformatics approaches, luciferase assays, RNA immunoprecipitation (RIP), and immunoprecipitation (IP). Actinomycin D treatment was used to test the stability of mRNA in the various groups. Methyltransferase-like 14 (METTL14) expression was increased in osteogenic differentiation medium-induced hBSMCs and was associated with enhanced osteogenic differentiation. METTL14 regulated the expression USP7 by modulating its N6-methyladenosine (m6A) level. IGF2BP2 exerted an m6A-dependent effect on USP7 mRNA stability and USP7 increased sirtuin 1 (SIRT1) expression in hBMSCs by enhancing SIRT1 deubiquitination. METTL14 stimulated the osteogenic differentiation of hBMSCs through the m6A-IGF2BP2-USP7 pathway and promoted hBMSCs osteogenic development via SIRT1-Bmi1 signaling. METTL14 stimulated the osteogenic differentiation of hBMSCs by stabilizing USP7 mRNA in an m6A-dependent manner. USP7 was also stabilized by IGF2BP2 and it regulated downstream SIRT1-Bmi1 signaling.

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来源期刊
Biochemical Genetics
Biochemical Genetics 生物-生化与分子生物学
CiteScore
3.90
自引率
0.00%
发文量
133
审稿时长
4.8 months
期刊介绍: Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.
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