Role of miR-101a in targeting Cox-2 to attenuate chondrocyte hypertrophic differentiation and osteoarthritis progressionOA
MicroRNAs(miRNAs)are small non-coding RNAs that regulate gene expression post-transcriptionally,often playing critical roles in various biological processes,Recent studies have highlighted the involvement of miRNAs in chondrogenesis by targeting key marker genes,Among these,miR-101a has been identified as a significant regulator,previously reported to target cyclooxygenase-2(Cox-2,ptgs2)in various contexts,Here,we investigate the role of miR-101a in chondrocyte hypertrophy and osteoarthritis(OA)progression,focusing on its regulation of Col10a1 expression,Using multiple web-based tools(TargetScan,PicTar,miRDB,and miRCODE),we identified miR-101a as a potential regulator of Col10a1,Our in vitro experiments demonstrated that miR-101a was down-regulated during chondrocyte hypertrophy in MCT and ATDC5 cells,while Col10a1 and Cox-2 expression levels were up-regulated,Overexpression of miR-101a via mimics resulted in a significant decrease in Col10a1 and Cox-2 at both mRNA and protein levels,whereas inhibition of miR-101a led to their up-regulation,Additionally,MMP-13 protein levels were reduced upon miR-101a overexpression,with no significant changes in Sox9 and Runx2 expression,Luciferase reporter assays confirmed that Cox-2 was a direct target of miR-101a,suggesting that miR-101a indirectly regulates Col10a1 expression via Cox-2,In vivo,intra-articular injection of miR-101a mimics in a medial meniscus-induced OA mouse model resulted in decreased Col10a1 expression and reduced articular damage,supporting the protective role of miR-101a in OA progression,Our findings highlight miR-101a as a negative regulator of chondrocyte hypertrophy through Cox-2,and could be a potential target for further exploration in OA therapy.
Rui Mi;Jinnan Chen;Tianxiang Zhu;Huiqin Bian;Rong Wei;Rushuang Deng;Tiaotiao Han;Qian Wang;Yaojuan Lu;Longwei Qiao;Yuting Liang;Qiping Zheng
Department of Hematology and Hematological Laboratory Science,Jiangsu Key Laboratory of Medical Science and Laboratory Medicine,School of Medicine,Jiangsu University,Zhenjiang,Jiangsu 212013,China Department of Clinical Laboratory,Wuxi Ninth People''s Hospital Affiliated to Soochow University,Wuxi,Jiangsu 214000,ChinaDepartment of Hematology and Hematological Laboratory Science,Jiangsu Key Laboratory of Medical Science and Laboratory Medicine,School of Medicine,Jiangsu University,Zhenjiang,Jiangsu 212013,ChinaDepartment of Hematology and Hematological Laboratory Science,Jiangsu Key Laboratory of Medical Science and Laboratory Medicine,School of Medicine,Jiangsu University,Zhenjiang,Jiangsu 212013,ChinaDepartment of Hematology and Hematological Laboratory Science,Jiangsu Key Laboratory of Medical Science and Laboratory Medicine,School of Medicine,Jiangsu University,Zhenjiang,Jiangsu 212013,ChinaDepartment of Hematology and Hematological Laboratory Science,Jiangsu Key Laboratory of Medical Science and Laboratory Medicine,School of Medicine,Jiangsu University,Zhenjiang,Jiangsu 212013,ChinaDepartment of Hematology and Hematological Laboratory Science,Jiangsu Key Laboratory of Medical Science and Laboratory Medicine,School of Medicine,Jiangsu University,Zhenjiang,Jiangsu 212013,ChinaDepartment of Hematology and Hematological Laboratory Science,Jiangsu Key Laboratory of Medical Science and Laboratory Medicine,School of Medicine,Jiangsu University,Zhenjiang,Jiangsu 212013,ChinaDepartment of Hematology and Hematological Laboratory Science,Jiangsu Key Laboratory of Medical Science and Laboratory Medicine,School of Medicine,Jiangsu University,Zhenjiang,Jiangsu 212013,China Department of Human Anatomy,School of Medicine,Jiangsu University,Zhenjiang,Jiangsu 212013,ChinaDepartment of Hematology and Hematological Laboratory Science,Jiangsu Key Laboratory of Medical Science and Laboratory Medicine,School of Medicine,Jiangsu University,Zhenjiang,Jiangsu 212013,China Shenzhen International Institute for Biomedical Research,Shenzhen,Guangdong 518110,China Shenzhen Walgenron Bio-Pharm Co.,Ltd.,Shenzhen,Guangdong 518118,ChinaThe Affiliated Suzhou Hospital of Nanjing Medical University,Nanjing,Jiangsu 215008,China The Molecular Oncology Laboratory,Department of Orthopedic Surgery and Rehabilitation Medicine,The University of Chicago Medical Center,Chicago,IL 60637,USAThe Molecular Oncology Laboratory,Department of Orthopedic Surgery and Rehabilitation Medicine,The University of Chicago Medical Center,Chicago,IL 60637,USA Center for Clinical Laboratory,The First Affiliated Hospital of Soochow University,Suzhou,Jiangsu 215000,ChinaDepartment of Hematology and Hematological Laboratory Science,Jiangsu Key Laboratory of Medical Science and Laboratory Medicine,School of Medicine,Jiangsu University,Zhenjiang,Jiangsu 212013,China Shenzhen International Institute for Biomedical Research,Shenzhen,Guangdong 518110,China Shenzhen Walgenron Bio-Pharm Co.,Ltd.,Shenzhen,Guangdong 518118,China The Molecular Oncology Laboratory,Department of Orthopedic Surgery and Rehabilitation Medicine,The University of Chicago Medical Center,Chicago,IL 60637,USA
医药卫生
Chondrocyte differentiationCol10a1Cox-2miR-101aOsteoarthritis
《Genes & Diseases》 2026 (3)
P.428-441,14
supported by the Jiangsu Provincial Key Research and Development Program(No.BE2020679 to Q.Z.)the Innovation Team(leader)of Jiangsu Province,China(2017,to Q.Z.)Science Foundation of Jiangsu Province(China)(No.BK20240371 to Y.L.)the National Science Foundation of China(No.81901632 to Y.L.,82001576 to L.Q.).
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