title: MiR-23a inhibited IL-17-mediated proinflammatory mediators expression via targeting IKKα in articular chondrocytes.
abstract: The inflammatory cytokine interleukin 17 (IL-17) is an important contributor of rheumatoid arthritis (RA) chronicity. Although several microRNAs (miRNAs) have been shown to regulate RA pathogenesis, the function of miRNAs in articular chondrocytes during rheumatoid arthritis pathogenesis is unclear. Here we showed that miR-23a was downregulated in articular cartilage tissues from rheumatoid arthritis patients. MiR-23a suppressed IL-17 inflammatory cytokine-induced NF-κB activation and several proinflammatory mediators expression, such as cytokine IL-6, chemokine MCP-1, and matrix metalloproteinase MMP-3 in articular chondrocytes. Furthermore, we found that the miR-23a expression was inversely correlated with IKKα expression in articular cartilage tissues from rheumatoid arthritis patients. We identified that IKKα was the direct target of miR-23a and miR-23a inhibited IL-17-mediated proinflammatory mediators expression via targeting the IKKα in primary articular chondrocytes. Together, our study provides the first evidence of a role for miR-23a regulated IL-17-mediated proinflammatory mediators expression in rheumatoid arthritis by directly targeting IKKα. Our findings provide novel evidence that may be useful for future studies exploring therapeutic approaches for rheumatoid arthritis by targeting miR-23a. Thus, miR-23a may be a common therapeutic target for rheumatoid arthritis.
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Junzheng
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Chenjun
authors.initials: C
authors.lastname: Zhai
authors.affiliation: Department of Hematology, Zhongda Hospital, Southeast University, Nanjing, China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Fei
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China. Electronic address: fanweimin@vip.sina.com.
authors.forename: Weimin
authors.initials: W
authors.lastname: Fan
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D002358:Cartilage, Articular / Q000473:pathology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D019902:Chondrocytes / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D058990:Molecular Targeted Therapy
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018836:Inflammation Mediators; D020381:Interleukin-17; D015850:Interleukin-6; C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D051550:I-kappa B Kinase; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3
keywords: Chondrocytes; IKKα; Interleukin 17; Rheumatoid arthritis; miR-23a