miR-204-5p inhibits inflammation of synovial fibroblasts in osteoarthritis by suppressing FOXC1 |
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| Institution: | 1. The Joint Surgical Center, Chenzhou No. 1 People''s Hospital, Chenzhou, Hunan, 423000, PR China;2. Pediatric Intensive Care Unit, Chenzhou No. 1 People''s Hospital, Chenzhou, Hunan, 423000, PR China;1. Department of Orthopaedic Surgery, Chungbuk National University Hospital, Chungbuk National University, Cheongju, Republic of Korea;2. Department of Orthopaedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;3. Department of Orthopaedic Surgery, Kangwon National University Hospital, Gangwon-Do, Republic of Korea;1. Department of Orthopaedic Surgery, National Hospital Organization Kyoto Medical Center, Japan;2. Applied Medical Engineering Science, Yamaguchi University Graduate School of Medicine, Japan;1. Department of Orthopedics, The First Affiliated Hospital of Xi’an Jiao Tong University, No. 277 Yanta West Road, Xi''an, Shaanxi 710061, People’s Republic of China;2. School of Public Health, Health Science Center of Xi’an Jiaotong University, NHC Key Laboratory of Trace Elements and Endemic Diseases (Xi’an Jiaotong University), Xi’an, Shaanxi No. 76 Yanta West Road, Xi’an 710061, People’s Republic of China;3. Department of Integrative Medical Biology, University of Umeå, Umeå, Sweden;1. Department of Orthopedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China;2. Department of Sports Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People''s Hospital, Shenzhen 518035, Guangdong, China;3. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China;4. Department of Thyroid and Breast Surgery, Shenzhen Breast Tumor Research Center for Diagnosis and Treatment, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People''s Hospital, Shenzhen 518035, Guangdong, China;5. Department of Clinical Medicine, Xiangya School of Medicine of Central South University, Changsha 518035, Hunan, China |
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| Abstract: | BackgroundThe paper is aimed at uncovering the mechanism of miR-204-5p in regulating inflammatory responses of human osteoarthritic synovial fibroblasts (SFs).MethodsIL-1β-induced osteoarthritic SFs were established as an osteoarthritis (OA) cell model. The osteoarthritic SFs were accordingly transfected with mimics-miR-204-5p, inhibitors-miR-204-5 or FOXC1 siRNA. MTT tested the vitality of osteoarthritic SFs by analyzing the cell optical density. The expressions of miR-204-5p, FOXC1, TNF-α, IL-6, PGE2, MMP-1, MMP-13 and COX-2 in osteoarthritic SFs were measured by qRT-PCR, Western blotting and/or ELISA. The binding of miR-204-5p to FOXC1 was verified through luciferase reporter assay. The regulatory effect of miR-204-5p on FOXC1 was also tested in normal SFs.ResultsmiR-204-5p was under-expressed and FOXC1 was over-expressed in osteoarthritic SFs. The expressions of FOXC1, TNF-α, IL-6, PGE2, MMP-1, MMP-13 and COX-2 were up-regulated in IL-1β-treated SFs. Up-regulation of miR-204-5p or down-regulation of FOXC1 suppressed the inflammatory responses of osteoarthritic SFs. miR-204-5p negatively regulated FOXC1 by being a sponge in osteoarthritic SFs as well as in normal SFs.ConclusionmiR-204-5p down-regulates FOXC1 to ameliorate inflammation of SFs in OA. |
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