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Downregulation of MicroRNA-495 Alleviates IL-1β Responses among Chondrocytes by Preventing SOX9 Reduction

 Soyeong Joung  ;  Dong Suk Yoon  ;  Sehee Cho  ;  Eun Ae Ko  ;  Kyoung Mi Lee  ;  Kwang Hwan Park  ;  Jin Woo Lee  ;  Sung Hwan Kim 
 YONSEI MEDICAL JOURNAL, Vol.62(7) : 650-659, 2021-07 
Journal Title
Issue Date
Cells, Cultured ; Chondrocytes* / metabolism ; Down-Regulation ; Humans ; Interleukin-1beta* / metabolism ; MicroRNAs* / genetics ; SOX9 Transcription Factor* / genetics ; SOX9 Transcription Factor* / metabolism
Chondrocytes ; SOX9 ; inflammation ; miRNA-495 ; osteoarthritis
Purpose: Our previous work demonstrated that miRNA-495 targets SOX9 to inhibit chondrogenesis of mesenchymal stem cells. In this study, we aimed to investigate whether miRNA-495-mediated SOX9 regulation could be a novel therapeutic target for osteoarthritis (OA) using an in vitro cell culture model. Materials and methods: An in vitro model mimicking the OA environment was established using TC28a2 normal human chondrocyte cells. Interleukin-1β (IL-1β, 10 ng/mL) was utilized to induce inflammation-related changes in TC28a2 cells. Safranin O staining and glycosaminoglycan assay were used to detect changes in proteoglycans among TC28a2 cells. Expression levels of COX-2, ADAMTS5, MMP13, SOX9, CCL4, and COL2A1 were examined by qRT-PCR and/or Western blotting. Immunohistochemistry was performed to detect SOX9 and CCL4 proteins in human cartilage tissues obtained from patients with OA. Results: miRNA-495 was upregulated in IL-1β-treated TC28a2 cells and chondrocytes from damaged cartilage tissues of patients with OA. Anti-miR-495 abolished the effect of IL-1β in TC28a2 cells and rescued the protein levels of SOX9 and COL2A1, which were reduced by IL-1β. SOX9 was downregulated in the damaged cartilage tissues of patients with OA, and knockdown of SOX9 abolished the effect of anti-miR-495 on IL-1β-treated TC28a2 cells. Conclusion: We demonstrated that inhibition of miRNA-495 alleviates IL-1β-induced inflammatory responses in chondrocytes by rescuing SOX9 expression. Accordingly, miRNA-495 could be a potential novel target for OA therapy, and the application of anti-miR-495 to chondrocytes could be a therapeutic strategy for treating OA.
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Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sung Hwan(김성환) ORCID logo https://orcid.org/0000-0001-5743-6241
Park, Kwang Hwan(박광환) ORCID logo https://orcid.org/0000-0002-2110-0559
Yoon, Dong Suk(윤동석) ORCID logo https://orcid.org/0000-0001-5945-5569
Lee, Kyoung Mi(이경미) ORCID logo https://orcid.org/0000-0002-9038-8162
Lee, Jin Woo(이진우) ORCID logo https://orcid.org/0000-0002-0293-9017
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