Downregulation of MicroRNA-495 Alleviates IL-1ß Responses among Chondrocytes by Preventing SOX9 Reduction.
Yonsei Med J
; 62(7): 650-659, 2021 Jul.
Article
em En
| MEDLINE
| ID: mdl-34164963
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-1ß (IL-1ß, 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-1ß-treated TC28a2 cells and chondrocytes from damaged cartilage tissues of patients with OA. Anti-miR-495 abolished the effect of IL-1ß in TC28a2 cells and rescued the protein levels of SOX9 and COL2A1, which were reduced by IL-1ß. 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-1ß-treated TC28a2 cells. CONCLUSION: We demonstrated that inhibition of miRNA-495 alleviates IL-1ß-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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Base de dados:
MEDLINE
Assunto principal:
Condrócitos
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MicroRNAs
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Interleucina-1beta
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Fatores de Transcrição SOX9
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article