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Int Arch Allergy Immunol ; 182(5): 408-416, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33147588

RESUMO

INTRODUCTION: Osteoarthritis (OA) is a common musculoskeletal disease characterized by pain, stiffness, limited activity, occasional effusion, and local inflammation. MiR-146 is one of the noncoding RNA closely related to OA, but the role of miR-146 in OA remains controversial. The tumour necrosis factor receptor OX40 is activated by its cognate ligand OX40L (TNFSF4) and functions as a T-cell costimulatory molecule. The T-cell functions, including cytokine production, expansion, and survival, are enhanced by the OX40 costimulatory signals. METHODS: We established an inflammatory model of condylar chondrocytes induced by IL-1ß and TNF-α and detected the expression of miRNA by miRNA sequencing. Then, cell transfection was used to study the role of miR146a-5p in OA. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and database analysis were used to screen out potential target genes of miR-146a-5p. A dual luciferase activity assay tested whether ox40l is the target gene of miR-146a-5p. RESULTS: MiR-146a-5p and OX40L was upregulated after induced by IL-1ß and TNF-α, miR-146a-5p reduced the production of inflammatory factors but had no effect on chondrophenotypic factors, and ox40l was targeted by miR-146a-5p. CONCLUSION: OX40L and miR-146a-5p of condylar chondrocytes in the inflammatory environment (induced by IL-1ß and TNF-α) were significantly increased, miR-146a-5p is a protective factor in the inflammatory response, which can reduce the production of inflammatory factors, and miR-146a-5p may regulate T-cell-mediated immunity through targeting of ox40l in OA.


Assuntos
Condrócitos/metabolismo , Regulação da Expressão Gênica , Interleucina-1beta/metabolismo , Ligante OX40/genética , Osteoartrite/genética , Osteoartrite/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Condrócitos/patologia , Biologia Computacional/métodos , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Humanos , Ligante OX40/metabolismo , Osteoartrite/patologia
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