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Long non-coding RNA Gm37494 alleviates osteoarthritis chondrocyte injury via the microRNA-181a-5p/GABRA1 axis
OBJECTIVE: This study was conducted to investigate the effect of long non-coding RNA (lncRNA) Gm37494 on osteoarthritis (OA) and its related molecular mechanism. METHODS: The cartilage tissues were obtained from OA patients, and an OA mouse model was induced by the destabilization of the medial meni...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185876/ https://www.ncbi.nlm.nih.gov/pubmed/35689264 http://dx.doi.org/10.1186/s13018-022-03202-5 |
Sumario: | OBJECTIVE: This study was conducted to investigate the effect of long non-coding RNA (lncRNA) Gm37494 on osteoarthritis (OA) and its related molecular mechanism. METHODS: The cartilage tissues were obtained from OA patients, and an OA mouse model was induced by the destabilization of the medial meniscus, followed by measurement of Gm37494, microRNA (miR)-181a-5p, GABRA1 mRNA, and the encoded GABA(A)R(α1) protein expression. Thereafter, a cellular model was induced by interleukin-1β (IL-1β) treatment in chondrocytes, followed by ectopic and silencing experiments. Chondrocyte proliferation was detected by CCK-8 and EdU assays, chondrocyte apoptosis by flow cytometry and western blot, and the levels of inflammatory factors by ELISA. The binding of Gm37494 to miR-181a-5p was evaluated by dual-luciferase reporter gene and RIP assays, and that of GABRA1 to miR-181a-5p by dual-luciferase reporter gene and RNA pull-down assays. RESULTS: OA patients and mice had decreased GABRA1 mRNA and GABA(A)R(α1) protein levels and elevated miR-181a-5p expression in cartilage tissues. Additionally, Gm37494 was poorly expressed in OA mice. Mechanistically, Gm37494 directly bound to and inversely modulated miR-181a-5p that negatively targeted GABRA1. In IL-1β-induced chondrocytes, Gm37494 overexpression enhanced cell proliferation and suppressed cell apoptosis and inflammation, whereas further miR-181a-5p up-regulation or GABRA1 silencing abolished these trends. CONCLUSIONS: Conclusively, Gm37494 elevated GABRA1 expression by binding to miR-181a-5p, thus ameliorating OA-induced chondrocyte damage. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13018-022-03202-5. |
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