Citation: | ZUO Shufei, LIANG Shu, QIN Yilu, WU Jie, ZHANG Chao, GUO Zhanfei, BIAN Caiyue, FAN Wenqiang. Effect and mechanism of mircoRNA-6779-5p on chondrocyte injury induced by interleukin-1β[J]. Journal of Clinical Medicine in Practice, 2023, 27(12): 69-75, 79. DOI: 10.7619/jcmp.20231173 |
To analyze the effects of microRNA-6779-5p (miR-6779-5p) on cell proliferation and apoptosis in chondrocyte stimulated by interleukin-1β (IL-1β) and the related molecular mechanism.
Expression level of RNA was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). CHON-001 cells were transfected with miR-6779-5p mimics, overexpression vector of interleukin-1 receptor associated kinase 3 (IRAK3) and their respective controls, and 10 ng/mL IL-1β was used to stimulate the cells. The effects of miR-6779-5p and IRAK3 on cell injury induced by IL-1β were analyzed by functional tests; the nuclear factor kappa B (NF-κB) pathway related protein expression was analyzed by Western blotting; the relationship between miR-6779-5p and IRAK3 was identified.
MiR-6779-5p expression was down-regulated in osteoarthritis patients, while IRAK3 expression was up-regulated (P < 0.05). MiR-6779-5p and IRAK3 expressions also showed the same trend in CHON-001 cells induced by IL-1β at differed concentrations (P < 0.05). IL-1β treatment decreased the activity (100.00% versus 51.00%) and EdU positive rate (43.00% versus 25.00%) of CHON-001 cells but increased cell apoptosis rate (6.43% versus 18.60%) (P < 0.05), however, these effects were alleviated after miR-6779-5p overexpression (cell viability: 52.00% versus 85.00%; the positive rate of EdU: 25.67% versus 38.67%; cell apoptosis rate: 18.70% versus 12.10%, P < 0.05). In addition, miR-6779-5p targeted IRAK3. The up-regulation of IRAK3 expression could reverse the effects of miR-6779-5p overexpression on CHON-001 cells (P < 0.05). Moreover, miR-6779-5p mimics reduced the p-P65-to-P65 ratio (2.06 versus 1.34) and the p-IκBα-to-IκBα ratio (2.42 versus 1.42) in IL-1β-induced chondrocytes (P < 0.05), but IRAK3 overexpression mitigated these effects (p-P65-to-P65 ratio: 1.30 versus 1.88; p-IκBα-to-IκBα ratio: 1.45 versus 2.16, P < 0.05).
MiR-6779-5p can ameliorate chondrocyte injury induced by IL-1β by inhibiting the activation of IRAK3/NF-κB pathway, which suggests that miR-6779-5p might be a potential target for the treatment of osteoarthritis.
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