Mechanism of miR-21-5p in Promoting Osteoarthritis Progression Through Inhibition of the SIRT2/AKT Signaling Pathway

Xiaotian CHEN; Zhenfei DING; Yining SONG; Banghong JIANG; Fan ZHANG; Yi GAO; Jianzhong GUAN

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Article Navigation > Journal of Kunming Medical University > 2025 > Accepted Manuscript

Xiaotian CHEN, Zhenfei DING, Yining SONG, Banghong JIANG, Fan ZHANG, Yi GAO, Jianzhong GUAN. Mechanism of miR-21-5p in Promoting Osteoarthritis Progression Through Inhibition of the SIRT2/AKT Signaling Pathway[J]. Journal of Kunming Medical University.

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Mechanism of miR-21-5p in Promoting Osteoarthritis Progression Through Inhibition of the SIRT2/AKT Signaling Pathway

1.
Tissue Transplantation Key Laboratory of Anhui Province，Bengbu Medical University，Bengbu Anhui 233000
2.
Department of Orthopedics，The First Affiliated Hospital of Bengbu Medical University
3.
College of Pharmacy，Bengbu Medical University
4.
Department of Plastic Surgery，First Affiliated Hospital of Bengbu Medical University，Bengbu Anhui 233000，China

Abstract

Abstract

Objective To investigate the mechanism of miR-21-5p in promoting osteoarthritis （OA） progression by regulating the SIRT2/AKT signaling pathway. Methods An in vitro OA model was established by inducing human chondrocyte cell line CP-H107 with 10 ng/mL IL-1β. Experimental groups included: IL-1β + NC mimic, IL-1β + miR-21-5p mimic, IL-1β + NC inhibitor, IL-1β + miR-21-5p inhibitor, and IL-1β + miR-21-5p mimic + oe SIRT2. Expression levels of MMP13, SIRT2, AKT, and p-AKT were detected by RT-qPCR, Western blot （WB）, and immunofluorescence. Cell apoptosis was analyzed by Annexin V-FITC/PI flow cytometry. IL-6, TNF-α, and IL-10 levels were measured by ELISA. The direct interaction between miR-21-5p and SIRT2 was validated by a dual-luciferase reporter assay. Results Following IL-1β stimulation, miR-21-5p and MMP13 expression in CP-H107 cells were significantly elevated （P < 0.05）. miR-21-5p overexpression promoted MMP13 expression, cytokine （IL-6, TNF-α, IL-10） secretion, and cell apoptosis （P < 0.05）, while miR-21-5p inhibition produced opposite effects （P < 0.05）. Dual-luciferase reporter assays confirmed that miR-21-5p directly targets SIRT2. Overexpression of miR-21-5p significantly downregulated SIRT2 expression and reduced the p-AKT/AKT ratio （P < 0.05）. Further experiments demonstrated that SIRT2 overexpression partially reversed the MMP13 upregulation, inflammatory factor release, and increased apoptosis induced by miR-21-5p overexpression （P < 0.05）. Conclusion miR-21-5p promotes chondrocyte catabolism, inflammatory response, and apoptosis by targeting and inhibiting SIRT2, thereby blocking its regulatory effect on the AKT pathway and accelerating OA progression.
- miR-21-5p,
- SIRT2,
- AKT,
- Osteoarthritis

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References(26)

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