Mechanisms of miR-21-5p in Promoting Osteoarthritis Progression through Inhibition of SIRT2/AKT Signaling Pathway

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

doi:10.12259/j.issn.2095-610X.S20260404

Volume 47 Issue 4

Apr. 2026

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Xiaotian CHEN, Zhenfei DING, Yining SONG, Banghong JIANG, Fan ZHANG, Yi GAO, Jianzhong GUAN. Mechanisms of miR-21-5p in Promoting Osteoarthritis Progression through Inhibition of SIRT2/AKT Signaling Pathway[J]. Journal of Kunming Medical University, 2026, 47(4): 30-39. doi: 10.12259/j.issn.2095-610X.S20260404

Citation:

Xiaotian CHEN, Zhenfei DING, Yining SONG, Banghong JIANG, Fan ZHANG, Yi GAO, Jianzhong GUAN. Mechanisms of miR-21-5p in Promoting Osteoarthritis Progression through Inhibition of SIRT2/AKT Signaling Pathway[J]. Journal of Kunming Medical University, 2026, 47(4): 30-39. doi: 10.12259/j.issn.2095-610X.S20260404

Citation:

Xiaotian CHEN, Zhenfei DING, Yining SONG, Banghong JIANG, Fan ZHANG, Yi GAO, Jianzhong GUAN. Mechanisms of miR-21-5p in Promoting Osteoarthritis Progression through Inhibition of SIRT2/AKT Signaling Pathway[J]. Journal of Kunming Medical University, 2026, 47(4): 30-39. doi: 10.12259/j.issn.2095-610X.S20260404

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Mechanisms of miR-21-5p in Promoting Osteoarthritis Progression through Inhibition of SIRT2/AKT Signaling Pathway

doi: 10.12259/j.issn.2095-610X.S20260404

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，Bengbu Anhui 233000
3.
College of Pharmacy，Bengbu Medical University，Bengbu Anhui 233000
4.
Department of Plastic Surgery，First Affiliated Hospital of Bengbu Medical University，Bengbu Anhui 233000，China

Received Date: 2025-09-06
Available Online: 2025-12-10
Publish Date: 2026-04-28

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)

References

[1]	赵奎, 潘润桑, 蓝奉军, 等. 骨关节炎中自噬与凋亡相互作用的分子机制[J]. 中国组织工程研究, 2024, 28(18): 2912-2917. doi: 10.12307/2024.058
[2]	Xia B, Di C, Zhang J, et al. Osteoarthritis pathogenesis: A review of molecular mechanisms[J]. Calcif Tissue Int, 2014, 95(6): 495-505. doi: 10.1007/s00223-014-9917-9
[3]	Iwakawa HO, Tomari Y. The Functions of microRNAs: mRNA decay and translational repression[J]. Trends Cell Biol, 2015, 25(11): 651-665.
[4]	Luan J, Che G, Man G, et al. Ginsenoside Rb1 from Panax ginseng attenuates monoiodoacetate-induced osteoarthritis by inhibiting miR-21-5p/FGF18-mediated inflammation[J]. J Food Biochem, 2022, 46(10): e14340.
[5]	Ma S, Zhang A, Li X, et al. miR-21-5p regulates extracellular matrix degradation and angiogenesis in TMJOA by targeting Spry1[J]. Arthritis Res Ther, 2020, 22(1): 99. doi: 10.1186/s13075-020-2145-y
[6]	Qin L, Yang J, Su X, et al. The miR-21-5p enriched in the apoptotic bodies of M2 macrophage-derived extracellular vesicles alleviates osteoarthritis by changing macrophage phenotype[J]. Genes Dis, 2022, 10(3): 1114-1129.
[7]	Zhu H, Yan X, Zhang M, et al. miR-21-5p protects IL-1β-induced human chondrocytes from degradation[J]. J Orthop Surg Res, 2019, 14(1): 118. doi: 10.1186/s13018-019-1160-7
[8]	Qu Z A, Ma X J, Huang S B, et al. SIRT2 inhibits oxidative stress and inflammatory response in diabetic osteoarthritis[J]. Eur Rev Med Pharmacol Sci, 2020, 24(6): 2855-2864.
[9]	Yang Q, Zhou Y, Cai P, et al. Downregulation of microRNA-23b-3p alleviates IL-1β-induced injury in chondrogenic CHON-001 cells[J]. Drug Des Devel Ther, 2019, 13: 2503-2512. doi: 10.2147/DDDT.S211051
[10]	Shen K, Wang X, Wang Y, et al. miR-125b-5p in adipose derived stem cells exosome alleviates pulmonary microvascular endothelial cells ferroptosis via Keap1/Nrf2/GPX4 in sepsis lung injury[J]. Redox Biol, 2023, 62: 102655. doi: 10.1016/j.redox.2023.102655
[11]	Kong R, Ji L, Pang Y, et al. Exosomes from osteoarthritic fibroblast-like synoviocytes promote cartilage ferroptosis and damage via delivering microRNA-19b-3p to target SLC7A11 in osteoarthritis[J]. Front Immunol, 2023, 14: 1181156. doi: 10.3389/fimmu.2023.1181156
[12]	Zhang A, Ma S, Yuan L, et al. Knockout of miR-21-5p alleviates cartilage matrix degradation by targeting Gdf5 in temporomandibular joint osteoarthritis[J]. Bone Joint Res, 2020, 9(10): 689-700. doi: 10.1302/2046-3758.910.BJR-2020-0140.R1
[13]	Liu B, Xian Y, Chen X, et al. Inflammatory fibroblast-like synoviocyte-derived exosomes aggravate osteoarthritis via enhancing macrophage glycolysis[J]. Adv Sci, 2024, 11(14): 2307338. doi: 10.1002/advs.202307338
[14]	Mrosewski I, Jork N, Gorte K, et al. Regulation of osteoarthritis-associated key mediators by TNFα and IL-10: Effects of IL-10 overexpression in human synovial fibroblasts and a synovial cell line[J]. Cell Tissue Res, 2014, 357(1): 207-223. doi: 10.1007/s00441-014-1868-y
[15]	Rodrigues P M, Afonso M B, Simão A L, et al. miR-21-5p promotes NASH-related hepatocarcinogenesis[J]. Liver Int, 2023, 43(10): 2256-2274. doi: 10.1111/liv.15682
[16]	Xue J, Liu J, Xu B, et al. miR-21-5p inhibits inflammation injuries in LPS-treated H9c2 cells by regulating PDCD4[J]. Am J Transl Res, 2021, 13(10): 11450-11460.
[17]	庾珊, 肖林, 龚东平, 等. 抑制miR-153-3p通过调控Nrf2延缓椎间盘退变的调节机制[J]. 昆明医科大学学报, 2025, 46(5): 21-29. doi: 10.12259/j.issn.2095-610X.S20250503
[18]	Hu Q, Ecker M. Overview of MMP-13 as a promising target for the treatment of osteoarthritis[J]. Int J Mol Sci, 2021, 22(4): 1742. doi: 10.3390/ijms22041742
[19]	Gan D, Tao C, Jin X, et al. Piezo1 activation accelerates osteoarthritis progression and the targeted therapy effect of artemisinin[J]. J Adv Res, 2024, 62: 105-117. doi: 10.1016/j.jare.2023.09.040
[20]	Zhuang H, Ren X, Jiang F, et al. Indole-3-propionic acid alleviates chondrocytes inflammation and osteoarthritis via the AhR/NF-κB axis[J]. Mol Med, 2023, 29(1): 17. doi: 10.1186/s10020-023-00614-9
[21]	Zhang Y, Wang X, Li X K, et al. Sirtuin 2 deficiency aggravates ageing-induced vascular remodelling in humans and mice[J]. Eur Heart J, 2023, 44(29): 2746-2759. doi: 10.1093/eurheartj/ehad381
[22]	Hu Z, Xu W, Yang X, et al. SIRT2 inhibition attenuates the vasculopathy and vision impairment via Akt signaling in retinopathy of prematurity[J]. Exp Eye Res, 2023, 233: 109547. doi: 10.1016/j.exer.2023.109547
[23]	Piracha Z Z, Saeed U, Kim J, et al. An alternatively spliced sirtuin 2 isoform 5 inhibits hepatitis B virus replication from cccDNA by repressing epigenetic modifications made by histone lysine methyltransferases[J]. J Virol, 2020, 94(16): e00926.
[24]	Ma J, Li X, Li Q, et al. Niacin regulates glucose metabolism and osteogenic differentiation via the SIRT2-C/EBPβ-AREG signaling axis[J]. Biomed Pharmacother, 2024, 180: 117447. doi: 10.1016/j.biopha.2024.117447
[25]	Qian B, Yang Y, Tang N, et al. M1 macrophage-derived exosomes impair beta cell insulin secretion via miR-212-5p by targeting SIRT2 and inhibiting Akt/GSK-3β/β-catenin pathway in mice[J]. Diabetologia, 2021, 64(9): 2037-2051. doi: 10.1007/s00125-021-05489-1
[26]	Yuan K, Wu Q, Yao Y, et al. Deacetylase SIRT2 inhibition promotes microglial M2 polarization through axl/PI3K/AKT to alleviate white matter injury after subarachnoid hemorrhage[J]. Transl Stroke Res, 2025, 16(4): 1075-1093. doi: 10.1007/s12975-024-01282-5

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