Abstract. The present study aimed to investigate the effect and underlying mechanism of microRNA (miR)-4262 in the development of osteoarthritis (OA) in rats. Primary chondrocytes were separated from Sprague-Dawley rats and then treated with tumor necrosis factor-α (TNF-α). The level of miR-4262 was detected in TNF-α-treated chondrocytes, and then the miR-4262 or its target gene sirtuin type 1 (SIRT1) level was overexpressed, or knocked down. Furthermore, cell viability, cell apoptosis, cell autophagy and matrix synthesis, as well as the expressions of proteins associated with the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway were detected. miR-4262 was significantly overexpressed in TNF-α-treated chondrocytes compared with untreated cells (P<0.05). TNF-α treatment or miR-4262 overexpression significantly decreased cell viability, autophagy-related proteins levels and matrix synthesis-related proteins levels, as well as increased the apoptotic rate in chondrocytes (P<0.05). Overexpression of SIRT1 significantly increased cell viability, autophagy-related proteins levels and matrix synthesis-related proteins levels, as well as decreased the apoptotic rate in TNF-α-treated chondrocytes (P<0.05). In addition, the effects of miR-4262 on cell viability, cell apoptosis, cell autophagy and matrix synthesis were inhibited by SIRT1 (P<0.05). Furthermore, upregulated miR-4262 remarkably increased the expressions of phosphorylated (p)-PI3K, p-AKT and p-mTOR (P<0.05) in TNF-α treated chondrocytes. The present study revealed that the upregulation of miR-4262 may promote the occurrence and development of OA in rats by regulating cell viability, cell apoptosis, cell autophagy, and matrix synthesis. Furthermore, these roles of miR-4262 may be associated with PI3K/AKT/mTOR signaling pathway.

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Background: Osteoarthritis (OA) is a common subtype of arthritis with prevalence increase with age, and is characterized by the degeneration of articular cartilage. Chondrocytes play curial role in the formation of the articular cartilage. This work aimed to figure out the effect of miR-200a/b in chondrocytes of OA, as well as the underlying molecular mechanism. Methods: Cell viability, apoptosis, pro-inflammatory factors secretion, and matrix degradation were detected with cell counting kit-8 (CCK-8), flow cytometry, enzyme-linked immunosorbent assay (ELISA), and western blotting, separately. Expression of miR-200a/b and fucosyltransferase 4 (FUT4) was measured by RT-qPCR (RNA level) and western blot (protein level). The relationship between miR-200a/b and FUT4 was verified by dual-luciferase assay and RNA immunoprecipitation (RIP) assay. Results: Interleukin 1β (IL-1β) induced OA cell model in primary chondrocytes ex-vivo, as evidenced by cell viability inhibition, apoptosis rate promotion, and IL-6 and tumor necrosis factor α (TNF-α) resection enhancement, as well as Collegen 2a1 (Col2a1) and Aggrecan expression inhibition. Expression of miR-200a/b was downregulated in knee articular cartilage of OA patients and IL-1β-induced primary chondrocytes. miR-200a/b overexpression decreased IL-1β-induced cell injuries, which was further blocked by FUT4 upregulation. Mechanically, FUT4 was negatively regulated by miR-200a/b via target binding. Conclusion: miR-200a/b could alleviate IL-1β-induced chondrocyte injuries via targeting its downstream gene FUT4, suggesting that miR-200a/b-FUT4 axis might be a potential candidate to the treatment of OA.