Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China.
Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, China.
Mediators Inflamm. 2023 Jan 4;2023:2936236. doi: 10.1155/2023/2936236. eCollection 2023.
Osteoarthritis (OA) is considered a metabolic disorder. This study investigated the effect of resveratrol (RES) on cholesterol accumulation in osteoarthritic articular cartilage via the silent information regulator 1 (SIRT1)/forkhead transcription factor (FoxO1) pathway. Interleukin (IL)-1-treated chondrocytes that mimic OA chondrocytes were used in experiments. The optimal RES concentration was selected based on the results of chondrocyte proliferation in the Cell Counting Kit-8 assay. Western blotting, immunofluorescence, and reverse transcription-quantitative polymerase chain reaction were performed. For the animal experiments, mice were randomly divided into the RES group ( = 15), medial meniscus destabilization group ( = 15), and sham group ( = 15), and each group received the same dose of RES or saline. Articular cartilage tissue was obtained eight weeks after surgery for relevant histological analysis. Clinical tissue test results suggest that downregulation of the SIRT1/FoxO1 pathway is associated with cholesterol buildup in OA chondrocytes. For the studies, RES increased the expression of SIRT1 and phosphorylation of FoxO1 in IL-1-treated chondrocytes, promoted the expression of cholesterol efflux factor liver X receptor alpha (LXR), and inhibited the expression of cholesterol synthesis-associated factor sterol-regulatory element binding proteins 2 (SREBP2). This reduced IL-1-induced chondrocytes cholesterol accumulation. SIRT1 inhibition prevented the RES-mediated reduction in cholesterol buildup. Inhibiting but not reduced phosphorylation and increased cholesterol buildup in cultured chondrocytes. Additionally, experiments have shown that RES can alleviate cholesterol buildup and pathological changes in OA cartilage. Our findings suggest that RES regulates cholesterol buildup in osteoarthritic articular cartilage via the SIRT1/FoxO1 pathway, thereby improving the progression of OA.
骨关节炎（OA）被认为是一种代谢紊乱。本研究通过沉默信息调节因子 1（SIRT1）/叉头转录因子（FoxO1）通路研究白藜芦醇（RES）对骨关节炎关节软骨胆固醇积累的影响。采用白细胞介素（IL）-1处理的软骨细胞模拟 OA 软骨细胞进行实验。根据细胞计数试剂盒-8 测定软骨细胞增殖的结果选择最佳的 RES 浓度。进行 Western blot、免疫荧光和逆转录定量聚合酶链反应。在动物实验中，将小鼠随机分为 RES 组（n = 15）、内侧半月板不稳定组（n = 15）和假手术组（n = 15），每组给予相同剂量的 RES 或生理盐水。手术后 8 周获取关节软骨组织进行相关组织学分析。临床组织检测结果表明，SIRT1/FoxO1 通路下调与 OA 软骨细胞中胆固醇堆积有关。在RES 组，RES 增加了 IL-1 处理的软骨细胞中 SIRT1 的表达和 FoxO1 的磷酸化，促进了胆固醇流出因子肝 X 受体α（LXR）的表达，并抑制了胆固醇合成相关因子固醇调节元件结合蛋白 2（SREBP2）的表达，从而减少了 IL-1 诱导的软骨细胞胆固醇积累。SIRT1 抑制阻止了 RES 介导的胆固醇堆积减少。抑制但不减少培养的软骨细胞中的磷酸化并增加胆固醇堆积。此外，实验表明 RES 可以减轻 OA 软骨中的胆固醇堆积和病理变化。我们的研究结果表明，RES 通过 SIRT1/FoxO1 通路调节骨关节炎关节软骨中的胆固醇积累，从而改善 OA 的进展。
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