二甲双胍
医学
内科学
内分泌学
骨关节炎
瘦素
炎症
细胞凋亡
脂肪组织
脂联素
渗透(HVAC)
促炎细胞因子
滑膜炎
关节炎
病理
胰岛素
胰岛素抵抗
化学
生物化学
热力学
物理
肥胖
替代医学
作者
Delong Li,Guangfeng Ruan,Yan Zhang,Yang Zhao,Zhaohua Zhu,Q. Ou,Hong Huang,Jieli Chen,Weiyu Han,Su’an Tang,Jia Li,Liang Wang,Tianyu Chen,Xiaochun Bai,Daozhang Cai,Changhai Ding
出处
期刊:Rheumatology
[Oxford University Press]
日期:2022-08-19
卷期号:62 (4): 1652-1661
被引量:22
标识
DOI:10.1093/rheumatology/keac467
摘要
To investigate the therapeutic effect and mechanism of metformin on knee OA in normal diet (ND) mice or high-fat diet (HFD)-induced obese mice.Destabilization of the medial meniscus surgery was performed in ND mice or HFD mice, and metformin was administrated in drinking water or not. The changes of OA joint structure, infiltration and polarization of synovial macrophages and circulating and local levels of leptin and adiponectin were evaluated. In vitro, the effects of metformin on chondrocytes and macrophages, and of conditioned mediums derived from mouse abdominal fat on murine chondrogenic cell line ATDC5 and murine macrophage cell line RAW264.7, were detected.Metformin showed protective effects on OA, characterized by reductions on OARSI score [2.00, 95% CI (1.15, 2.86) for ND mice and 3.17, 95% CI (2.37, 3.96) for HFD mice] and synovitis score [1.17, 95% CI (0.27, 2.06) for ND mice and 2.50, 95% CI (1.49, 3.51) for HFD mice] after 10 weeks of treatment, and the effects were more significant in HFD mice than in ND mice. Mechanistically, in addition to decreasing apoptosis and matrix-degrading enzymes expression in chondrocytes as well as infiltration and pro-inflammatory differentiation of synovial macrophages, metformin reduced leptin secretion by adipose tissue in HFD mice.Metformin protects against knee OA which could be through reducing apoptosis and catabolism of chondrocytes, and suppressing infiltration and pro-inflammatory polarization of synovial macrophages. For obese mice, metformin has a greater protective effect in knee OA additionally through reducing leptin secretion from adipose tissue.
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