Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, China.
Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China.
J Orthop Surg Res. 2023 May 26;18(1):386. doi: 10.1186/s13018-023-03872-9.
Knee osteoarthritis (KOA) is a disability-associated condition that is rapidly growing with the increase in obesity rates worldwide. There is a pressing need for precise management and timely intervention in the development of KOA. L-carnitine has been frequently recommended as a supplement to increase physical activity in obese individuals due to its role in fatty acid metabolism, immune disorders, and in maintaining the mitochondrial acetyl-CoA/CoA ratio. In this study, we aimed to investigate the anti-inflammatory effects of L-carnitine on KOA and delineate a potential molecular mechanism.
Lipopolysaccharide-stimulated primary rat fibroblast-like synoviocytes (FLS) were treated with an AMP-activated protein kinase (AMPK) inhibitor or siRNA and carnitine palmitoyltransferase 1 (CPT1) siRNA to examine the synovial protective effects of L-carnitine. An anterior cruciate ligament transection model of rats was treated with an AMPK agonist (metformin) and CPT1 inhibitor (etomoxir) to define the therapeutic effects of L-carnitine.
L-carnitine displayed a protective effect against synovitis of KOA in vitro and in vivo experiments. Specifically, L-carnitine treatment can reduce synovitis by inhibiting AMPK-ACC-CPT1 pathway activation and showed an increase in fatty acid β-oxidation, a lower lipid accumulation, and a noticeable improvement in mitochondrial function.
Our data suggested that L-carnitine can mitigate synovitis in FLS and synovial tissue, and the underlying mechanism may be related to improving mitochondrial function and reducing lipid accumulation via the AMPK-ACC-CPT1 signaling pathway. Therefore, L-carnitine may be a potential treatment strategy for KOA.
膝骨关节炎（KOA）是一种与残疾相关的疾病，随着全球肥胖率的增加，其发病率迅速上升。迫切需要对 KOA 的发展进行精确的管理和及时的干预。由于其在脂肪酸代谢、免疫紊乱和维持线粒体乙酰辅酶 A/辅酶 A 比中的作用，左旋肉碱经常被推荐作为增加肥胖个体身体活动的补充剂。在这项研究中，我们旨在研究左旋肉碱对 KOA 的抗炎作用，并阐明其潜在的分子机制。
用 AMP 激活蛋白激酶（AMPK）抑制剂或 siRNA 和肉毒碱棕榈酰转移酶 1（CPT1）siRNA 处理脂多糖刺激的原代大鼠成纤维样滑膜细胞（FLS），以研究左旋肉碱对滑膜的保护作用。用 AMPK 激动剂（二甲双胍）和 CPT1 抑制剂（乙莫克舍）治疗大鼠前交叉韧带切断模型，以确定左旋肉碱的治疗效果。
左旋肉碱在体外和体内实验中均显示出对 KOA 滑膜炎的保护作用。具体来说，左旋肉碱治疗可通过抑制 AMPK-ACC-CPT1 通路的激活来减轻滑膜炎，并显示出脂肪酸β氧化增加、脂质积累减少和线粒体功能明显改善。
我们的数据表明，左旋肉碱可以减轻 FLS 和滑膜组织中的滑膜炎，其潜在机制可能与通过 AMPK-ACC-CPT1 信号通路改善线粒体功能和减少脂质积累有关。因此，左旋肉碱可能是 KOA 的一种潜在治疗策略。
