Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
International UNESCO center for Health Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran.
J Cell Biochem. 2022 Aug;123(8):1285-1297. doi: 10.1002/jcb.30309. Epub 2022 Jul 27.
Osteoarthritis (OA) is a progressive joint disease. The etiology of OA is considered to be multifactorial. Currently, there is no definitive treatment for OA, and the existing treatments are not very effective. Hypercholesterolemia is considered a novel risk factor for the development of OA. Statins act as a competitive inhibitor of the β-hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase and are widely used to manage hypercholesterolemia. Inhibition of HMG-CoA reductase results in reduced synthesis of a metabolite named mevalonate, thereby reducing cholesterol biosynthesis in subsequent steps. By this mechanism, statins such as atorvastatin and simvastatin could potentially have a preventive impact on joint cartilage experiencing osteoarthritic deterioration by reducing serum cholesterol levels. Atorvastatin can protect cartilage degradation following interleukin-1β-stimulation. Atorvastatin stimulates the STAT1-caspase-3 signaling pathway that was shown to be responsible for its anti-inflammatory effects on the knee joint. Simvastatin had chondroprotective effects on OA in vitro by reducing matrix metalloproteinases expression patterns. In this study, we tried to review the therapeutic effects of statins on OA.
骨关节炎(OA)是一种进行性关节疾病。OA 的病因被认为是多因素的。目前,OA 没有明确的治疗方法,现有的治疗方法效果不是很好。高胆固醇血症被认为是 OA 发展的一个新的危险因素。他汀类药物作为β-羟-β-甲基戊二酰辅酶 A(HMG-CoA)还原酶的竞争性抑制剂,被广泛用于治疗高胆固醇血症。HMG-CoA 还原酶的抑制导致名为甲羟戊酸的代谢物的合成减少,从而减少后续步骤中的胆固醇生物合成。通过这种机制,阿托伐他汀和辛伐他汀等他汀类药物可以通过降低血清胆固醇水平,对经历骨关节炎恶化的关节软骨产生潜在的预防作用。阿托伐他汀可以保护软骨降解后白介素-1β刺激。阿托伐他汀刺激 STAT1-caspase-3 信号通路,这被证明是其对膝关节抗炎作用的原因。辛伐他汀通过降低基质金属蛋白酶表达模式对 OA 具有体外软骨保护作用。在这项研究中,我们试图综述他汀类药物对 OA 的治疗作用。