Department of Anatomy, Baqai Medical University, Karachi, Pakistan.
Biomedical Research Center, Department of Biomedical & Biological Sciences, Sohail University, Karachi, Pakistan.
Clin Exp Rheumatol. 2024 Nov;42(11):2258-2264. doi: 10.55563/clinexprheumatol/t3mejo. Epub 2024 Jul 15.
Metabolic factors play significant role in the natural history of knee osteoarthritis (KO). There is a limited understanding of molecular and cellular events that give rise to the disease in patients. This study explored the possible cellular mechanisms by which metabolic syndrome leads to KO.
This cross-sectional study enrolled 80 subjects with KO who fulfilled the ACR diagnostic criteria and were undergoing total knee replacement surgery. The patients were divided into two groups: KO patients without metabolic syndrome and KO patients with metabolic syndrome.
We hypothesised that metabolic syndrome may accelerate pathogenesis of OA by enhanced RAGE axis in articular cartilage and Infrapatellar fat pad of the knee joint. We have found enhanced protein expression of receptor for advanced glycation end products (RAGE) and its ligands AGEs and HMGB-1 in knee joint tissue of KO patients with metabolic syndrome as compared to KO patients without metabolic syndrome. Further downstream, the gene expression of oxidative stress regulators such as NADPH and inflammation, NFĸB were upregulated in KO patients with MetS as compared to KO patients alone. Higher levels of advanced oxidation products and inflammatory marker IL-17 were exhibited in synovial fluid of KO patients with metabolic syndrome. The enhanced levels of these oxidative stress and inflammatory markers were reflected in the serum of KO patients with metabolic syndrome as well.
We conclude that enhanced function of RAGE axis could be one of the mechanisms by which metabolic syndrome leads to KO.
代谢因素在膝关节骨关节炎（KO）的自然病程中起着重要作用。人们对导致患者患病的分子和细胞事件的了解有限。本研究探讨了代谢综合征导致 KO 的可能细胞机制。
这项横断面研究纳入了 80 名符合 ACR 诊断标准并接受全膝关节置换手术的 KO 患者。患者分为两组：无代谢综合征的 KO 患者和有代谢综合征的 KO 患者。
我们假设代谢综合征可能通过增强关节软骨和膝关节髌下脂肪垫中的 RAGE 轴加速 OA 的发病机制。与无代谢综合征的 KO 患者相比，我们发现代谢综合征 KO 患者的关节组织中 RAGE 及其配体 AGEs 和 HMGB-1 的蛋白表达增强。进一步下游，氧化应激调节剂如 NADPH 和炎症的 NFκB 的基因表达在 MetS 的 KO 患者中上调，与单独 KO 患者相比。代谢综合征 KO 患者的滑液中显示出更高水平的高级氧化产物和炎症标志物 IL-17。代谢综合征 KO 患者的血清中也反映了这些氧化应激和炎症标志物的增强水平。
我们得出结论，RAGE 轴的增强功能可能是代谢综合征导致 KO 的机制之一。
