Osteoarthritis (OA) is a degenerative joint disease affecting millions of people worldwide. In OA, chondrocytes, synovial cells and other joint cells become activated when exposed to an abnormal environment, including mechanical stress, inflammatory cytokines or disorganization of matrix proteins. Several analogues of the hormones called incretins have been developed and are used notably for treating type 2 diabetes mellitus. Data has accumulated to suggest that incretinomimetics, which bind to the glucagon-like peptide-1 receptor (GLP-1R), have beneficial pleiotropic effects such as immunomodulation, anti-inflammation and neuronal protection. Thus, because of their anti-inflammatory properties, GLP-1-based therapies could benefit OA patients. This review focuses on the GLP-1R pathway, molecular mechanisms and phenotypes related to OA pathogenesis. The translational potential of this article The search for new therapeutic targets to treat people suffering from OA remains urgent as there is currently no disease-modifyingtherapy available for this disease. This review discusses how GLP-1 analogues could be potential DMOADs for treating OA thanks to their anti-inflammatory, immunoregulatory and differentiation properties.

中文翻译：

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靶向 GLP-1/GLP-1R 轴治疗骨关节炎：新机会？

骨关节炎 (OA) 是一种退行性关节疾病，影响全世界数百万人。在 OA 中，软骨细胞、滑膜细胞和其他关节细胞在暴露于异常环境（包括机械应力、炎症细胞因子或基质蛋白解体）时会被激活。几种称为肠降血糖素的激素类似物已被开发出来，主要用于治疗 2 型糖尿病。积累的数据表明，与胰高血糖素样肽-1 受体 (GLP-1R) 结合的肠降血糖素模拟物具有有益的多效性作用，例如免疫调节、抗炎和神经元保护。因此，由于其抗炎特性，基于 GLP-1 的疗法可以使 OA 患者受益。本综述重点讨论与 OA 发病机制相关的 GLP-1R 通路、分子机制和表型。本文的转化潜力 寻找新的治疗靶点来治疗 OA 患者仍然紧迫，因为目前还没有针对这种疾病的疾病缓解疗法。本综述讨论了 GLP-1 类似物如何因其抗炎、免疫调节和分化特性而成为治疗 OA 的潜在 DMOAD。