Department of Medicine, University of California, San Diego, California.
Am J Physiol Cell Physiol. 2022 Jun 1;322(6):C1061-C1067. doi: 10.1152/ajpcell.00086.2022. Epub 2022 Apr 27.
Rheumatoid arthritis (RA) is a common autoimmune disease that causes inflammation of the joints and damage to the cartilage and bone. The pathogenesis of RA is characterized in many patients by the presence of antibodies against citrullinated proteins. Proteoglycans are key structural elements of extracellular matrix in the joint articular cartilage and synovium and are secreted as lubricants in the synovial fluid. Alterations of proteoglycans contribute to RA pathogenesis. Proteoglycans such as aggrecan can be citrullinated and become potential targets of the rheumatoid autoimmune response. Proteoglycans are also upregulated in RA joints and/or undergo alterations of their regulatory functions over cytokines and chemokines, which promotes inflammation and bone damage. Recent studies have aimed to not only clarify these mechanisms but also develop novel proteoglycan-modulating therapeutics. These include agents altering the function and signaling of proteoglycans as well as tolerizing agents targeting citrullinated aggrecan. This mini-review summarizes the most recent findings regarding the dysregulation of proteoglycans that contributes to RA pathogenesis and the potential for proteoglycan-modulating agents to improve upon current RA therapy.
类风湿关节炎（RA）是一种常见的自身免疫性疾病，可引起关节炎症和软骨及骨损伤。许多 RA 患者的发病机制表现为存在针对瓜氨酸化蛋白的抗体。蛋白聚糖是关节软骨和滑膜中细胞外基质的关键结构元素，作为滑液中的润滑剂分泌。蛋白聚糖的改变有助于 RA 的发病机制。聚集蛋白聚糖等蛋白聚糖可以瓜氨酸化，成为类风湿自身免疫反应的潜在靶点。蛋白聚糖在 RA 关节中也上调，或改变其对细胞因子和趋化因子的调节功能，从而促进炎症和骨损伤。最近的研究旨在不仅阐明这些机制，而且开发新的蛋白聚糖调节治疗方法。这些方法包括改变蛋白聚糖功能和信号的药物以及针对瓜氨酸化聚集蛋白聚糖的耐受药物。这篇综述总结了最近关于蛋白聚糖失调导致 RA 发病机制的研究结果，以及蛋白聚糖调节药物改善当前 RA 治疗的潜力。
