PDF(Pubmed)
Abstract：
Rheumatoid arthritis is an autoimmune disorder that causes chronic joint pain, swelling, and movement impairment, resulting from prolonged inflammation-induced cartilage and bone degradation. The pathogenesis of RA, which is still unclear, makes diagnosis and treatment difficult and calls for new therapeutic strategies to cure the disease. Recent research has identified FPRs as a promising druggable target, with AMC3, a novel agonist, showing preclinical efficacy in vitro and in vivo. In vitro, AMC3 (1-30 µM) exhibited significant antioxidant effects in IL-1β (10 ng/mL)-treated chondrocytes for 24 h. AMC3 displayed a protective effect by downregulating the mRNA expression of several pro-inflammatory and pro-algic genes (iNOS, COX-2, and VEGF-A), while upregulating genes essential for structural integrity (MMP-13, ADAMTS-4, and COLIAI). In vivo, AMC3 (10 mg kg-1) prevented hypersensitivity and restored postural balance in CFA-injected rats after 14 days. AMC3 attenuated joint alterations, reduced joint inflammatory infiltrate, pannus formation, and cartilage erosion. Chronic AMC3 administration reduced transcriptional changes of genes causing excitotoxicity and pain (EAATs and CCL2) and prevented morphological changes in astrocytes, including cell body hypertrophy, processes length, and thickness, caused by CFA in the spinal cord. This study demonstrates the usefulness of AMC3 and establishes the groundwork for further research.
摘要：
类风湿性关节炎是一种导致慢性关节痛的自身免疫性疾病，肿胀,和运动损伤，由长时间的炎症引起的软骨和骨降解引起。RA的发病机制,目前还不清楚，这使得诊断和治疗变得困难，需要新的治疗策略来治愈这种疾病。最近的研究已经确定FPR是一个有希望的药物靶标，与AMC3，一种新的激动剂，在体外和体内显示临床前功效。体外，AMC3（1-30µM）在IL-1β（10ng/mL）处理的软骨细胞中表现出24小时的显着抗氧化作用。AMC3通过下调几种促炎和促发基因（iNOS，COX-2和VEGF-A），同时上调结构完整性必需的基因(MMP-13、ADAMTS-4和COLIAI)。在体内,14天后，AMC3（10mgkg-1）可预防注射CFA的大鼠的超敏反应并恢复姿势平衡。AMC3减弱关节改变，减少关节炎症浸润，血管nus形成,和软骨侵蚀。慢性AMC3给药减少了引起兴奋性毒性和疼痛的基因（EAAT和CCL2）的转录变化，并阻止了星形胶质细胞的形态变化，包括细胞体肥大，进程长度，和厚度，由脊髓中的CFA引起。这项研究证明了AMC3的有用性，并为进一步的研究奠定了基础。
