Systemic Lupus Erythematosus Stimulates Chondrocyte Pyroptosis to Aggravate Arthritis via Suppression of NRF-2/KEAP-1 and NF-κB Pathway

作者：Shuchao Shen, Xuliang Fang, Helou Zhang, Tingting Lang, Fangda Fu, Yu Du, Taotao Xu, Hongting Jin, Peijian Tong, Chengliang Wu, Changfeng Hu, Hongfeng Ruan · 发表于：Journal of Inflammation Research · 年份：2025 · DOI：10.2147/jir.s502800 · 被引用次数：5 · 研究领域：Inflammasome and immune disorders、Gout, Hyperuricemia, Uric Acid、Osteoarthritis Treatment and Mechanisms

Purpose: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by diverse clinical manifestations, including joint symptoms. Arthritis represents one of the earliest manifestations of SLE, profoundly affecting the quality of life for affected individuals, yet the underlying mechanisms of SLE-associated arthritis remain insufficiently investigated. The study aimed to investigate the impact of SLE exacerbation on arthritis using the MRL/ lpr mouse model, which closely mimics human SLE manifestations. Methods: In the present study, we evaluated the impact of SLE onset on knee joint degeneration by comparing arthritic phenotype and complex molecular alterations between 6 female 14-week-old MRL/ lpr mice, which manifest SLE, and MRL/ MpJ mice, which remain unaffected. Results: Our results demonstrated that MRL/ lpr mice exhibited a more severe arthritic phenotype compared to MRL/ MpJ mice, characterized by elevated Osteoarthritis Research Society International (OARSI) scores ( P < 0.01), disrupted extracellular matrix metabolism, impaired chondrocyte proliferation and increased apoptosis. Notably, inflammatory cytokines proteins such as IL-1β and TNF-α (both P < 0.01), IL-18 and IL-6 (both P < 0.05), were significantly increased in articular cartilage of MRL/ lpr mice, accompanied by increased expression of calcitonin gene-related peptide (CGRP) ( P < 0.05), NETRIN-1, and NESTIN (both P < 0.01), indicating that SLE promotes inflammation response and sensory ner...