Sun Hao, Lin Xiaobin, Liu Fangzhou, Zhang Yingbin, Ma Jianda, Huang Zhencheng, Huang Junming, Yao Lutian, Zhang Mengyuan, Chen Meiyi, Xu Jie, Wei Yulong, Dai Lie, Ma Ruofan
Department of Joint Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Department of Rheumatology and Immunology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Nat Commun. 2025 Jul 28;16(1):6942. doi: 10.1038/s41467-025-61842-7.
Previous evidence suggest bone and cartilage damage is the main pathogenesis of rheumatoid arthritis joint destruction. However, the role of meniscus usually has not been thoroughly explored. Here, we identify CD142 synovial fibroblasts as a subset located at sublining layer in normal and osteoarthritis synovium, which is increased and distributed at lining layer in rheumatoid arthritis synovium. Injection of CD142 fibroblasts into DBA/1 male mice's knee destructs meniscus but has slight effect on cartilage. ABCC4 is highly expressed in CD142 fibroblasts, whose blockage by MK571 attenuates CD142 fibroblasts-induced meniscus destruction through cAMP/PKA signaling. Long-term follow-up of rheumatoid arthritis cohort indicates that enriched CD142 fibroblasts at lining layer are a risk factor for severe knee joint destruction and eventually undergo total knee arthroplasty. Our results demonstrate CD142 fibroblasts as an indicator to assess prognosis and a therapeutic target to inhibit meniscal destruction, thereby alleviating rheumatoid arthritis knee joint damage.
先前的证据表明，骨和软骨损伤是类风湿性关节炎关节破坏的主要发病机制。然而，半月板的作用通常尚未得到充分研究。在此，我们鉴定出CD142滑膜成纤维细胞是正常和骨关节炎滑膜中位于滑膜下层的一个亚群，在类风湿性关节炎滑膜中该亚群数量增加并分布于滑膜表层。将CD142成纤维细胞注射到DBA/1雄性小鼠膝关节会破坏半月板，但对软骨影响较小。ABCC4在CD142成纤维细胞中高表达，MK571对其进行阻断可通过cAMP/PKA信号传导减弱CD142成纤维细胞诱导的半月板破坏。对类风湿性关节炎队列的长期随访表明，滑膜表层中富集的CD142成纤维细胞是严重膝关节破坏的危险因素，最终会接受全膝关节置换术。我们的结果表明，CD142成纤维细胞可作为评估预后的指标以及抑制半月板破坏的治疗靶点，从而减轻类风湿性关节炎膝关节损伤。
