CD142+ synovial fibroblast drives meniscus destruction in rheumatoid arthritis

Abstract Rheumatoid arthritis (RA) induced destruction of knee joints is a common cause of total knee arthroplasty (TKA). Although previous evidence suggests that bone and cartilage damage is the main pathogenesis of RA joint destruction, the meniscus, a special structure in the knee joint, has been ignored. Here, we identified CD142 + synovial fibroblasts as a novel SF sub-cluster located in the sublining layer in normal and osteoarthritis knee synovium, which is elevated and migrates to the lining layer (LL) in RA knee synovium. Intra-articular injection of CD142 + SF can quickly and drastically damage the meniscus but has a slight effect on cartilage. RNA sequencing revealed that ABCC4 was highly expressed in CD142 + SF, and the pharmacological blockade of ABCC4 by MK571 attenuated CD142 + SF-induced meniscal degradation. Long-term follow-up of the RA cohort indicated that enriched CD142 + SF in the LL was a risk factor for severe joint destruction and eventually underwent TKA. Our results demonstrate that CD142 + SF can be used as an indicator to assess prognosis and a therapeutic target to inhibit meniscal damage, thereby alleviating RA knee joint destruction.