Effects of NCL Knockdown on Fibroblast-Like Synoviocytes

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation, synovial hyperplasia, and the destruction of bone and cartilage. Despite the use of various immunosuppressive disease-modifying antirheumatic drugs (DMARDs), a considerable proportion of RA patients remain symptomatic. As RA progresses, fibroblast-like synoviocytes (FLSs) undergo a phenotypic transition to an aggressive state, making them attractive non-immune cellular targets for RA treatment. However, there are currently no clinically available therapies that selectively ablate RA-FLSs due to the lack of specific molecular targets. Our research focuses on the knockdown of the nucleolin (NCL) gene in RA-FLSs. NCL is expressed in the cell of RA-FLSs and plays a crucial role in their aggressive transition. By specifically knocking down NCL, we observed significant inhibition of the harmful phenotypes exhibited by RA-FLSs. To investigate whether NCL plays a critical role in the tumor-like transformation and overactivation of RA-FLSs, we established an RA-FLSs line in which the target gene was silenced down by shRNA