Cell子刊：孔祥英/鲁超团队发现类风湿性关节炎治疗新靶点

Core Insights - The study identifies Mesothelin (MSLN) as a biomarker and potential therapeutic target for bone destruction in rheumatoid arthritis (RA) [4][8] - MSLN levels are significantly elevated in RA patients and collagen-induced arthritis (CIA) animal models, indicating its role in disease pathology [6][9] Group 1: Research Findings - MSLN is involved in various biological processes, particularly in regulating immune responses, but its role in osteoclastogenesis is not well understood [6] - Inhibition of MSLN through pharmacological and genetic methods significantly impairs osteoclast differentiation and bone resorption [6] - Downregulation of MSLN in animal models effectively reduces bone destruction [6] Group 2: Mechanism of Action - MSLN interacts directly with PI3K, leading to the activation of the PI3K/AKT signaling pathway, which promotes the expression and translocation of NFATc1, thereby facilitating osteoclast differentiation [6][9] - MSLN is upregulated in the synovial tissue and plasma of RA patients, driving osteoclast differentiation and mediating pathological bone destruction [9] Group 3: Implications for Treatment - Targeting MSLN may represent a novel therapeutic strategy for addressing bone destruction associated with rheumatoid arthritis [8][9]