Mechanism of bone and cartilage deterioration in rheumatoid arthritis via RANKL/Fas signaling

本研究以人类风湿性关节炎（RA）动物模型MRL/lpr小鼠为研究对象，研究Fas基因突变小鼠破骨细胞（OCs）的功能。体外和体内实验表明，MRL/lpr OCs作为抗原呈递细胞活化外周T细胞的功能增强。此外，MRL/lpr OCs对S1 P的迁移反应显著增强。MRL/lpr小鼠OCs功能亢进在RA骨破坏的发病机制中起重要作用。OCs的Fas信号通路可调节OCs的分化、活化和迁移。

In this study, we investigated the functions of osteoclasts (Ocs) from MRL/lpr mice, animal model for human rheumatoid arthritis (RA), bearinf a mutant of Fas gene. In vitro and in vivo experiments showed enhanced function of MRL/lpr Ocs as antigen-presenting cells to activate peripheral T cells. Furthermore, the migratory response of MRL/lpr Ocs to S1P was significantly enhanced. The hyperfunctions of Ocs in MRL/lpr mice play a potent role in the pathogenesis for RA with bone destruction. Fas signaling of Ocs may regulate the differentiation, activation, and migration of Ocs.