破骨细胞(OCs)的异常活化是类风湿关节炎（RA）骨破坏的核心机制，抑制OCs分化，阻止骨侵蚀进程，是目前RA治疗的主要目标之一。课题组前期研究发现，髓系来源的抑制性细胞(MDSCs)在RA中具有重要的促炎作用，且具有分化为OCs的潜能；抑制CaN/NFAT信号通路能显著抑制MDSCs分化为OCs。既往的研究表明中药青藤碱（SIN）具有良好的抑制RA骨破坏作用，但SIN能否通过抑制CaN/NFAT信号通路，阻止MDSCs分化为OCs，缓解关节炎骨破坏尚有待进一步研究。本研究拟建立胶原诱导性关节炎(CIA)模型，通过病理学、免疫学和分子生物学等实验手段，探讨SIN干预对CIA MDSCs分化为OCs的作用及机制；建立MDSCs体外培养，SIN及CaN/NFAT信号通路抑制剂干预细胞模型，进一步阐明SIN干预对MDSCs分化为OCs的作用及机制，为RA骨破坏防治和新药研发提供新思路和理论依据。

Abnormal activation of osteoclasts (OCs) is the core mechanism of bone destruction in rheumatoid arthritis (RA). The suppression of OCs differentiation and bone erosion is the one of the main objectives of treatment. Our previous research indicated that myeloid-derived suppressor cells (MDSCs) had a critical pro-inflammatory role, and could potentially differentiate into OCs. And our studies also suggested that the counts of OCs derived from MDSCs declined obviously by inhibiting calcineurin/nuclear factor of activated T cell (CaN/NFAT) signaling pathway. Additionally, it has been reported that sinomenine (SIN) could significantly restrain bone destruction, but further research is need to clarify whether SIN suppresses differentiation of MDSCs into functional OCs by inhibiting CaN/NFAT signaling pathway. In the light of the above, our project will establish collagen-induced arthritis (CIA) model, and investigate the influence of MDSCs and their OCs differentiation potential, and also reveal the mechanisms after intervention by SIN using pathology, immunology or molecular biology techniques. On the other hand, we will also establish a model of MDSCs polarization in vitro, and further confirm the mechanisms of MDSCs differentiation into OCs after intervention by SIN or CaN/NFAT signaling pathway inhibitor. In conclusion, we expect to explicit the new idea on suppression of bone destruction by SIN, and provide theoretical foundation for the drug development of RA.