大量证据表明骨髓水肿是预测类风湿关节炎（RA）骨侵蚀的最强危险因素，炎症导致骨髓微环境异常而引起破骨细胞过度分化激活可能是主要原因，确切机制不明。我们大量原创工作证明新型细胞因子IL-29在RA中有较强促炎作用，且近期新发现RA患者血清IL-29含量与破骨细胞标志基因表达显著相关，胶原诱导关节炎小鼠（CIA）骨髓中IL-29特异性受体IL-28Rα表达显著高于正常鼠。基于我们的工作基础和最新发现，提出假说：IL-29是调节RA骨髓破骨细胞分化微环境的重要细胞因子。本研究以IL-28Rα基因敲除鼠、造血干细胞和髓系细胞特异性IL-28Rα基因敲除鼠、CIA小鼠为模型，利用MRI、MicroCT、EMSA、泛素化等技术从动物、细胞、分子层次，从骨髓微环境的独特视角揭示IL-29对RA骨侵蚀的作用及调控机制。研究成果将有助于发现IL-29新作用靶点及RA骨侵蚀新机制，为RA防治提供新思路。

Numerous studies have shown that the bone marrow edema is the strongest predictor of bone erosion for Rheumatoid arthritis (RA).The accelerated osteoclast activation in bone marrow caused by inflammation-mediated microenvironment might be an explanation, but the exact mechanism remains unclear. We previously reported that IL-29 may contribute to synovia inflammation during RA pathogenesis and play an important role in innate and adaptive immunity. In recent study, we found that IL-29 concentration in sera was associated with increased osteoclast differentation in RA patients, and the expression of IL-28Ra (the specific receptor of IL-29) in the bone marrow of CIA mice was significantly elevated compared to normal control. We therefore hypothesized that IL-29 plays a critical in regulation the microenvironment of osteoclast differentiation. Here we will empoly IL-28Rα knock out mice conditional knockout mice and CIA models, and MRI、MicroCT、EMSA、ubiquition and other techniques to investigate the effect and mechanism of IL-29 on RA bone erosion. Our results will not only help to understand the novel role of IL-29 but also facilitate the identification a novel idea to suppress RA bone erosion.