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| 破骨细胞在类风湿关节炎致骨破坏病理变化中的作用及其调控 |
| Function and regulation of the osteoclast in the pathological changes of bone destruction in rheumatoid arthritis |
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| DOI： |
| 中文关键词: 破骨细胞 类风湿关节炎 骨破坏 细胞因子 |
| 英文关键词:Osteoclasts Ｒheumatoid arthritis Bone destruction Cytokines |
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| 中文摘要: |
| 类风湿关节炎(ＲA)是一种严重的慢性自身免疫性炎症性疾病，关节软骨及骨破坏是 ＲA 的主要病理变化，是患者致残的主要原因。破骨细胞(OC)在 ＲA 骨破坏的病理过程中起关键作用，其调控依赖于 OC 形成、分化及活化的过程。巨噬细胞、滑膜成纤维细胞等是 OC 形成的主要来源，促炎性细胞因子在这个过程中起重要作用。主要的是 ＲANK/ＲANKL/OPG、M-CSF、TNF、IL-1 和 IL-17，这些细胞因子通过不同的信号传导通路促进 OC 的成熟及分化;此外，有些细胞因子对 OC 的分化及骨吸收作用产生负性调控作用，如 IL-27、IL-4、IL-10、IFN-γ，大部分细胞因子通过 ＲANK/ＲANKL/OPG 系统，直接或间接作用于 OC，两者之间的平衡决定骨破坏的结局。这些细胞因子通过多条信号传导通路介导 OC 对骨破坏的调控作用，其中NFATc1 是关键的调节因子，如 ＲANKL 通过 NF-κB/AP-1/c-fos 和钙离子信号通路两条信号通路，调节 NFATc1 的活化，促进OC 分化;TNF 通过激活 NF-κB，JNK 和 p38 通路，活化 NFATc1 促进 OC 形成，还包括MAPK、STAT 等通路。深入了解 OC 的病理过程及骨形成和骨吸收机制，监测及干扰促进 OC 活化的细胞因子，为早期 ＲA 的治疗提供新的靶点。 |
| 英文摘要: |
| Ｒheumatoid arthritis (ＲA) is a severe chronic systemic autoimmune disease． Destruction of articular cartilage and bone is the main pathological changes of ＲA，which is the main cause of disability in patients． Osteoclasts (OC) play a key role in the pathological process in bone destruction of ＲA． The regulation depends on the formation，differentiation，and activation of OC．Macrophages and synovial fibroblasts are the main source of osteoclastogenesis． Proinflammatory cytokines play an important role in this process． The main cytokines are ＲANK/ＲANKL/OPG，M-CSF，TNF，IL-1，and IL-17． They promote the maturation and differentiation of OC through different pathways of signal transduction． In addition，some cytokines have negative effects on the differentiation and bone resorption of OC，such as IL-27，IL-4，IL-10，IFN-γ，and so on． Most cytokines function through ＲANK/ ＲANKL/OPG system in a direct or indirect manner． The balance between these two types of cytokines determines the outcome of bone destruction． These cytokines mediate the role of OC in the regulation of bone destruction through multiple signal transduction pathways． NFATc1 is a key regulator． The activation of NFATc1 is regulated by ＲANKL in two ways，the NF-κB/AP-1/c-fos pathway and calcium signaling，resulting in the activation of OC． TNF activates NFATc1 to promote the formation of OC through activation of NF-κB，JNK，and p38 pathways． Other pathways include MAPK and STAT． In depth understanding of the pathological process of OC and the mechanism of bone formation and resorption，monitoring and intervening the cytokines of OC
activation，may provide new targets for the treatment of early ＲA． |
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