细胞因子治疗骨关节炎的研究现状及应用前景

Research status and application prospect of cytokine therapy for osteoarthritis

背景:在骨关节炎的软骨退变过程中,以软骨细胞为靶点的细胞因子和信号通路起到了重要作用。目的:综述近年来与骨关节炎相关的细胞因子和信号通路的作用机制及治疗方式等最新研究进展,以期为将来探索新的治疗靶点和治疗方式作参考依据。方法:在中国知网、万方数据、维普、PubMed、Web of Science和MEDLINE数据库进行文献检索,并以“骨关节炎,细胞因子,信号通路,软骨细胞,炎症,治疗”作为中文检索词,以“osteoarthritis,cytokine,signal pathway,chondrocyte,inflammation,therapy”作为英文检索词,对最终纳入的60篇文献进行了归纳总结。结果与结论:(1)在目前的研究中认为骨关节炎具体机制尚不明确,大量研究表明骨关节炎与细胞因子和信号通路关系密切,是一个复杂的作用过程,以细胞因子和信号通路作为治疗突破口的相关研究也是当前的热点。(2)白细胞介素1等促炎因子的受体拮抗剂对于骨关节炎治疗效果不佳,已有更多的学者开始进行基因治疗方式的研究。(3)目前关于转化生长因子β等细胞因子和Wnt信号通路的重组因子、基因治疗和间充质干细胞等治疗方式均获得了积极的研究成果,但其安全性和有效性等问题还需进一步的基础和临床研究验证。(4)目前相关的骨关节炎治疗方式如富血小板血浆疗法已广泛应用于临床,而重组因子疗法、基因治疗和间充质干细胞治疗均处于研究阶段,其中间充质干细胞治疗和基因治疗有望在软骨修复和再生领域做出突破,是值得期待的治疗方式,但其有效性和安全性尚需进一步研究,未来需探寻其作用机制和适用范围以制定标准。

BACKGROUND:In cartilage degeneration in osteoarthritis,cytokines and signaling pathways that target chondrocytes play an important role.OBJECTIVE:To review the latest research progress of osteoarthritis related cytokines and signaling pathways in recent years,such as the mechanism of action and treatment modalities,in order to provide a basis for future exploration of new therapeutic targets and modalities.METHODS:Literature search was conducted on CNKI,WanFang,VIP,PubMed,Web of Science,and Medline databases.Chinese search terms were“osteoarthritis,cytokines,signal pathway,chondrocyte,inflammation,treatment”.Finally,60 papers were included for review.RESULTS AND CONCLUSION:(1)In current studies,it is believed that the specific mechanism of osteoarthritis is not clear,and a large number of studies have shown that osteoarthritis is strongly associated with cytokines and signaling pathways,which is a complex process of action.Relevant studies taking cytokines and signaling pathways as therapeutic breakthroughs are also the current hot spot.(2)The receptor antagonists of pro-inflammatory factors such as interleukin 1 are not effective in the treatment of osteoarthritis,and more studies turn to gene therapy.(3)The therapeutic methods of transforming growth factorβ,recombinant factors of Wnt signaling pathway,gene therapy and mesenchymal stem cells have obtained positive research results.However,basic and clinical studies on safety and efficacy are likely to be conducted in future studies.(4)At present,relevant therapeutic methods such as platelet-rich plasma have been widely used in clinical practice,while recombinant factor,gene therapy and mesenchymal stem cell therapy are all in the research stage,among which mesenchymal stem cell therapy and gene therapy are expected to make breakthroughs in the field of cartilage repair and regeneration,and are worthy of expectation in the future.However,more clinical and basic studies are needed to verify its effectiveness and safety,explore its mechanism of action and scope of application,and set standards for its clinical use.