摘要
背景:骨关节炎的病理特征为关节软骨的逐渐退化和软骨下骨的异常变形。近年随着医学研究的深入,发现丝裂原活化蛋白激酶信号通路对炎症细胞浸润、炎症因子释放、软骨细胞增殖等方面具有调控作用,这对于治疗骨关节炎尤为重要。目的:就近年来丝裂原活化蛋白激酶信号通路调控骨关节炎相关机制的主要研究进展做简要概述,旨在为骨关节炎治疗提供新思路。方法:检索中国知网、万方、PubMed数据库,以“骨关节炎、骨关节病、骨关节炎病、关节退行性变、骨性关节炎,丝裂原激活蛋白激酶、MAPK、MAP激酶、MAPK通路、p38丝裂原活化蛋白激酶类、细胞外信号调节MAP激酶类以及JNK丝裂原活化蛋白激酶类”等为中文检索词,以“mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinases”等为英文检索词,检索2019年1月至2024年11月发表的相关文献,最终纳入108篇文章进行总结分析。结果与结论:①细胞内外的各种刺激会激活丝裂原活化蛋白激酶信号通路,进而调控基因转录和蛋白合成,促进肿瘤坏死因子α、白细胞介素1β、白细胞介素6等炎症因子的释放,这些炎症因子的释放加重了骨关节炎的进程;②以皂苷类和黄酮类为主的中药有效成分及以活血化瘀、补益肝肾为主要功效的中药复方和制剂,均可通过抑制丝裂原活化蛋白激酶信号通路来调控基质金属蛋白酶的释放、平衡成骨和破骨稳态、减轻滑膜炎症、减少炎症因子及炎症小体释放、减少焦亡、促进自噬、改善氧化应激等诸多方面对骨关节炎起治疗作用;③虽然中药凭借自身多成分、多靶点、多途径以及不良反应小等优势在骨关节炎治疗中成为热门,但针对个体骨关节炎进展程度运用好丝裂原活化蛋白激酶信号通路指导治疗是该项技术的难点,还需要不断的研究探索;④因此,进一步开发能调控丝裂原活化蛋白激酶信号通路的相关中药抑制剂可能是未来治疗骨关节炎一种潜在的药物策略。
BACKGROUND:Osteoarthritis is pathologically characterized by progressive degeneration of the articular cartilage and abnormal deformation of the subchondral bone.In recent years,with the deepening of medical research,it has been found that the mitogen-activated protein kinases(MAPK)signaling pathway has a regulatory role in inflammatory cell infiltration,inflammatory factor release,and chondrocyte proliferation,which is particularly important for the treatment of osteoarthritis.OBJECTIVE:To briefly review the main research progress in the mechanism of MAPK signaling pathway regulating osteoarthritis in recent years,aiming to provide new ideas for the treatment of osteoarthritis.METHODS:CNKI,WanFang and PubMed databases were searched for relevant literature using the search terms of“mitogen-activated protein kinases,osteoarthritis,extracellular signal-regulated MAP kinases,p38 mitogen-activated protein kinases,JNK mitogen-activated protein kinase”in Chinese and English.Relevant literature published from January 2019 to November 2024 was searched,and 108 articles were finally included for summary analysis.RESULTS AND CONCLUSION:(1)Various stimuli inside and outside the cells activate the MAPK signaling pathway,regulate gene transcription and protein synthesis,and promote the release of inflammatory factors,such as tumor necrosis factor-α,interleukin-1β,and interleukin-6.The release of these inflammatory factors aggravates the progression of osteoarthritis.(2)The active ingredients of traditional Chinese medicine,mainly saponins and flavonoids,as well as Chinese herbal formulas and preparations with the main effects of activating blood circulation and removing blood stasis,tonifying the liver and kidney,can play a therapeutic role in osteoarthritis by inhibiting the MAPK signaling pathway,regulating the release of matrix metalloproteinases,balancing the homeostatic state of osteogenesis and osteoblastogenesis,attenuating the synovial inflammation,decreasing the release of inflammatory factors and inflammatory vesicles,decreasing cellular pyroptosis,promoting autophagy,and ameliorating oxidative stress.(3)Although traditional Chinese medicine has become popular in the treatment of osteoarthritis by virtue of its own advantages of multi-components,multi-targets,multi-pathways,and low side effects,the use of MAPK signaling pathway to guide the treatment of individual osteoarthritis is the difficulty of the technology,which needs to be continuously researched and explored.(4)Therefore,further development of relevant herbal inhibitors that can modulate the MAPK signaling pathway may be a potential drug strategy for the treatment of osteoarthritis in the future.
作者
李豪
陶红成
曾平
刘金富
丁强
牛驰程
黄凯
康宏誉
Li Hao;Tao Hongcheng;Zeng Ping;Liu Jinfu;Ding Qiang;Niu Chicheng;Huang Kai;Kang Hongyu(Guangxi University of Chinese Medicine,Nanning 530200,Guangxi Zhuang Autonomous Region,China;The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,Guangxi Zhuang Autonomous Region,China)
出处
《中国组织工程研究》
北大核心
2026年第6期1476-1485,共10页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金项目(82160913),项目负责人:曾平
广西研究生教育创新计划项目(硕士区级,YCSW202446),项目参与人:李豪。
关键词
丝裂原活化蛋白激酶信号通路
骨关节炎
软骨细胞
中药
皂苷类
黄酮类
mitogen-activated protein kinase signaling pathway
osteoarthritis
chondrocyte
Chinese medicine
saponins
flavonoids
作者简介
第一作者:李豪,男,1996年生,四川省广元市人,汉族,广西中医药大学在读硕士,医师,主要从事骨关节退变与缺血性疾病的中医防治研究,https://orcid.org/0009-0001-0972-9821;通讯作者:曾平,博士,博士后,主任医师,广西中医药大学第一附属医院,广西壮族自治区南宁市530023。
