摘要
目的:探讨瞬时受体电位离子通道蛋白7(TRPM7)/钙调素依赖性蛋白激酶Ⅱ(CaMKⅡ)/SMAD1信号通路在膝骨关节炎(KOA)软骨组织损伤中的作用,为治疗KOA提供新参考。方法:收集需要手术的KOA患者(KOA组)和创伤无KOA的患者(非KOA组)各15例为研究对象,制备关节软骨组织。酶联免疫吸附法(ELISA)检测关节软骨组织炎症因子一氧化氮合酶(iNOS)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平。流式细胞术测定关节软骨组织活性氧(ROS)和Ca^(2+)水平。实时荧光定量PCR(RT-qPCR)检测关节软骨组织TRPM7基因表达。Western blot检测关节软骨组织TRPM7/CaMKⅡ/SMAD1信号通路相关蛋白表达。结果:与非KOA组比较,KOA组关节软骨组织iNOS、TNF-α、IL-6、ROS、Ca^(2+)水平升高,TRPM7基因及TRPM7、p-CaMKⅡ、p-SMAD1蛋白呈高表达(均P<0.05)。结论:KOA患者软骨组织处于炎症状态和高氧化应激状态。TRPM7激活触发Ca^(2+)内流,激活下游靶蛋白CaMKⅡ和SMAD1,进而调节软骨细胞活性。TRPM7/CaMKⅡ/SMAD1信号通路可能是KOA的发病机制之一。
Objective:To investigate the role of transient receptor potential melastatin 7(TRPM7)/calmodulin-dependent protein kinaseⅡ(CaMKⅡ)/SMAD1 signaling pathway in cartilage tissue injury in knee osteoarthritis(KOA),and to provide a new reference for the treatment of KOA.Methods:Fifteen patients with KOA who needed surgery(KOA group)and 15 trauma patients without KOA(non-KOA group)were collected as research objects,and articular cartilage tissue was prepared.In articular cartilage tissue,ELISA was used to detect the levels of inflammatory factors iNOS,TNF-αand IL-6,Flow cytometry was used to measure ROS and Ca^(2+)levels,RT-qPCR was used to detect the expression of TRPM7 gene,and Western blot was used to detect the expression of TRPM7/CaMKⅡ/SMAD1 signaling pathway related proteins.Results:Compared with the non-KOA group,the levels of iNOS,TNF-α,IL-6,ROS and Ca^(2+)in articular cartilage tissue were increased,and the expressions of TRPM7 gene and TRPM7,p-CaMKⅡand p-SMAD1 proteins were increased in the KOA group(all P<0.05).Conclusion:The cartilage tissue of KOA patients is in a state of inflammation and high oxidative stress.TRPM7 activation triggers Ca^(2+)influx and activates the downstream target proteins CaMKⅡand SMAD1,thereby regulating chondrocyte activity.TRPM7/CaMKⅡ/SMAD1 signaling pathway may be one of the pathogenesis of KOA.
作者
向文远
邓迎杰
梁治权
张文豪
方锐
XIANG Wenyuan;DENG Yingjie;LIANG Zhiquan;ZHANG Wenhao;FANG Rui(Department of Joint Surgery,the Fourth Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China)
出处
《陕西医学杂志》
2025年第12期1596-1600,1634,共6页
Shaanxi Medical Journal
基金
国家自然科学基金资助项目(82405423)。
关键词
膝骨关节炎
软骨组织
瞬时受体电位离子通道蛋白7
钙调素依赖性蛋白激酶Ⅱ
炎症因子
氧化应激
钙离子
信号通路
Knee osteoarthritis
Cartilage tissue
Transient receptor potential melastatin 7
Calmodulin-dependent protein kinaseⅡ
Inflammatory factors
Oxidative stress
Calcium ion
Signaling pathway
