摘要
目的:探讨异常机械负荷下颞下颌关节骨关节炎(temporomandibular joint osteoarthritis, TMJ-OA)软骨下骨退变过程中受体酪氨酸激酶样孤儿受体2(receptor tyrosine kinase-like orphan receptor 2, Ror2)与Wnt5a的相互作用。方法:采用流体剪切应力(fluid shear stress, FSS)刺激预处理抑制剂后的骨髓间充质干细胞(bone marrow mesenchymal stem cells, BMSCs),检测Wnt5a和Ror2的表达变化;通过关节腔注射不同剂量可溶性Ror2融合蛋白(soluble Ror2, sRor2)干预TMJ-OA大鼠,结合micro-CT和组织学染色评估软骨下骨退变程度。结果:FSS可以有效上调Wnt5a和Ror2的表达,且在20 dynes/cm2的流体剪应力施加60 min时达到峰值。其中Wnt5a通过信号转导与转录激活因子3(signal transducer and activators of transcription 3,STAT3)信号通路调控,Ror2则依赖核因子κB(nuclear factor-κB,NF-κB)和Notch信号通路激活。每周1μg sRor2关节腔注射显著缓解TMJ-OA软骨下骨丢失。结论:FSS通过多信号通路协同调控Wnt5a/Ror2表达,靶向抑制该通路可有效延缓TMJ-OA软骨下骨退变,为TMJ-OA治疗提供新靶点。
Objective:To investigate the interaction between receptor tyrosine kinase-Like orphan receptor 2(Ror2)and Wnt5a in subchondral bone degeneration during temporomandibular joint osteoarthritis(TMJ-OA)under abnormal mechanical loading.Methods:Bone marrow mesenchymal stem cells(BMSCs)pretreated with inhibitors were stimulated with fluid shear stress(FSS)to detect changes in Wnt5a and Ror2 expression.TMJ-OA model rats were intra-articularly injected with different doses of soluble Ror2(sRor2),and the degree of subchondral bone degeneration was evaluated using micro-CT and histological staining.Results:FSS significantly upregulated the expression of Wnt5a and Ror2,reaching peak levels at 20 dynes/cm2 for 60 minutes.Wnt5a expression was regulated through the signal transducer and activators of transcription 3(STAT3)signaling pathway,while Ror2 activation was depended on the nuclear factor-κB(NF-κB) and Notch signaling pathways.Weekly intra-articular injection of 1 μg sRor2 markedly alleviated subchondral bone loss in TMJ-OA.FSS coordinately regulates Wnt5a/Ror2 expression through multiple signaling pathways.Conclusion:Targeted inhibition of this pathway effectively delays subchondral bone degeneration in TMJ-OA,providing a novel therapeutic target for TMJ-OA treatment.
作者
陈磊
卜银忠
任振萍
孙佩佩
匡斌
CHEN Lei;BU Yinzhong;REN Zhenping;SUN Peipei;KUANG Bin(Department of Stomatology,First People's Hospital,Lanzhou 730050,China;The First School of Clinical Medicine,Lanzhou University,Lanzhou 730000,China)
出处
《口腔医学研究》
2025年第11期964-969,共6页
Journal of Oral Science Research
基金
兰州市人才创新创业项目(编号:2019-RC-68)
兰州市科技发展计划项目(编号:2024-9-186)。
关键词
颞下颌关节骨关节炎
软骨下骨
流体剪切应力
temporomandibular joint osteoarthritis
subchondral bone
fluid shear stress
作者简介
陈磊(1976~),男,兰州人,本科,副主任医师,从事颞下颌骨关节研究工作;通信作者:卜银忠,E-mail:buyinzhong@163.com;通信作者:匡斌,E-mail:kuangbin1233@163.com。
