基于Wnt5a/Ror2信号通路调控的颞下颌关节骨关节炎软骨下骨破坏机制研究

doi:10.13701/j.cnki.kqyxyj.2025.11.007

口腔医学研究 ›› 2025, Vol. 41 ›› Issue (11): 964-969.DOI: 10.13701/j.cnki.kqyxyj.2025.11.007

基于Wnt5a/Ror2信号通路调控的颞下颌关节骨关节炎软骨下骨破坏机制研究

陈磊¹, 卜银忠^1,2*, 任振萍¹, 孙佩佩¹, 匡斌^1*

1.甘肃省兰州市第一人民医院口腔科甘肃兰州 730050;
2.兰州大学第一临床医学院甘肃兰州 730000

收稿日期:2025-04-25 出版日期:2025-11-28 发布日期:2025-11-25
通讯作者: *卜银忠,E-mail:buyinzhong@163.com; 匡斌,E-mail:kuangbin1233@163.com
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。
基金资助:
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)

Mechanism of Subchondral Bone Destruction in TMJ-OA Regulated by Wnt5a/Ror2 Signaling Pathway

CHEN Lei¹, BU Yinzhong^1,2*, REN Zhenping¹, SUN Peipei¹, KUANG Bin^1*

1. Department of Stomatology, First People's Hospital, Lanzhou 730050, China;
2. The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, China

Received:2025-04-25 Online:2025-11-28 Published:2025-11-25

摘要/Abstract

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1 μg 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。

关键词: 颞下颌关节骨关节炎, 软骨下骨, 流体剪切应力

Abstract: 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.

Key words: temporomandibular joint osteoarthritis, subchondral bone, fluid shear stress

陈磊, 卜银忠, 任振萍, 孙佩佩, 匡斌. 基于Wnt5a/Ror2信号通路调控的颞下颌关节骨关节炎软骨下骨破坏机制研究[J]. 口腔医学研究, 2025, 41(11): 964-969.

CHEN Lei, BU Yinzhong, REN Zhenping, SUN Peipei, KUANG Bin. Mechanism of Subchondral Bone Destruction in TMJ-OA Regulated by Wnt5a/Ror2 Signaling Pathway[J]. Journal of Oral Science Research, 2025, 41(11): 964-969.

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基于Wnt5a/Ror2信号通路调控的颞下颌关节骨关节炎软骨下骨破坏机制研究

Mechanism of Subchondral Bone Destruction in TMJ-OA Regulated by Wnt5a/Ror2 Signaling Pathway

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