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

doi:10.13701/j.cnki.kqyxyj.2025.11.007

Abstract

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

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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