Abstract
Temporomandibular joint osteoarthritis (TMJOA), a prevalent subtype of temporomandibular disorders, is characterized by progressive cartilage degradation and subchondral bone destruction. Despite advancements in understanding TMJOA pathogenesis, the molecular mechanisms underlying its progression remain unclear. In this study, elevated Slit guidance ligand 2 (SLIT2) expression was observed in TMJ tissues of unilateral anterior crossbite–induced TMJOA mice and synovial fluid from patients with TMJOA, correlating with disease severity. Furthermore, SLIT2 overexpression in transgenic mice intensified TMJOA progression, whereas heterozygous deletion of roundabout guidance receptor 1/2 (ROBO1/2) alleviated cartilage and bone damage. Mechanistically, SLIT2 promoted ROBO1-LRP6 complex formation, facilitating LRP6 phosphorylation and β-catenin nuclear translocation. This cascade upregulated matrix-degrading enzymes while downregulating cartilage structural proteins, exacerbating cartilage destruction and subchondral bone loss. These findings suggest that the SLIT2/ROBO1/LRP6 axis may represent a potential therapeutic target for TMJOA and provide mechanistic insights into disease progression.
Authors
Guan Luo, Baoyi Chen, Wenjun Chen, Huiyi Lin, Weiqi Guo, Qingbin Zhang, Jiang Li, Lijing Wang, Janak Lal Pathak, Yuhui Yang, Weijun Zhang, Xiaoyu Zhang, Beining Zheng, Ziyi Wang, Shiting Wei, Jiaxin He, Wei-Jie Zhou, Chang Liu
Graphical abstract
