OX40L in endothelial cells promotes temporomandibular joint subchondral bone angiogenesis and osteoclastogenesis in mice

  • Bone Joint Res. 2026 Apr 1;15(4):342-353. doi: 10.1302/2046-3758.154.BJR-2025-0249.R1.
Yifan Zheng  1 ,  Chufeng Liu  2 ,  Zhihao Liao  2 ,  Jiayu Lin  2 ,  Yuxiao Luo  1 ,  Xia Yang  3 ,  Xuepei Cai  4 ,  Zedong Lan  1
Affiliations
  • 1. Shenzhen Stomatological Hospital, Southern Medical University, Shenzhen, China.
  • 2. Department of Orthodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, China.
  • 3. The Sixth People's Hospital of Chengdu, Chengdu, China.
  • 4. Department of Pediatric Dentistry, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, China.
PMID: 41916570 DOI: 10.1302/2046-3758.154.BJR-2025-0249.R1
Abstract

Aims: Subchondral vascular proliferation is a substantial pathological manifestation of temporomandibular joint osteoarthritis (TMJOA), yet its underlying mechanisms remain unclear. This study aimed to investigate the role of OX40-OX40L signalling in mediating subchondral angiogenesis and osteoclastogenesis in early stage TMJOA.

Methods: A unilateral anterior cross-bite (UAC) model was established in mice to induce TMJOA, and the expression of OX40L in subchondral vessels was examined at the early stages of the disease. In vitro, the OX40-OX40L pathway was activated in bone microvascular endothelial cells (BMECs) to assess its effects on cell migration, tube formation, and osteoclast differentiation. An OX40L monoclonal antibody was used during in vivo experiments to block this signalling pathway.

Results: We observed increased expression of OX40L in the subchondral vessels during early TMJOA, accompanied by significant bone destruction. OX40L activation enhanced endothelial cell migration and angiogenesis in vitro, whereas pathway inhibition reversed these effects and reduced osteoclast differentiation. In vivo, OX40L monoclonal antibody effectively alleviated subchondral angiogenesis and osteoclastogenesis.

Conclusion: Endothelial OX40L signalling promotes pathological subchondral angiogenesis and osteoclastogenesis in early TMJOA.

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