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Peer-reviewedCC BYInternational journal of molecular sciences

Bone Morphogenetic Protein-2 and Cabozantinib for Temporomandibular Joint Cartilage Repair: Murine and Porcine Injury Models

  • Max L. Silverstein1
  • Sophia Hou1
  • Chunxi Ge2
  • Tanya C. Garcia3
  • Charles K. F. Chan1
  • Karl C. Bruckman1
  • Eri Takematsu1,2
  1. 1Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, 770 Welch Rd. Ste 400, Stanford, CA 94305, USA
  2. 2Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109, USA
  3. 3Veterinary Institute for Regenerative Cures, School of Veterinary Medicine, University of California, Davis, 1 Shields Ave., Davis, CA 95616, USA
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Abstract

Temporomandibular joint osteoarthritis (TMJ OA) is characterized by progressive degeneration of the fibrocartilaginous articular surface. We previously demonstrated that combined bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) inhibition promotes endogenous hyaline cartilage regeneration in appendicular joints. Whether this regenerative strategy can be extended to the specialized fibrocartilage of the TMJ remains unknown. In this study, we evaluated the regenerative potential of BMP-2 combined with cabozantinib, an FDA-approved multikinase inhibitor with activity against VEGF receptors, using complementary murine and porcine TMJ cartilage injury models. In mice, needle-induced abrasion of the mandibular condyle resulted in loss of the fibrocartilaginous articular surface and extracellular matrix; treatment with BMP-2 and cabozantinib was associated with improved cartilage architecture and increased fibrocartilage thickness. To examine translational feasibility, we developed a surgically accessible porcine TMJ cartilage defect model and demonstrated the technical feasibility of local BMP-2 and cabozantinib delivery with formation of repair tissue within the defect. Collectively, these findings provide preliminary evidence supporting further investigation of combined BMP-2 and cabozantinib for TMJ cartilage repair.

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Cite

BibTeXRIS
BibTeX
@article{silverstein2026bone,
  title = {{Bone Morphogenetic Protein-2 and Cabozantinib for Temporomandibular Joint Cartilage Repair: Murine and Porcine Injury Models}},
  author = {Max L. Silverstein and Sophia Hou and Chunxi Ge and Tanya C. Garcia and Charles K. F. Chan and Karl C. Bruckman and Eri Takematsu},
  journal = {International journal of molecular sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27198937},
  url = {https://europepmc.org/article/PMC/PMC13665104},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Bone Morphogenetic Protein-2 and Cabozantinib for Temporomandibular Joint Cartilage Repair: Murine and Porcine Injury Models
AU  - Max L. Silverstein
AU  - Sophia Hou
AU  - Chunxi Ge
AU  - Tanya C. Garcia
AU  - Charles K. F. Chan
AU  - Karl C. Bruckman
AU  - Eri Takematsu
PY  - 2026
DA  - 2026/10/01
JO  - International journal of molecular sciences
DO  - 10.3390/ijms27198937
UR  - https://europepmc.org/article/PMC/PMC13665104
AB  - Temporomandibular joint osteoarthritis (TMJ OA) is characterized by progressive degeneration of the fibrocartilaginous articular surface. We previously demonstrated that combined bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) inhibition promotes endogenous hyaline cartilage regeneration in appendicular joints. Whether this regenerative strategy can be extended to the specialized fibrocartilage of the TMJ remains unknown. In this study, we evaluated the regenerative potential of BMP-2 combined with cabozantinib, an FDA-approved multikinase inhibitor with activity against VEGF receptors, using complementary murine and porcine TMJ cartilage injury models. In mice, needle-induced abrasion of the mandibular condyle resulted in loss of the fibrocartilaginous articular surface and extracellular matrix; treatment with BMP-2 and cabozantinib was associated with improved cartilage architecture and increased fibrocartilage thickness. To examine translational feasibility, we developed a surgically accessible porcine TMJ cartilage defect model and demonstrated the technical feasibility of local BMP-2 and cabozantinib delivery with formation of repair tissue within the defect. Collectively, these findings provide preliminary evidence supporting further investigation of combined BMP-2 and cabozantinib for TMJ cartilage repair.
SN  - 1422-0067
ER  -