Matrix Stiffening‐Induced SLIT3 Activation in Chondrocytes Drives Cartilage Degradation and Angiogenesis in Temporomandibular Joint Osteoarthritis
Year: 2025
Type: article
Abstract: Cartilage degeneration and subchondral angiogenesis are key pathological features of temporomandibular joint osteoarthritis (TMJOA). This study aims to investigate the role and regulatory mechanism of SLIT3, a potent pro-angiogenic factor, in driving these processes. Male C57BL/6 mice underwent either sham surgery or unilateral anterior crossbite (UAC) surgery to induce TMJOA. Bilateral temporomandibular joints were harvested at 3 and 6 weeks post-surgery for radiographic, histological, and molecular analyses. Rat primary condylar chondrocytes were isolated for in vitro studies, including loss-of-function experiments to elucidate the role of chondrocyte-derived SLIT3. Early-stage TMJOA was characterized by progressive cartilage degradation and increased subchondral type H vessel formation, accompanied by increased SLIT3 expression in chondrocytes. We identified a previously unrecognized dual function of SLIT3: it not only promoted endothelial tube formation but also suppressed cartilage matrix synthesis. Mechanistically, SLIT3 secretion in chondrocytes was regulated by the Plexin-B2/YAP pathway in response to extracellular matrix (ECM) stiffening. Our findings reveal a novel mechano-driven pathological axis in TMJOA, wherein ECM stiffening activates the Plexin-B2/YAP/SLIT3 axis in chondrocytes, simultaneously driving both type H angiogenesis and cartilage degradation. This study uncovers a critical link between mechanical stimuli, chondrocyte signaling, and vascular invasion, offering new therapeutic targets for TMJOA intervention.
Source: The FASEB Journal
Authors: Yilin Chen, Wenlin Yuan, Ying Wang, Wei Liu, Jiejun Shi
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G2006032589, G2297545100, G4464906429
OpenAlex ID: W4413258029