2. Academic Validation
  3. Mechanical overload induces TMJ disc degeneration via TRPV4 activation

Mechanical overload induces TMJ disc degeneration via TRPV4 activation

  • Oral Dis. 2023 Apr 27. doi: 10.1111/odi.14595.
Sheng-Jie Cui 1,  Fu-Jia Yang 1,  Xue-Dong Wang 1,  Ze-Bin Mao 2,  Yan Gu 1
Affiliations

Affiliations

  • 1 Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing, China.
  • 2 Department of Biochemistry and Biophysics, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Peking University Health Science Center, Beijing, China.
PMID: 37103670 DOI: 10.1111/odi.14595
Abstract

Objective: The temporomandibular joint (TMJ) disc cushions intraarticular stress during mandibular movements. While mechanical overloading is related to cartilage degeneration, the pathogenesis of TMJ disc degeneration is unclear. Here, we determined the regulatory role of mechanoinductive transient receptor potential vanilloid 4 (TRPV4) in mechanical overload-induced TMJ disc degeneration.

Methods: We explored the effect of mechanical overload on the TMJ discs in a rat occlusal interference model in vivo, and by applying sustained compressive force in vitro. TRPV4 inhibition was delivered by small interfering RNA or GSK2193874; TRPV4 activation was delivered by GSK1016790A. The protective effect of TRPV4 inhibition was validated in the rat occlusal interference model.

Results: Occlusal interference induced TMJ disc degeneration with enhanced extracellular matrix degradation in vivo and mechanical overload promoted inflammatory responses in the TMJ disc cells via CA2+ influx with significantly upregulated TRPV4. TRPV4 inhibition reversed mechanical overload-induced inflammatory responses; TRPV4 activation simulated mechanical overload-induced inflammatory responses. Moreover, TRPV4 inhibition alleviated TMJ disc degeneration in the rat occlusal interference model.

Conclusion: Our findings suggest TRPV4 plays a pivotal role in the pathogenesis of mechanical overload-induced TMJ disc degeneration and may be a promising target for the treatment of degenerative changes of the TMJ disc.

Keywords

Ca2+ influx; MMPs; TRPV4; mechanical force; temporomandibular joint disc.

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