1. Academic Validation
  2. TLR4 contributes to the damage of cartilage and subchondral bone in discectomy-induced TMJOA mice

TLR4 contributes to the damage of cartilage and subchondral bone in discectomy-induced TMJOA mice

  • J Cell Mol Med. 2020 Oct;24(19):11489-11499. doi: 10.1111/jcmm.15763.
Xin Liu 1 Heng-Xing Cai 1 Pin-Yin Cao 2 Yaping Feng 1 Heng-Hua Jiang 1 Li Liu 1 Jin Ke 1 Xing Long 1 3
Affiliations

Affiliations

  • 1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
  • 2 State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases &, Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 3 Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Abstract

The abundance of inflammatory mediators in injured joint indicates innate immune reactions activated during temporomandibular joint osteoarthritis (TMJOA) progression. Toll-like Receptor 4 (TLR4) can mediate innate immune reaction. Herein, we aimed to investigate the expression profile and effect of TLR4 in the cartilage and subchondral bone of the discectomy-induced TMJOA mice. The expression of TLR4 and NFκB p65 in the synovium of TMJOA patients was measured by immunohistochemistry, Western blotting and RT-PCR. H&E and Masson staining were utilized to assess the damage of cartilage and subchondral bone of the discectomy-induced TMJOA mice. A TLR4 Inhibitor, TAK-242, was used to assess the effect of TLR4 in the cartilage and subchondral bone of the discectomy-induced TMJOA mice by Safranin O, micro-CT, immunofluorescence and immunohistochemistry. Western blotting was used to quantify the expression and effect of TLR4 in IL-1β-induced chondrocytes. The expression of TLR4 and NFκB p65 was elevated in the synovium of TMJOA patients, compared with the normal synovium. TLR4 elevated in the damaged cartilage and subchondral bone of discectomy-induced TMJOA mice, and the rate of TLR4 expressing chondrocytes positively correlated with OA score. Intraperitoneal injections of TAK-242 ameliorate the extent of TMJOA. Furthermore, TLR4 promotes the expression of MyD88/NFκB, pro-inflammatory and catabolic mediators in cartilage of discectomy-induced TMJOA. Besides, TLR4 participates in the production of MyD88/NFκB, pro-inflammatory and catabolic mediators in IL-1β-induced chondrocytes. TLR4 contributes to the damage of cartilage and subchondral bone in discectomy-induced TMJOA mice through activation of MyD88/NFκB and release of pro-inflammatory and catabolic mediators.

Keywords

TLR4; cartilage; discectomy; osteoarthritis; subchondral bone; temporomandibular joint.

Figures
Products