Toll-Like Receptor 4 (TLR4) Stimulates Synovial Injury of Temporomandibular Joint in Rats Through the Activation of p38 Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway.

Abstract

BackgroundSynovitis is an important disease that cause intractable pain in temporomandibular joint (TMJ), and the inflammation process played a crucial role in the initiation and development of temporomandibular joint disorder. A series of investigations suggested that the increasing expression of interleukin-(IL) 1β secreted by synovial lining cells plays an important role in synovial inflammation and cartilage destruction in TMJ. In this present study, we investigated the signaling pathways which regulate the expression of IL-1β.Material/MethodsThe occlusal interference animal model was created to induce synovial injury. Forty-eight rats were divided into 4 groups: 1) control group, 2) occlusal interference group, 3) TAK-242 (a specific inhibitor targeting the Toll-like receptor (TLR)-4) group, and 4) SB203580 (a specific inhibitor targeting the p38) group. The inflammation changes were observed, and the expression of p38 and IL-1β in the synovial membranes were assayed.ResultsThe results showed that downstream p38 MAPK (mitogen-activated protein kinase) signaling was triggered following the activation of TLR4. Moreover, the injection of SB203580 could inhibit the inflammatory reactions and the increased expression of IL-1β at both mRNA and protein levels.ConclusionsThe results prompted us that TLR4 may stimulates synovial inflammatory reactions and increased expression of IL-1β in rats through the activation of p38 MAPK signaling pathway, p38 was an important mediator in the mechanisms of the initiation and development of synovial injury by regulating the expression of IL-1β in synovial membranes.