Association of HMGB1 levels in synovial fluid with the severity of temporomandibular joint osteoarthritis

Abstract

BackgroundHMGB1 usually serves as a damage-associated molecular pattern (DAMP) molecule (also known as alarmin) that regulates the inflammatory and immune responses via different receptors or direct uptake. Numerous studies have reported the association between HMGB1 and inflammatory diseases; however, its role in temporomandibular joint (TMJ) osteoarthritis (OA) has not been elucidated. In this retrospective study, we aimed to investigate HMGB1 levels in the synovial fluid (SF) in patients with TMJOA and TMID, their correlation with TMJOA and TMID severity, and the therapeutic effect of sodium hyaluronate (hyaluronic acid, HA) on TMJOA.MethodsSF samples were analyzed for 30 patients with TMJ internal derangement (TMJID) and TMJOA, along with visual analog scale (VAS) scores, radiographic stages, and mandibular functional limitations. The SF levels of HMGB1, IL-1β, IL-18, PGE2, RAGE, TLR4, and iNOS were determined via an enzyme-linked immunosorbent assay. To evaluate the therapeutic effects of HA, pre-treatment and post-treatment clinical symptoms were also compared in patients of the TMJOA group who had received an intra-articular injection of HA.ResultsVAS and Jaw Functional Limitation Scale (JFLS) scores were significantly higher in the TMJOA group than in the TMNID group, as were SF levels of HMGB1, TLR4, IL-1β, IL-18, PGE2, and iNOS. The synovial HMGB1 level was positively correlated with the VAS score (r = 0.5512, p = 0.0016) and mandibular functional limitations (r = 0.4684, p = 0.0054). The cut-off value for the HMGB1 level as a diagnostic biomarker was 986.8 pg/ml. The SF level of HMGB1 yielded an area under the curve value (AUC) of 0.8344 for predicting TMJOA. HA alleviated TMJ disorders by significantly reducing the VAS score and improving the maximum extent of mouth opening in both the TMJID and TMJOA groups (p < 0.05). Moreover, patients in both the TMJID and TMJOA groups exhibited significant improvement in the JFLS score following HA treatment.ConclusionsOur results indicate that HMGB1 is a potential marker for predicting the severity of TMJOA. Intra-articular HA injection exerts a positive therapeutic effect on TMJOA; however, further investigations are warranted to validate its therapeutic effect in the late phase of visco-supplementation treatment.