Association of glutamine metabolites in synovial fluid with the severity of temporomandibular joint osteoarthritis

Abstract

Background: The aim of this study was to compare the levels of glutamine and its metabolites, including glutamate, glutaminase (GLS), and α-ketoglutarate (α-KG), in the synovial fluid (SF) of temporomandibular joint osteoarthritis (TMJ-OA) and temporomandibular joint internal derangement (TMJ-ID) patients. Correlations between these factors and TMJ-OA severity were assessed, and changes in these factors before and after hyaluronic acid (HA) treatment were analysed.

Methods: SF samples from 30 patients with unilateral TMJ-ID and unilateral TMJ-OA were analysed, along with visual analogue scale (VAS) scores, maximum mouth opening (MMO), and radiographic stages. The SF levels of glutamine, glutamate, GLS, and α-KG were determined via an enzyme-linked immunosorbent assay. Spearman correlation was used to assess the relationships between SF components and VAS scores, MMO, and imaging severity. ROC curve analysis was used to evaluate each factor's ability to predict TMJ-OA and TMJ-ID. To assess the efficacy of HA treatment for TMJ-OA, VAS scores, MMO, and these factors in SF were also compared in patients in the TMJ-OA group who had received an intra-articular injection of HA.

Results: SF levels of glutamate and GLS were significantly greater in the TMJ-OA group than in the TMJ-ID group, whereas glutamine and α-KG levels were lower. The glutamine SF level was negatively correlated with the radiographic stage (r = -0.5439, P = 0.0019) and MMO (r = -0.4784, P = 0.0075), whereas glutamate was positively correlated with VAS score (r = 0.6681, P = 0.0001). Glutamate shows promise as a TMJ-OA diagnostic marker. The-cut-off value of glutamate in SF was 0.12 µM/ml, with an area under the curve value of 0.9394 for predicting TMJ-OA. After HA injection for TMJ-OA, the MMO improved, and the VAS score and glutamate level decreased significantly (all P < 0.05).

Conclusions: Our results indicate alterations in glutamine metabolism in patients with TMJ-OA. Glutamate has potential as a diagnostic marker for TMJ-OA. The concentration of glutamine was associated with the radiographic stage and MMO of TMJ-OA patients, whereas the glutamate level was correlated with VAS pain intensity. The glutamine metabolic pathway may be critical in the pathogenesis of TMJ-OA.