Elevated leptin levels in temporomandibular joint osteoarthritis promote pro‐inflammatory cytokine IL‐6 expression in synovial fibroblasts

Abstract

Background

Leptin, through binding to its special receptor (Ob‐Rb), has potent effects on immunity and inflammation. This study measured the levels of leptin in the synovial fluid of patients with temporomandibular joint osteoarthritis (TMJ‐OA) and healthy controls, determined the expression of Ob‐Rb and explored the effects and signalling pathways involved in leptin‐induced proinflammatory cytokine interleukin (IL)‐6 production in TMJ synovial fibroblasts (TMJ‐SFs).

Methods

Synovial fluid samples were obtained from 16 patients with TMJ‐OA and seven healthy controls. Leptin levels were measured in synovial fluid using enzyme‐linked immunosorbent assay (ELISA). Ob‐Rb expression was determined by quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot in cultured TMJ‐SFs. Small interfering RNA (siRNA) was transfected into the TMJ‐SFs to down‐regulate the expression of Ob‐Rb. qRT‐PCR and ELISA were used to determine the levels of proinflammatory cytokine IL‐6 in leptin‐stimulated TMJ‐SFs. The involved signalling pathways that mediate the leptin‐stimulated production of IL‐6 were investigated using specific signalling inhibitor analyses.

Results

Compared with healthy controls, patients with TMJ‐OA had significantly higher concentrations of leptin in their synovial fluid. The expression levels of Ob‐Rb mRNA and proteins were detected in the TMJ‐SFs. Leptin can stimulate the mRNA and protein expression of IL‐6 in TMJ‐SFs by binding with Ob‐Rb. The leptin‐induced production of IL‐6 by the TMJ‐SFs significantly decreased after exposure to siRNA targeting Ob‐Rb. Inhibiting JAK2/STAT3, p38 MAPK or PI3K/Akt substantially decreased leptin‐induced IL‐6 production.

Conclusion

Leptin may up‐regulate IL‐6 production in vitro by binding with Ob‐Rb in TMJ‐SFs via the activation of the JAK2/STAT3, p38 MAPK or PI3K/Akt signalling pathways.

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