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Elevated leptin levels in temporomandibular joint osteoarthritis promote proinflammatory cytokine IL ‐6 expression in synovial fibroblasts
Author(s) -
Xiong Haofei,
Li Wei,
Li Jiajie,
Fang Wei,
Ke Jin,
Li Bo,
Cheng Yong,
Wei Lili
Publication year - 2019
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12819
Subject(s) - proinflammatory cytokine , osteoarthritis , cytokine , medicine , temporomandibular joint , leptin , synovial joint , immunology , inflammation , endocrinology , pathology , articular cartilage , alternative medicine , obesity
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 ‐ SF s). 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 ‐ SF s. Small interfering RNA (si RNA ) was transfected into the TMJ ‐ SF s 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 ‐ SF s. 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 ‐ SF s. Leptin can stimulate the mRNA and protein expression of IL ‐6 in TMJ ‐ SF s by binding with Ob‐Rb. The leptin‐induced production of IL ‐6 by the TMJ ‐ SF s significantly decreased after exposure to si RNA targeting Ob‐Rb. Inhibiting JAK 2/ STAT 3, p38 MAPK or PI 3K/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 ‐ SF s via the activation of the JAK 2/ STAT 3, p38 MAPK or PI 3K/Akt signalling pathways.