17β‐estradiol aggravates temporomandibular joint inflammation through the NF‐κB pathway in ovariectomized rats

• Published in: Arthritis and rheumatism 2011-07, Vol.63 (7), p.1888-1897
• Main Authors: Kou, Xiao‐Xing, Wu, Yu‐Wei, Ding, Yun, Hao, Ting, Bi, Rui‐Yun, Gan, Ye‐Hua, Ma, Xuchen
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Diseases of the osteoarticular system; Dose-Response Relationship, Drug; Electrophoretic Mobility Shift Assay; Estradiol - analogs & derivatives; Estradiol - metabolism; Estradiol - pharmacology; Female; Fluorescent Antibody Technique; Inflammation - metabolism; Inflammation - pathology; Medical sciences; NF-kappa B - metabolism; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - drug effects; Temporomandibular Joint - drug effects; Temporomandibular Joint - metabolism; Temporomandibular Joint - pathology
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.30334

Objective Women of childbearing age are more likely than men to experience temporomandibular disorders, with pain as the main symptom. Temporomandibular joint (TMJ) inflammation is believed to be a major reason for TMJ pain. Whether sex hormones are involved in the sexual dimorphism of TMJ inflammation and pain remains to be elucidated. The aim of this study was to examine whether estrogen affects TMJ inflammation and pain via the NF‐κB pathway. Methods Female rats were divided into 6 groups: the control group, the sham‐ovariectomized group, and 4 groups of ovariectomized rats treated with 17β‐estradiol at a dosage of 0 μg/day, 20 μg/day, 80 μg/day, and 200 μg/day, respectively, for 10 days and then injected intraarticularly with Freund's complete adjuvant to induce TMJ inflammation. The behavior‐related and histologic effects of 17β‐estradiol were evaluated 24 hours after the induction of TMJ inflammation. NF‐κB activity in the synovial membrane was examined by electrophoretic mobility shift assay. The expression of the NF‐κB target genes tumor necrosis factor α, interleukin‐1β (IL‐1β), IL‐6, cyclooxygenase 2, and inducible nitric oxide synthase in the synovial membrane was examined by real‐time polymerase chain reaction. Results Treatment with estradiol potentiated TMJ inflammation in a dose‐dependent manner and also exacerbated the inflammation‐induced decrease in food intake. Correspondingly, estradiol potentiated the DNA‐binding activity of NF‐κB and the transcription of its target genes in the synovial membrane. Furthermore, the estrogen receptor antagonist ICI 182780 or the NF‐κB inhibitor pyrrolidine dithiocarbamate partially blocked the effects of estradiol on TMJ inflammation and pain and the NF‐κB pathway. Conclusion These results suggest that estradiol aggravates TMJ inflammation through the NF‐κB pathway, leading to the induction of proinflammatory cytokines.