Estradiol-potentiated cadherin-11 in synovial membrane involves in temporomandibular joint inflammation in rats

• Published in: The Journal of steroid biochemistry and molecular biology 2014-09, Vol.143, p.444-450
• Main Authors: Kou, Xiao-Xing, Wang, Xue-Dong, Li, Chen-Shuang, Bi, Rui-Yun, Meng, Zhen, Li, Bei, Zhou, Yan-Heng, Gan, Ye-Hua
• Format: Article
• Language: English
• Subjects: Animals; Blotting, Western; Cadherins - antagonists & inhibitors; Estradiol - toxicity; Estrogens - toxicity; Female; Flow Cytometry; Inflammation - chemically induced; Inflammation - prevention & control; NF-kappa B - genetics; NF-kappa B - metabolism; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Synovial Membrane - drug effects; Synovial Membrane - pathology; Temporomandibular Joint - drug effects; Temporomandibular Joint - pathology
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2014.07.002

Estrogen is involved in inflammation/pain of temporomandibular joint (TMJ), but the underlying mechanisms are largely unknown. Cadherin-11 plays an essential role in synovial inflammation. This study examined whether estrogen could potentiate cadherin-11 in synoviocytes and contribute to TMJ inflammatory pain. Female rats were ovariectomized, treated with increasing doses of 17β-estradiol for 10 days, and injected intra-articularly with complete Freund's adjuvant to induce TMJ inflammation. The expression of cadherin-11 in synovial membrane was evaluated. TMJ pain was blocked with intra-articular injection of anti-cadherin-11 antibody and evaluated by head withdrawal threshold. Primary TMJ synoviocytes were treated with estradiol and tumor necrosis factor (TNF)-α or blocked with anti-cadherin-11 antibody to assess the expression of cadherin-11, interleukin (IL)-6, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). We observed that estradiol potentiated the inflammation-induced expression of cadherin-11 in the synoviocytes of synovial membrane from inflamed TMJ. Estradiol induced cadherin-11 expression in a dose- and time-dependent manner in primary synoviocytes and further potentiated the induction of cadherin-11 by TNF-α in synoviocytes. Furthermore, an estrogen receptor antagonist or a NF-κB inhibitor partially blocked the effects of estradiol on cadherin-11 induction in the synovial membrane. Blocking cadherin-11 partially reversed the TMJ inflammatory pain and estradiol-potentiated proliferation of synovial lining cells accompanied with iNOS expression. In addition, blocking cadherin-11 reversed TNF-α-induced and estradiol-potentiated transcription of IL-6, COX-2, and iNOS in primary synoviocytes. These results suggest that estrogen aggravated TMJ inflammatory pain partially through cadherin-11-mediated release of proinflammatory cytokines and enzymes in the synoviocytes.