• J. Steroid Biochem. Mol. Biol. · Sep 2014

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

    • Xiao-Xing Kou, Xue-Dong Wang, Chen-Shuang Li, Rui-Yun Bi, Zhen Meng, Bei Li, Yan-Heng Zhou, and Ye-Hua Gan.
    • Department of Orthodontics, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China; Center for Craniofacial Stem Cell Research and Regeneration, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China.
    • J. Steroid Biochem. Mol. Biol. 2014 Sep 1;143:444-50.

    AbstractEstrogen 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.Copyright © 2014. Published by Elsevier Ltd.

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