title: Estradiol-potentiated cadherin-11 in synovial membrane involves in temporomandibular joint inflammation in rats.
abstract: 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.
authors.affiliation: 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.
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Kou
authors.affiliation: 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.
authors.forename: Xue-Dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Department of Orthodontics, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China.
authors.forename: Chen-Shuang
authors.initials: CS
authors.lastname: Li
authors.affiliation: The 3rd Dental Center, Peking University School and Hospital of Stomatology, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China.
authors.forename: Rui-Yun
authors.initials: RY
authors.lastname: Bi
authors.affiliation: Central Laboratory and Center for Temporomandibular Disorders and Orofacial Pain, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Meng
authors.affiliation: The 3rd Dental Center, Peking University School and Hospital of Stomatology, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China.
authors.forename: Bei
authors.initials: B
authors.lastname: Li
authors.affiliation: 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. Electronic address: yanhengzhou@gmail.com.
authors.forename: Yan-Heng
authors.initials: YH
authors.lastname: Zhou
authors.affiliation: Central Laboratory and Center for Temporomandibular Disorders and Orofacial Pain, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, PR China. Electronic address: kqyehuagan@bjmu.edu.cn.
authors.forename: Ye-Hua
authors.initials: YH
authors.lastname: Gan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000037:antagonists & inhibitors*; D004958:Estradiol / Q000633:toxicity*; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology*; D013704:Temporomandibular Joint / Q000187:drug effects / Q000473:pathology*
chemical_list: D015820:Cadherins; D004967:Estrogens; D016328:NF-kappa B; D012333:RNA, Messenger; C086960:osteoblast cadherin; D004958:Estradiol
keywords: Cadherin-11; Estrogen; Inflammatory pain; Synoviocytes; TMJ