title: Estradiol promotes M1-like macrophage activation through cadherin-11 to aggravate temporomandibular joint inflammation in rats.
abstract: Macrophages play a major role in joint inflammation. Estrogen is involved in rheumatoid arthritis and temporomandibular disorders. However, the underlying mechanism is still unclear. This study was done to verify and test how estrogen affects M1/M2-like macrophage polarization and then contributes to joint inflammation. Female rats were ovariectomized and treated with increasing doses of 17β-estradiol for 10 d and then intra-articularly injected with CFA to induce temporomandibular joint (TMJ) inflammation. The polarization of macrophages and expression of cadherin-11 was evaluated at 24 h after the induction of TMJ inflammation and after blocking cadherin-11 or estrogen receptors. NR8383 macrophages were treated with estradiol and TNF-α, with or without blocking cadherin-11 or estrogen receptors, to evaluate the expression of the M1/M2-like macrophage-associated genes. We found that estradiol increased the infiltration of macrophages with a proinflammatory M1-like predominant profile in the synovium of inflamed TMJ. In addition, estradiol dose-dependently upregulated the expressions of the M1-associated proinflammatory factor inducible NO synthase (iNOS) but repressed the expressions of the M2-associated genes IL-10 and arginase in NR8383 macrophages. Furthermore, estradiol mainly promoted cadherin-11 expression in M1-like macrophages of inflamed TMJ. By contrast, blockage of cadherin-11 concurrently reversed estradiol-potentiated M1-like macrophage activation and TMJ inflammation, as well as reversed TNF-α-induced induction of inducible NO synthase and NO in NR8383 macrophages. The blocking of estrogen receptors reversed estradiol-potentiated M1-like macrophage activation and cadherin-11 expression. These results suggested that estradiol could promote M1-like macrophage activation through cadherin-11 to aggravate the acute inflammation of TMJs.
authors: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China; and Central Laboratory and Center for Temporomandibular Disorders and Orofacial Pain, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China.
authors: Xiao-Xing
authors: XX
authors: Kou
authors: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China; and.
authors: Chen-Shuang
authors: CS
authors: Li
authors: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China; and.
authors: Dan-Qing
authors: DQ
authors: He
authors: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China; and.
authors: Xue-Dong
authors: XD
authors: Wang
authors: Central Laboratory and Center for Temporomandibular Disorders and Orofacial Pain, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China.
authors: Ting
authors: T
authors: Hao
authors: Central Laboratory and Center for Temporomandibular Disorders and Orofacial Pain, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China.
authors: Zhen
authors: Z
authors: Meng
authors: Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China; and yanhengzhou@gmail.com kqyehuagan@bjmu.edu.cn.
authors: Yan-Heng
authors: YH
authors: Zhou
authors: Central Laboratory and Center for Temporomandibular Disorders and Orofacial Pain, Peking University School and Hospital of Stomatology, Beijing 100081, People's Republic of China yanhengzhou@gmail.com kqyehuagan@bjmu.edu.cn.
authors: Ye-Hua
authors: YH
authors: Gan
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001168:Arthritis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000276:immunology* / Q000494:pharmacology; D065171:Estrogen Receptor Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000276:immunology / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018613:Microscopy, Confocal; D009569:Nitric Oxide / Q000276:immunology / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010052:Ovariectomy; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013704:Temporomandibular Joint / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
chemical_list: D015820:Cadherins; D065171:Estrogen Receptor Antagonists; D004967:Estrogens; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C086960:osteoblast cadherin; D000077267:Fulvestrant; D009569:Nitric Oxide; D004958:Estradiol; D052247:Nitric Oxide Synthase Type II; D001119:Arginase