Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version


Publication Source

Scientific Reports





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Article number 15334




Sex hormones may contribute to the symptomatology of female-predominant temporomandibular disorders (TMDs) inflammatory pain. Pregnant women show less symptoms of TMDs than that of non-pregnant women. Whether progesterone (P4), one of the dominant sex hormones that regulates multiple biological functions, is involved in symptoms of TMDs remains to be explored. Freund's complete adjuvant were used to induce joint inflammation. We evaluated the behavior-related and histologic effects of P4 and the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the synovial membrane. Primary TMJ synoviocytes were treated with TNF-α or IL-1β with the combination of P4. Progesterone receptor antagonist RU-486 were further applied. We found that P4 replacement attenuated TMJ inflammation and the nociceptive responses in a dose-dependent manner in the ovariectomized rats. Correspondingly, P4 diminished the DNA-binding activity of NF-κB and the transcription of its target genes in a dose-dependent manner in the synovial membrane of TMJ. Furthermore, P4 treatment showed decreased mRNA expression of proinflammatory cytokines, and partially reversed TNF-α and IL-1β induced transcription of proinflammatory cytokines in the primary synoviocytes. Moreover, progesterone receptor antagonist RU-486 partially reversed the effects of P4 on NF-κB pathway. In conclusion, progesterone ameliorated TMJ inflammation through inhibition of NF-κB pathway. © 2017 The Author(s).


At the time of publication, author Xiao-Xing Kou was affiliated with the Peking University School and Hospital of Stomatology. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.

At the time of publication, author Chenshuang Li was affiliated with the School of Dentistry, University of California and the Peking University, School and Hospital of Stomatology. Currently, (s)he is a faculty member at the School of Dental Medicine at the University of Pennsylvania.


Animals, Cytokines, Female, Humans, Mifepristone, NF-kappa B, Pregnancy, Pregnancy Complications, Progesterone, Rats, Rats, Sprague-Dawley, Signal Transduction, Synovial Membrane, Temporomandibular Joint, Temporomandibular Joint Disorders, cytokine, immunoglobulin enhancer binding protein, mifepristone, progesterone, animal, antagonists and inhibitors, drug effect, female, human, metabolism, pathology, pregnancy, pregnancy complication, rat, signal transduction, Sprague Dawley rat, synovium, temporomandibular joint, temporomandibular joint disorder



Date Posted: 10 February 2023

This document has been peer reviewed.