Progesterone attenuates temporomandibular joint inflammation through inhibition of NF-\u03baB pathway in ovariectomized rats

Xin-Tong Xue,Xue-Dong Wang,Yan-Heng Zhou,Ye-Hua Gan,Rui-Yun Bi,Xiao-Xing Kou,Chen-Shuang Li,Zhen Meng

doi:10.1038/s41598-017-15285-w

Abstract

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.

Highlights

Temporomandibular disorders (TMDs) are approximately twice as prevalent in women than in men, similar to rheumatoid arthritis[1]
Various stimuli and proinflammatory cytokines lead to the nuclear translocation of NF-κB and subsequently promoting transcription of IL-1β, IL-6, and tumor necrosis factor-α (TNF-α)[18], which appear to be the major proinflammatory cytokines involved in TMJ pathology[19]
We explored whether progesterone could attenuate TMJ inflammation and pain, and whether progesterone could inhibit NF-κB activity and NF-κB-modulated transcription of proinflammatory genes in the synovial membrane of inflamed TMJs in ovariectomized rats

Summary

Introduction

Temporomandibular disorders (TMDs) are approximately twice as prevalent (and more severe) in women than in men, similar to rheumatoid arthritis[1]. Sex hormones are reported to be involved in TMD pain[1,2,3]. We and other groups have reported that estrogen aggravates TMJ inflammation or pain through the induction of proinflammatory cytokines in the synovial membrane[6,7,8,9,10,11]. Whether progesterone attenuates to TMJ inflammation and pain remains to be explored. We reported that estrogen-enhanced activation of NF-κB aggravates to TMJ inflammation, and blocking NF-κB attenuates inflammation and pain of TMJ6. Whether progesterone inhibits activation of NF-κB in inflamed joint remains to be examined. We explored whether progesterone could attenuate TMJ inflammation and pain, and whether progesterone could inhibit NF-κB activity and NF-κB-modulated transcription of proinflammatory genes in the synovial membrane of inflamed TMJs in ovariectomized rats

Methods

Results

Conclusion