Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
Center for Craniofacial Stem Cell Research and Regeneration, Peking University School and Hospital of Stomatology, Beijing, China.
Sci Rep. 2017 Nov 10;7(1):15334. doi: 10.1038/s41598-017-15285-w.
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.
性激素可能与女性为主的颞下颌关节紊乱病（TMD）炎症性疼痛的症状有关。孕妇的 TMD 症状比非孕妇少。孕激素（P4）作为调节多种生物学功能的主要性激素之一，是否参与 TMD 的症状仍有待探讨。弗氏完全佐剂用于诱导关节炎症。我们评估了 P4 对行为相关和组织学的影响，以及 TNF-α、IL-1β 和 IL-6 在滑膜中的表达。用 TNF-α或 IL-1β联合 P4 处理原发性 TMJ 滑膜细胞。进一步应用孕激素受体拮抗剂 RU-486。我们发现 P4 替代治疗以剂量依赖的方式减轻了去卵巢大鼠 TMJ 的炎症和痛觉反应。相应地，P4 以剂量依赖的方式减弱了 TMJ 滑膜中 NF-κB 的 DNA 结合活性及其靶基因的转录。此外，P4 处理显示促炎细胞因子的 mRNA 表达减少，并部分逆转了 TNF-α和 IL-1β诱导的促炎细胞因子的转录。此外，孕激素受体拮抗剂 RU-486 部分逆转了 P4 对 NF-κB 通路的作用。总之，孕激素通过抑制 NF-κB 通路改善了 TMJ 炎症。
