Steffens João Paulo, Valenga Henrique Meister, Santana Luis Carlos Leal, Albaricci Maria Carolina da Costa, Kantarci Alpdogan, Spolidorio Luis Carlos
Department of Stomatology, Universidade Federal do Paraná - UFPR, Curitiba, PR, Brazil.
Department of Physiology and Pathology, School of Dentistry at Araraquara, Universidade Estadual Paulista - UNESP, Araraquara, SP, Brazil.
J Periodontol. 2020 Apr;91(4):545-553. doi: 10.1002/JPER.19-0099. Epub 2019 Aug 25.
Sex hormone therapy has strict recommendations in the treatment of postmenopausal symptoms, in which testosterone (TES) replacement may play a potential role. However, it remains unclear whether TES affects the course of chronic inflammation and alveolar bone loss in females. Herein, we investigated the role of androgen receptor and TES on the inflammatory response and alveolar bone resorption associated with ligature-induced periodontal disease in female rats.
Fifty female Holtzman rats were divided in five groups (n = 10/group): androgen receptor antagonist (flutamide); estrogen receptor antagonist (fulvestrant); TES supplementation; aromatase inhibitor (anastrozole); and TES plus anastrozole. Periodontitis was induced by ligatures around the lower first molars for 2 weeks. Twenty animals (n = 10/group) were used as untreated ligated or non-ligated controls. Bone loss and the number of osteoclasts were measured through radiographic and immunohistochemical analysis, respectively. Inflammatory cytokines, chemokines and bone markers were measured by multiplex immunoassay and ELISA in serum samples and periodontal tissues.
The blockage of androgen receptor significantly increased radiographic bone loss and tissue levels of IL-1α (P <0.05), IL-1β (P <0.001) and IL-10 (P <0.01) compared with the periodontitis group. Testosterone supplementation significantly increased EGF levels in tissue samples, whereas when combined with aromatase inhibitor anastrozole significantly increased both EGF and VEGF (P <0.05). None of the treatment conditions significantly impacted the number of osteoclasts compared with the periodontitis group.
Androgen receptor activation is an important factor in the regulation of several inflammatory markers, and its blockage significantly increases bone loss.
性激素疗法在绝经后症状治疗中有严格的推荐标准，其中睾酮（TES）替代可能发挥潜在作用。然而，TES是否影响女性慢性炎症进程和牙槽骨丧失仍不清楚。在此，我们研究了雄激素受体和TES在雌性大鼠结扎诱导的牙周病相关炎症反应和牙槽骨吸收中的作用。
将50只雌性霍尔兹曼大鼠分为五组（每组n = 10）：雄激素受体拮抗剂（氟他胺）组；雌激素受体拮抗剂（氟维司群）组；TES补充组；芳香化酶抑制剂（阿那曲唑）组；TES加阿那曲唑组。通过在下颌第一磨牙周围结扎2周诱导牙周炎。20只动物（每组n = 10）用作未治疗的结扎或未结扎对照。分别通过影像学和免疫组织化学分析测量骨丧失和破骨细胞数量。通过多重免疫测定和酶联免疫吸附测定法测量血清样本和牙周组织中的炎性细胞因子、趋化因子和骨标志物。
与牙周炎组相比，雄激素受体阻断显著增加了影像学骨丧失以及IL-1α（P <0.05）、IL-1β（P <0.001）和IL-10（P <0.01）的组织水平。补充TES显著增加了组织样本中的表皮生长因子（EGF）水平，而与芳香化酶抑制剂阿那曲唑联合使用时显著增加了EGF和血管内皮生长因子（VEGF）两者水平（P <0.05）。与牙周炎组相比，所有治疗条件均未对破骨细胞数量产生显著影响。
雄激素受体激活是调节多种炎症标志物的重要因素，其阻断显著增加骨丧失。
