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Suppression of alveolar bone resorption by salubrinal in a mouse model of periodontal disease
Life Sciences ( IF 5.2 ) Pub Date : 2021-09-08 , DOI: 10.1016/j.lfs.2021.119938
Fumika Kimura 1 , Ken Miyazawa 1 , Kazunori Hamamura 2 , Masako Tabuchi 1 , Takuma Sato 1 , Yuichiro Asano 1 , Shunsuke Kako 3 , Yuki Aoki 1 , Yoshihiko Sugita 4 , Hatsuhiko Maeda 4 , Akifumi Togari 2 , Shigemi Goto 1
Affiliation  

The relationship between stress to endoplasmic reticulum (ER) and periodontitis has been known, and ER stress induced by results in the loss of alveolar bone. Salubrinal is a small synthetic compound and attenuates ER stress through inhibition of de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). In this study, we examined whether salubrinal attenuates periodontitis in a mouse model of experimental periodontal disease. We evaluated loss of alveolar bone and attachment levels in periodontium using micro-computed tomography (μCT) and hematoxylin-eosin (HE) staining, respectively. Furthermore, we measured osteoclast numbers using tartrate-resistant acid phosphatase (TRAP) staining and osteoblast numbers using HE staining for bone resorption and for bone formation, respectively. To examine the inhibitory effects of salubrinal against pro-inflammatory cytokines, we measured TNF-α and IL1-β score in periodontium using immunohistostaining. The results revealed that salubrinal suppressed loss of alveolar bone and attachment levels in periodontium induced by periodontitis. It decreased osteoclast numbers and increased osteoblasts. It also suppressed the expression levels of TNF-α in periodontium. These results show that salubrinal alleviates periodontitis through suppression of alveolar bone resorption and the pro-inflammatory cytokine, and promotion of the bone formation. Since salubrinal has been shown to have these beneficial effects for periodontal disease, it may provide a novel therapeutic possibility for the disease.

中文翻译:


Salubrinal抑制牙周病小鼠模型中的牙槽骨吸收



内质网(ER)应激与牙周炎之间的关系已为人们所知,而内质网应激引起的牙槽骨丢失。 Salubrinal 是一种小型合成化合物,通过抑制真核翻译起始因子 2 α (eIF2α) 的去磷酸化来减轻 ER 应激。在这项研究中,我们在实验性牙周病小鼠模型中检查了 salubrinal 是否可以减轻牙周炎。我们分别使用显微计算机断层扫描(μCT)和苏木精-伊红(HE)染色评估了牙槽骨的损失和牙周组织的附着水平。此外,我们分别使用抗酒石酸酸性磷酸酶(TRAP)染色测量破骨细胞数量,并使用HE染色测量成骨细胞数量,分别用于骨吸收和骨形成。为了检查 salubrinal 对促炎细胞因子的抑制作用,我们使用免疫组织染色测量了牙周组织中的 TNF-α 和 IL1-β 评分。结果表明,salubrinal 抑制了牙周炎引起的牙槽骨和牙周组织附着水平的损失。它减少了破骨细胞的数量并增加了成骨细胞的数量。它还抑制牙周组织中 TNF-α 的表达水平。这些结果表明,Salubrinal 通过抑制牙槽骨吸收和促炎细胞因子以及促进骨形成来缓解牙周炎。由于 Salubrinal 已被证明对牙周病具有这些有益作用,因此它可能为该疾病提供一种新的治疗可能性。
更新日期:2021-09-08
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