Suppression of alveolar bone resorption by salubrinal in a mouse model of periodontal disease
Suppression of alveolar bone resorption by salubrinal in a mouse model of periodontal disease
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DOI：
10.1016/j.lfs.2021.119938
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发表时间：
2021-09-09
期刊：
影响因子：
6.1
通讯作者：
Goto, Shigemi
中科院分区：
文献类型：
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作者：
Kimura, Fumika;Miyazawa, Ken;Goto, Shigemi
目的：内质网（ER）应激与牙周炎的关系已被人们所知，牙龈卟啉单胞菌（Porphyromonas gingivalis）诱导的ER应激导致牙槽骨的丢失。Salubrinal是一种小的合成化合物，通过抑制真核翻译起始因子2 α（eIF 2 α）的去磷酸化来减弱ER应激。在这项研究中，我们研究是否salubrinal减轻牙周炎的实验性牙周病的小鼠模型。材料与方法：我们分别使用微计算机断层扫描（mu CT）和苏木精-伊红（HE）染色评估牙槽骨和牙周组织附着水平的丧失。此外，我们测量破骨细胞的数量使用抗酒石酸酸性磷酸酶（TRAP）染色和成骨细胞的数量使用HE染色的骨吸收和骨形成，分别。为了检测salubrinal对促炎细胞因子的抑制作用，我们使用MTT染色测量了牙周组织中TNF-α和IL 1-β的评分。主要发现：结果显示，salubrinal抑制牙周炎引起的牙槽骨和牙周组织附着水平的丧失。它减少破骨细胞的数量，增加成骨细胞。它还抑制牙周组织中TNF-α的表达水平。重要性：这些结果表明，salubrinal通过抑制牙槽骨吸收和促炎细胞因子，促进骨形成来减轻牙周炎。由于salubrinal已被证明对牙周病有这些有益的效果，它可能为该疾病提供一种新的治疗可能性。
Aims: The relationship between stress to endoplasmic reticulum (ER) and periodontitis has been known, and ER stress induced by Porphyromonas gingivalis 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 (eIF2 alpha). In this study, we examined whether salubrinal attenuates periodontitis in a mouse model of experimental periodontal disease. Materials and methods: We evaluated loss of alveolar bone and attachment levels in periodontium using microcomputed tomography (mu CT) 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-alpha and IL1-beta score in periodontium using immunohistostaining. Key findings: 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-alpha in periodontium. Significance: 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.