Knockout of NRAGE promotes autophagy‐related gene expression and the periodontitis process in mice

Abstract

Background and Objective Neurotrophin receptor‐interacting MAGE homologue (NRAGE) plays a crucial role in the regulation of bone metabolism. The present study investigated the regulation role of NRAGE on autophagy activation and periodontitis process during experimental periodontitis. Materials and Methods Six‐week‐old wild‐type (WT) and NRAGE−/− mice were randomly divided into three time points in the periodontitis groups (0, 2, and 4 weeks). Histopathological changes were determined using the tooth mobility, hematoxylin and eosin (H&E) staining, and micro‐computed tomography (micro‐CT). Osteoclasts activation and number were investigated using tartrate‐resistant acid phosphatase (TRAP) staining, immunohistochemistry, and real‐time quantitative PCR (RT‐PCR). The level of autophagy‐related gene expression was measured using immunohistochemistry, immunofluorescence, and RT‐PCR. Results H&E staining and Micro‐CT showed that the destruction of the alveolar bone was considerably more severe in the NRAGE−/− group than the WT group after ligation. Tooth mobility in the NRAGE−/− group was obviously higher than that in the WT group. The activation and number of osteoclasts and the level of autophagy‐related gene expression in NRAGE−/− group were significantly higher than that in WT group. Conclusions The present study showed that knockout of NRAGE induced autophagy‐related gene expression and accelerated the process of periodontitis disease via increasing the activity and differentiation of osteoclast.

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

“…Neurotrophin receptor-interacting MAGE homologue (NRAGE)-deficient mice with ligature-induced periodontitis exhibited severe alveolar bone loss compared to control mice. Knockout of NRAGE induced autophagy-related gene expression and accelerated bone destruction by increasing the activity and differentiation of osteoclasts [51].…”

An in Vitro Study of the Effect of Mage-D1 in Rat Dental Mineralization via Dynamic Histology and Ectomesenchymal Stem Cell

“…A study by Liu at el. showed that the knockdown of Mage-D1 induced autophagy-related gene expression and boosted the process of periodontitis by enhancing osteoclast activity and differentiation 23 . Therefore, we boldly speculate that the role of Mage-D1 in osteogenesis varies with cell type, which suggesting the complex and diverse roles of Mage-D1 in osteogenesis and odontogenesis.…”

“…Subsequent studies further con rmed that Mage-D1 inhibits the NF-κB signalling pathway by combining with IκB kinase β (IKKβ) 22 , which is a vital regulator of odontoblast differentiation. Liu et al showed that knocking out Mage-D1 can induce the expression of autophagy-related genes by enhancing the activity and differentiation of osteoclasts, thereby accelerating the process of periodontitis 23 . Our previous studies have shown that Mage-D1 could affect the bone differentiation ability of rat EMSCs by binding to p75NTR 5 .…”

NRAGE Confers Radiation Resistance in 2D and 3D Cell Culture and Poor Outcome in Patients With Esophageal Squamous Cell Carcinoma

“…It encodes an 86-KDa protein and is a member of the Type II MAGE family, comprising 778 amino acids (aa), of which the MAGE homology domain is common for MAGE family members and the interspersed repeat domain (IRD) is relatively unique to NRAGE for no homology to any public specific protein. These features imply that there are both uniform and specific characteristics of NRAGE compared with other members of the MAGE family (33)(34)(35)(36). Growing evidence confirmed that NRAGE functions as a transcriptional regulator mediating multiple signaling pathways from apoptosis (16,(18)(19)(20), cell differentiation (37)(38)(39), cell cycle distribution (26), cell adhesion (40), and angiogenesis (22).…”