BackgroundB‐cell‑specific Moloney MLV insertion site‐1(Bmi‐1)is a crucial osteopenic target molecule. The aim of this study is to explore the effects of Bmi‐1 on alveolar bone resorption and the underlying mechanisms in vitro and vivo.MethodsA Bmi‐1‐knockout (Bmi‐1−/−) mouse model was used to investigate the effect of Bmi‐1 on alveolar bone metabolism, with micro‐computed tomography imaging, histology, and immunohistochemistry staining. Furthermore, we utilized a ligature‐induced experimental periodontitis model to examine the impact of Bmi‐1‐knockdown (Bmi‐1±) on inflammatory alveolar bone resorption. Finally, we stimulated human periodontal ligament stem cells (hPDLSCs) with lipopolysaccharide (LPS) to explore the potential mechanism of Bmi‐1 overexpression in the process of osteogenesis.ResultsCompared with wild‐type mice, Bmi‐1−/− mice demonstrated more alveolar bone resorption by inhibiting osteogenesis, which was characterized by decreases in Runt‐related transcription factor 2 and type 1 collagen formation. In addition, Bmi‐1−/− mice had lower levels of autophagy markers such as Parkin and LC3, but higher levels of inflammation‐related factors such as interleukin (IL)‐6 and IL‐1β in periodontal tissues. In addition, Bmi‐1‐knockdown aggravated ligature‐induced alveolar bone loss. Under in vitro inflammatory conditions, Bmi‐1 overexpression stimulated osteoblast differentiation and inhibited the production of inflammatory factors, as well as the autophagy and apoptosis in hPDLSCs stimulated with LPS. When 3‐methyladenine (3‐MA), an autophagy inhibitor, was added, the osteogenic effect of Bmi‐1 was further enhanced.ConclusionsBmi‐1 alleviates alveolar bone resorption by regulating autophagy, indicating that it could be a potential target for periodontitis prevention and treatment.Plain Language SummaryPeriodontitis is a chronic inflammatory disease, which leads to progressive destruction of periodontal tissues, manifested as periodontal pocket formation, loss of periodontal attachment and alveolar bone resorption. Currently, there is a lack of effective treatments to regenerate damaged periodontal tissues. Therefore, it is of great clinical significance to explore new mechanisms of periodontitis and effective intervention targets. B‐cell‑specific Moloney MLV insertion site‐1 (Bmi‐1) is involved in the regulation of the cell cycle, DNA damage repair, autophagy, bone metabolism, tumor, and other physiopathological processes. Autophagy, as an important mechanism of intracellular self‐regulation, plays an indispensable role in the destruction and repair of periodontal tissues. The aim of this study was to investigate the role of Bmi‐1 on periodontal tissues and its intrinsic mechanism. The results revealed that Bmi‐1 regulates autophagy to protect periodontal tissues, suggesting that it may be a potential target for the prevention and treatment of periodontitis.

中文翻译：

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Bmi-1通过调节自噬减轻牙槽骨吸收


背景B细胞特异性莫洛尼MLV插入位点-1（Bmi-1）是一种重要的骨质减少靶分子。本研究的目的是探讨Bmi-1对牙槽骨吸收的影响及其体内外机制。方法采用Bmi-1敲除（Bmi-1−/−）小鼠模型来研究Bmi-1对牙槽骨吸收的影响。 Bmi-1 对牙槽骨代谢的影响，包括微型计算机断层扫描成像、组织学和免疫组织化学染色。此外，我们利用结扎诱导的实验性牙周炎模型来研究 Bmi-1 敲低 (Bmi-1±) 对炎症性牙槽骨吸收的影响。最后，我们用脂多糖（LPS）刺激人牙周膜干细胞（hPDLSC），探讨Bmi-1在成骨过程中过表达的潜在机制。结果与野生型小鼠相比，Bmi-1−/−小鼠表现出更多的牙槽骨通过抑制成骨来促进骨吸收，其特点是 Runt 相关转录因子 2 和 1 型胶原形成减少。此外，Bmi-1−/− 小鼠牙周组织中 Parkin 和 LC3 等自噬标记物水平较低，但白细胞介素 (IL)-6 和 IL-1β 等炎症相关因子水平较高。此外，Bmi-1 敲低加剧了结扎引起的牙槽骨丢失。在体外炎症条件下，Bmi-1过表达刺激成骨细胞分化并抑制炎症因子的产生，以及LPS刺激的hPDLSCs的自噬和凋亡。当添加自噬抑制剂3-甲基腺嘌呤（3-MA）时，Bmi-1的成骨作用进一步增强。结论 Bmi-1通过调节自噬减轻牙槽骨吸收，可能成为牙周炎防治的潜在靶点。 通俗小结牙周炎是一种慢性炎症性疾病，导致牙周组织进行性破坏，表现为牙周袋形成、牙周袋脱落等。牙周附着和牙槽骨吸收。目前，缺乏有效的治疗方法来再生受损的牙周组织。因此，探索牙周炎的新机制和有效的干预靶点具有重要的临床意义。 B 细胞特异性 Moloney MLV 插入位点 1 (Bmi-1) 参与细胞周期的调节、DNA 损伤修复、自噬、骨代谢、肿瘤和其他病理生理过程。自噬作为细胞内自我调节的重要机制，在牙周组织的破坏和修复中发挥着不可或缺的作用。本研究旨在探讨Bmi-1对牙周组织的作用及其内在机制。结果显示，Bmi-1通过调节自噬来保护牙周组织，提示其可能成为预防和治疗牙周炎的潜在靶点。