Bmi‐1 alleviates alveolar bone resorption through the regulation of autophagy

IF 4.2 2区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Yiting Chu, Shuying Liu, Lixueer Yan, Aixiu Gong
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引用次数: 0

Abstract

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.
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)是一种关键的骨质疏松靶分子。本研究的目的是探讨 Bmi-1 对牙槽骨吸收的影响及其在体外和体内的潜在机制。方法 我们利用 Bmi-1 基因剔除(Bmi-1-/-)小鼠模型,通过微型计算机断层扫描成像、组织学和免疫组化染色,研究 Bmi-1 对牙槽骨代谢的影响。此外,我们还利用结扎诱导的实验性牙周炎模型来研究 Bmi-1 敲除(Bmi-1±)对炎性牙槽骨吸收的影响。最后,我们用脂多糖(LPS)刺激人牙周韧带干细胞(hPDLSCs),探索 Bmi-1 过表达在成骨过程中的潜在机制。结果与野生型小鼠相比,Bmi-1-/-小鼠通过抑制成骨表现出更多的牙槽骨吸收,其特征是 Runt 相关转录因子 2 和 1 型胶原形成减少。此外,Bmi-1-/-小鼠的自噬标记物(如 Parkin 和 LC3)水平较低,但牙周组织中的炎症相关因子(如白细胞介素(IL)-6 和 IL-1β)水平较高。此外,Bmi-1基因敲除会加剧结扎诱导的牙槽骨丧失。在体外炎症条件下,Bmi-1 的过表达刺激了成骨细胞的分化,抑制了炎症因子的产生,并抑制了受 LPS 刺激的 hPDLSCs 的自噬和凋亡。结论Bmi-1通过调节自噬减轻牙槽骨吸收,表明它可能是牙周炎预防和治疗的潜在靶点。目前,还缺乏有效的治疗方法来使受损的牙周组织再生。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细胞特异性莫洛尼MLV插入位点-1(Bmi-1)参与细胞周期、DNA损伤修复、自噬、骨代谢、肿瘤等生理病理过程的调控。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。结果发现,Bmi-1能调节自噬作用,保护牙周组织,这表明它可能是预防和治疗牙周炎的潜在靶点。
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来源期刊
Journal of periodontology
Journal of periodontology 医学-牙科与口腔外科
CiteScore
9.10
自引率
7.00%
发文量
290
审稿时长
3-8 weeks
期刊介绍: The Journal of Periodontology publishes articles relevant to the science and practice of periodontics and related areas.
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