己糖激酶HK2激活STING通路加剧根尖周炎骨吸收

doi:10.13701/j.cnki.kqyxyj.2025.06.004

口腔医学研究 ›› 2025, Vol. 41 ›› Issue (6): 469-476.DOI: 10.13701/j.cnki.kqyxyj.2025.06.004

己糖激酶HK2激活STING通路加剧根尖周炎骨吸收

李佳琪¹, 程实^1#, 周璐^1,2, 文袁昊¹, 毛汉青¹, 张露^1,2*

1.口颌系统重建与再生全国重点实验室,口腔生物医学教育部重点实验室,口腔医学湖北省重点实验室,武汉大学口腔医学院湖北武汉 430079;
2.武汉大学口腔医院牙体牙髓科湖北武汉 430079

收稿日期:2025-03-10 出版日期:2025-06-28 发布日期:2025-06-25
通讯作者: *张露,E-mail:luzhang2012@whu.edu.cn
作者简介:李佳琪(1999~ ),女,湖南人,硕士在读,主要从事根尖周炎的免疫调控机制研究。程实(1997~ )男,内蒙古人,博士在读,主要从事根尖周炎的免疫调控机制研究。^#为共同第一作者
基金资助:
国家自然科学基金(编号:82370948、82170941)

Hexokinase HK2 Activates STING Pathway to Exacerbate Bone Resorption in Apical Periodontitis

LI Jiaqi¹, CHENG Shi^1#, ZHOU Lu^1,2, WEN Yuanhao¹, MAO Hanqing¹, ZHANG Lu^1,2*

1. State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China;
2. Department of Cariology and Endodontics, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China

Received:2025-03-10 Online:2025-06-28 Published:2025-06-25

摘要/Abstract

摘要： 目的: 探究己糖激酶2(hexokinase 2,HK2)调控根尖周炎骨吸收的分子机制。方法: 通过RNA测序分析人根尖周囊肿、肉芽肿与正常黏膜的糖酵解基因表达差异;免疫组织化学法检测HK2蛋白表达。体外实验:骨髓来源的巨噬细胞(bone marrow-derived macrophages, BMDMs)经脂多糖(lipopolysaccharide,LPS)和己糖激酶抑制剂2-脱氧-D-葡萄糖(2-deoxy-D-glucose,2DG)处理后,采用Western blot检测干扰素基因刺激蛋白(stimulator of interferon genes,STING)通路激活情况,抗酒石酸酸性磷酸酶(tartrate resistant acid phosphatase,TRAP)染色评估破骨分化能力。体内实验:建立C57/BL6小鼠根尖周炎模型并对小鼠腹腔注射2DG(14 d/28 d),通过micro-CT量化骨吸收情况,根尖周炎组织切片TRAP染色计数破骨细胞,免疫组织化学检测HK2和STING表达。结果: 人根尖周炎组织糖酵解基因显著上调,免疫组化结果显示HK2表达明显增高。2DG抑制HK2后,LPS诱导的BMDMs细胞STING表达降低23.6%(P＜0.05),破骨分化减少22.2%(P＜0.01)。动物实验显示2DG干预小鼠根尖周炎骨吸收减少,破骨细胞数量下降,STING表达降低。结论: HK2介导的糖酵解通过激活STING通路促进巨噬细胞破骨分化,抑制HK2可减轻根尖周炎骨吸收。

关键词: 根尖周炎, 糖酵解, 己糖激酶2, 干扰素基因刺激蛋白, 牙槽骨吸收

Abstract: Objective: To investigate the molecular mechanism by which hexokinase 2 (HK2) regulates bone resorption in apical periodontitis. Methods: Using RNA sequencing, the differences in glycolysis gene expression between human apical cysts/granulomas and normal mucosa were analyzed. Protein expression of HK2 was detected by immunohistochemistry. In vitro experiments: bone marrow-derived macrophages (BMDMs) were treated with lipopolysaccharides (LPS) and HK2 inhibitor 2-deoxy-D-glucose (2DG). Activation of the stimulator of interferon genes (STING) pathway was analyzed by Western blot, and osteoclast differentiation ability was assessed by tartrate resistant acid phosphatase (TRAP) staining. In vivo experiments: C57/BL6 mice were intraperitoneally injected with 2DG while establishing a periapical periodontitis model (14 days/28 days). Bone resorption was quantified by micro-CT, osteoclasts were counted by TRAP staining in apical periodontitis tissue sections, and the expressions of HK2 and STING were detected by immunohistochemistry. Results: Glycolysis-related genes were significantly up-regulated in apical periodontitis tissues. Immunohistochemical results showed that the expression of HK2 was significantly increased. After inhibition of HK2 by 2DG, the expression level of STING in LPS-induced BMDMs was decreased by 23.6% (P＜0.05), and osteoclast differentiation induced by LPS in BMDMs was reduced by 22.2% (P＜0.01). Animal experiments showed that 2DG treatment reduced the bone resorption, osteoclast number, and STING expression in mice with apical periodontitis. Conclusion: HK2-mediated glycolysis promotes macrophage osteoclastic differentiation by activating the STING signaling pathway. Inhibition of HK2 can alleviate bone resorption in apical periodontitis.

Key words: apical periodontitis, glycolysis, HK2, STING, alveolar bone resorption

李佳琪, 程实, 周璐, 文袁昊, 毛汉青, 张露. 己糖激酶HK2激活STING通路加剧根尖周炎骨吸收[J]. 口腔医学研究, 2025, 41(6): 469-476.

LI Jiaqi, CHENG Shi, ZHOU Lu, WEN Yuanhao, MAO Hanqing, ZHANG Lu. Hexokinase HK2 Activates STING Pathway to Exacerbate Bone Resorption in Apical Periodontitis[J]. Journal of Oral Science Research, 2025, 41(6): 469-476.

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己糖激酶HK2激活STING通路加剧根尖周炎骨吸收

Hexokinase HK2 Activates STING Pathway to Exacerbate Bone Resorption in Apical Periodontitis

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