Acid α-Glucosidase Impairs Diabetic Bone Regeneration via Altering Macrophage Polarization.

IF 5.9 1区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Dental Research Pub Date : 2025-09-09 DOI:10.1177/00220345251350658

S C Yu,J F Liang,Y Li,S Y Ma,J Sun,A Li,D D Pei

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引用次数: 0

Abstract

The diabetic microenvironment intensifies M1-type macrophage-mediated inflammation and impairs bone regeneration. Glycophagy-a process of glycogen-selective autophagy that degrades intracellular glycogen into glucose-is essential for maintaining glucose homeostasis under metabolic stress. The role of glycophagy in regulating M1-type polarization remains unclear. In this study, we found that M1-type polarization correlated with increased glycophagy in a diabetic mandibular bone defect model. Proteomic analysis revealed the involvement of the glycophagy mediator acid α-glucosidase (GAA) in M1-type polarization in diabetic bone callus. Mechanistically, the upregulation of GAA drove M1-type polarization to inhibit osteogenesis under high-glucose conditions by activating the mTORC1 signaling pathway. Transplant of GAA-silenced macrophages restored the osteogenic capability in mandibular injury in diabetic rats. In conclusion, our study unravels the regulation of a fundamental mechanism of M1-type polarization by the glycophagy mediator GAA, providing insights relevant for promoting bone generation in diabetic individuals.

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酸性α-葡萄糖苷酶通过改变巨噬细胞极化损害糖尿病骨再生。

糖尿病微环境加剧了m1型巨噬细胞介导的炎症，损害了骨再生。糖吞噬是一种糖原选择性自噬过程，可将细胞内糖原降解为葡萄糖，是代谢应激下维持葡萄糖稳态所必需的。糖吞噬在调节m1型极化中的作用尚不清楚。在本研究中，我们发现m1型极化与糖尿病下颌骨缺损模型中糖吞噬增加相关。蛋白质组学分析显示糖吞噬介质α-葡萄糖苷酶（GAA）参与糖尿病骨愈伤组织m1型极化。在机制上，GAA的上调通过激活mTORC1信号通路，驱动m1型极化抑制高糖条件下的成骨。移植gaa沉默巨噬细胞恢复糖尿病大鼠下颌骨损伤的成骨能力。总之，我们的研究揭示了糖吞噬介质GAA对m1型极化的基本调控机制，为促进糖尿病患者骨生成提供了相关见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Dental Research 医学-牙科与口腔外科

CiteScore

15.30

自引率

3.90%

发文量

155

审稿时长

3-8 weeks

期刊介绍： The Journal of Dental Research (JDR) is a peer-reviewed scientific journal committed to sharing new knowledge and information on all sciences related to dentistry and the oral cavity, covering health and disease. With monthly publications, JDR ensures timely communication of the latest research to the oral and dental community.