• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

高血糖对PINK1/Drp1介导的线粒体自噬的抑制作用会导致糖尿病中骨生成受损。

The inhibition of PINK1/Drp1-mediated mitophagy by hyperglycemia leads to impaired osteoblastogenesis in diabetes.

作者信息

Chen Xiao-Jing, Yang Yu-Ying, Pan Zheng-Can, Xu Jing-Zun, Jiang Tao, Zhang Lin-Lin, Zhu Ke-Cheng, Zhang Deng, Song Jia-Xi, Sheng Chun-Xiang, Sun Li-Hao, Tao Bei, Liu Jian-Min, Zhao Hong-Yan

机构信息

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

iScience. 2024 Dec 3;28(1):111519. doi: 10.1016/j.isci.2024.111519. eCollection 2025 Jan 17.

DOI:10.1016/j.isci.2024.111519
PMID:39758822
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11699391/
Abstract

Impaired bone quality and increased fracture risk are cardinal features of the skeleton in diabetes mellitus. Hyperglycemia-induced oxidative stress is proposed as a potential underlying mechanism, but the precise pathogenic mechanism remains incompletely understood. In this investigation, osteoblasts under high glucose exhibited heightened levels of reactive oxygen species, impaired mitochondrial membrane potential, and profound inhibition of late-stage osteoblast differentiation. Further analyses uncovered that high glucose resulted in the downregulation of the PINK1/Drp1 pathway in osteoblasts, consequently leading to impaired mitophagy. Conversely, the upregulation of PINK1/Drp1 pathway activated mitophagy, which restored the differentiation capacity of osteoblasts. Notably, in an STZ-induced diabetic mouse model, BMP9 upregulated the expression of PINK1/Drp1 in the bone tissue, leading to an improvement in bone quality and bone mineral density. These findings suggest that the PINK1/Drp1 pathway might be a potential therapeutic target to enhance osteogenic differentiation and treat diabetic osteoporosis.

摘要

骨质量受损和骨折风险增加是糖尿病患者骨骼的主要特征。高血糖诱导的氧化应激被认为是一种潜在的潜在机制，但确切的致病机制仍未完全了解。在本研究中，高糖环境下的成骨细胞表现出活性氧水平升高、线粒体膜电位受损以及晚期成骨细胞分化受到显著抑制。进一步分析发现，高糖导致成骨细胞中PINK1/Drp1通路下调，从而导致线粒体自噬受损。相反，PINK1/Drp1通路的上调激活了线粒体自噬，恢复了成骨细胞的分化能力。值得注意的是，在链脲佐菌素诱导的糖尿病小鼠模型中，BMP9上调了骨组织中PINK1/Drp1的表达，从而改善了骨质量和骨密度。这些发现表明，PINK1/Drp1通路可能是增强成骨分化和治疗糖尿病性骨质疏松症的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/6e43c0530b31/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/8a5d15277f66/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/60b07e06697b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/97cda0201f00/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/a01d408c8b01/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/e25722b29e09/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/bd4223c512c1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/3bb0b43cc6e2/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/802897ca086d/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/ce9ed24e3b57/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/6e43c0530b31/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/8a5d15277f66/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/60b07e06697b/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/97cda0201f00/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/a01d408c8b01/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/e25722b29e09/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/bd4223c512c1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/3bb0b43cc6e2/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/802897ca086d/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/ce9ed24e3b57/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22f9/11699391/6e43c0530b31/gr9.jpg

相似文献

1
The inhibition of PINK1/Drp1-mediated mitophagy by hyperglycemia leads to impaired osteoblastogenesis in diabetes.高血糖对PINK1/Drp1介导的线粒体自噬的抑制作用会导致糖尿病中骨生成受损。
iScience. 2024 Dec 3;28(1):111519. doi: 10.1016/j.isci.2024.111519. eCollection 2025 Jan 17.
2
Activation of BK channels prevents diabetes-induced osteopenia by regulating mitochondrial Ca and SLC25A5/ANT2-PINK1-PRKN-mediated mitophagy.BK 通道的激活通过调节线粒体 Ca2+和 SLC25A5/ANT2-PINK1-PRKN 介导的线粒体自噬来预防糖尿病引起的骨质疏松症。
Autophagy. 2024 Nov;20(11):2388-2404. doi: 10.1080/15548627.2024.2367184. Epub 2024 Jun 19.
3
Inhibition of Drp1 ameliorates diabetic retinopathy by regulating mitochondrial homeostasis.抑制 Drp1 通过调节线粒体稳态改善糖尿病视网膜病变。
Exp Eye Res. 2022 Jul;220:109095. doi: 10.1016/j.exer.2022.109095. Epub 2022 Apr 28.
4
Huangkui capsule attenuates diabetic kidney disease through the induction of mitophagy mediated by STING1/PINK1 signaling in tubular cells.黄葵胶囊通过 STING1/PINK1 信号介导的小管细胞自噬来减轻糖尿病肾病。
Phytomedicine. 2023 Oct;119:154975. doi: 10.1016/j.phymed.2023.154975. Epub 2023 Jul 18.
5
PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis.PINK1 缺失通过异常的线粒体动态平衡损害成骨细胞分化。
Stem Cell Res Ther. 2021 Nov 25;12(1):589. doi: 10.1186/s13287-021-02656-4.
6
Liraglutide prevents high glucose induced HUVECs dysfunction via inhibition of PINK1/Parkin-dependent mitophagy.利拉鲁肽通过抑制 PINK1/Parkin 依赖性线粒体自噬来预防高糖诱导的 HUVECs 功能障碍。
Mol Cell Endocrinol. 2022 Apr 5;545:111560. doi: 10.1016/j.mce.2022.111560. Epub 2022 Jan 13.
7
Scutellarin ameliorates high glucose-induced vascular endothelial cells injury by activating PINK1/Parkin-mediated mitophagy.野黄芩苷通过激活 PINK1/Parkin 介导的线粒体自噬改善高糖诱导的血管内皮细胞损伤。
J Ethnopharmacol. 2021 May 10;271:113855. doi: 10.1016/j.jep.2021.113855. Epub 2021 Jan 22.
8
MK-4 Ameliorates Diabetic Osteoporosis in Angiogenesis-Dependent Bone Formation by Promoting Mitophagy in Endothelial Cells.MK-4通过促进内皮细胞中的线粒体自噬改善血管生成依赖性骨形成中的糖尿病性骨质疏松症。
Drug Des Devel Ther. 2025 Mar 25;19:2173-2188. doi: 10.2147/DDDT.S503930. eCollection 2025.
9
PINK1 phosphorylates Drp1 to regulate mitophagy-independent mitochondrial dynamics.PINK1 通过磷酸化 Drp1 调节非依赖于线粒体自噬的线粒体动力学。
EMBO Rep. 2020 Aug 5;21(8):e48686. doi: 10.15252/embr.201948686. Epub 2020 Jun 2.
10
Mesenchymal stem cells ameliorate hyperglycemia-induced endothelial injury through modulation of mitophagy.间充质干细胞通过调节细胞自噬改善高血糖引起的内皮损伤。
Cell Death Dis. 2018 Aug 6;9(8):837. doi: 10.1038/s41419-018-0861-x.

引用本文的文献

1
An emerging role of mitochondrial quality control in bone metabolism: from molecular mechanisms to targeted therapeutic interventions.线粒体质量控制在骨代谢中的新作用：从分子机制到靶向治疗干预
Cell Mol Life Sci. 2025 Jul 29;82(1):291. doi: 10.1007/s00018-025-05802-w.
2
Mitochondria: a key regulator of programmed cell death in OP.线粒体：骨质疏松症中程序性细胞死亡的关键调节因子。
Front Endocrinol (Lausanne). 2025 Jul 2;16:1576597. doi: 10.3389/fendo.2025.1576597. eCollection 2025.
3
Caffeine intake is inversely associated with osteoporosis risk based on cross-sectional and genetic evidence.

本文引用的文献

1
Neuron-targeted overexpression of caveolin-1 alleviates diabetes-associated cognitive dysfunction via regulating mitochondrial fission-mitophagy axis.神经元靶向过表达 caveolin-1 通过调节线粒体分裂-自噬轴缓解糖尿病相关认知功能障碍。
Cell Commun Signal. 2023 Dec 15;21(1):357. doi: 10.1186/s12964-023-01328-5.
2
Lipocalin 2-A bone-derived anorexigenic and β-cell promoting signal: From mice to humans.载脂蛋白 L2：一种源自于骨的致厌食和促进β细胞的信号：从老鼠到人。
J Diabetes. 2024 Mar;16(3):e13504. doi: 10.1111/1753-0407.13504. Epub 2023 Nov 30.
3
Pancreatic β-cell mitophagy as an adaptive response to metabolic stress and the underlying mechanism that involves lysosomal Ca release.
基于横断面研究和遗传学证据，咖啡因摄入量与骨质疏松症风险呈负相关。
Sci Rep. 2025 Jul 1;15(1):20720. doi: 10.1038/s41598-025-07916-4.
4
New Evidence, Creative Insights, and Strategic Solutions: Advancing the Understanding and Practice of Diabetes Osteoporosis.新证据、创新见解与战略解决方案：推动对糖尿病性骨质疏松症的理解与实践
J Diabetes. 2025 Apr;17(4):e70091. doi: 10.1111/1753-0407.70091.
胰腺β细胞线粒体自噬作为一种对代谢应激的适应性反应，其涉及溶酶体钙释放的潜在机制。
Exp Mol Med. 2023 Sep;55(9):1922-1932. doi: 10.1038/s12276-023-01055-4. Epub 2023 Sep 1.
4
Mitochondria ROS and mitophagy in acute kidney injury.线粒体 ROS 和急性肾损伤中的自噬。
Autophagy. 2023 Feb;19(2):401-414. doi: 10.1080/15548627.2022.2084862. Epub 2022 Jun 9.
5
Major osteoporosis fracture prediction in type 2 diabetes: a derivation and comparison study.2 型糖尿病患者的主要骨质疏松性骨折预测：一项推导和比较研究。
Osteoporos Int. 2022 Sep;33(9):1957-1967. doi: 10.1007/s00198-022-06425-8. Epub 2022 May 18.
6
BMP9 reduces age-related bone loss in mice by inhibiting osteoblast senescence through Smad1-Stat1-P21 axis.骨形态发生蛋白9通过Smad1-Stat1-P21轴抑制成骨细胞衰老，从而减少小鼠与年龄相关的骨质流失。
Cell Death Discov. 2022 May 6;8(1):254. doi: 10.1038/s41420-022-01048-8.
7
Mitophagy mediates metabolic reprogramming of induced pluripotent stem cells undergoing endothelial differentiation.线粒体自噬介导诱导多能干细胞向血管内皮细胞分化过程中的代谢重编程。
J Biol Chem. 2021 Dec;297(6):101410. doi: 10.1016/j.jbc.2021.101410. Epub 2021 Nov 14.
8
Glucose Metabolism in Osteoblasts in Healthy and Pathophysiological Conditions.成骨细胞在健康和病理生理条件下的葡萄糖代谢。
Int J Mol Sci. 2021 Apr 16;22(8):4120. doi: 10.3390/ijms22084120.
9
Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance.介导线粒体自噬的脂肪炎症促进伴有肝胰岛素抵抗的 2 型糖尿病。
J Exp Med. 2021 Mar 1;218(3). doi: 10.1084/jem.20201416.
10
Mitophagy protects β cells from inflammatory damage in diabetes.自噬能保护β细胞免受糖尿病炎症损伤。
JCI Insight. 2020 Dec 17;5(24):141138. doi: 10.1172/jci.insight.141138.