Emerging roles of the metabolite succinate in bone-related diseases

Zuping WU; Qiaoli DAI; Ying WANG; Na WU; Chenyu WANG; Jiejun SHI

doi:10.1631/jzus.B2400406

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Review | Updated：2025-12-31

Emerging roles of the metabolite succinate in bone-related diseases
Emerging roles of the metabolite succinate in bone-related diseases
琥珀酸在骨骼相关疾病中的新兴作用
Journal of Zhejiang University-SCIENCE B Vol. 26, Issue 12, Pages: 1137-1155(2025)
Affiliations：

1.Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310016, China
2.Guangxi Key Laboratory of the Rehabilitation and Reconstruction for Oral and Maxillofacial Research, Nanning 530021, China
Funds：
DOI：10.1631/jzus.B2400406
CLC：
CSTR：
Received：08 August 2024，

Revised：2024-11-19，

Published Online：10 December 2025，

Published：31 December 2025
Accepted：

吴祖平,戴巧丽,王颖等.琥珀酸在骨骼相关疾病中的新兴作用[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(12):1137-1155.

Zuping WU, Qiaoli DAI, Ying WANG, et al. Emerging roles of the metabolite succinate in bone-related diseases[J]. Journal of Zhejiang University-SCIENCE B, 2025, 26(12): 1137-1155.
吴祖平,戴巧丽,王颖等.琥珀酸在骨骼相关疾病中的新兴作用[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(12):1137-1155. DOI： 10.1631/jzus.B2400406.

Zuping WU, Qiaoli DAI, Ying WANG, et al. Emerging roles of the metabolite succinate in bone-related diseases[J]. Journal of Zhejiang University-SCIENCE B, 2025, 26(12): 1137-1155. DOI： 10.1631/jzus.B2400406.

摘要

包括骨质疏松症、骨关节炎、类风湿性关节炎、骨折和牙周炎在内的骨相关疾病，显著影响了人类健康。琥珀酸作为三羧酸循环中的一种代谢中间产物，已被发现不仅在代谢中起作用，还能作为细胞功能的调节因子发挥作用。应激状态下，琥珀酸在线粒体中积累，作为信号分子调节细胞功能。值得注意的是，琥珀酸可通过稳定缺氧诱导因子1α（HIF-1α）促进血管生成和炎症发展。此外，琥珀酸还可通过与琥珀酸受体1（SUCNR1）作用介导多种病理生理过程，如免疫反应、炎症、癌症转移和骨稳态等。琥珀酸作为信号分子的多重作用取决于其在细胞中的位置和浓度。近期的代谢组学分析发现，骨相关疾病中琥珀酸水平升高，提示其可能与这些疾病相关。本综述旨在阐明琥珀酸对不同骨相关疾病的影响，并基于其作用机制探讨潜在的治疗靶点和相关药物分子。

Abstract

Bone-related diseases

including osteoporosis (OP)

osteoarthritis (OA)

rheumatoid arthritis (RA)

fracture

and periodontitis

significantly impact human health. Succinate

primarily known as a metabolic intermediate in the tricarboxylic acid (TCA) cycle

has emerged as a regulator of cellular functions beyond its metabolic role. Under stress

succinate accumulates in mitochondria and acts as a signaling molecule

modulating cellular processes. Notably

succinate activates angiogenesis and inflammation by stabilizing hypoxia-inducible factor-1α (HIF-1α). Moreover

it influences various pathophysiological processes by interacting with the succinate receptor 1 (SUCNR1)

thereby impacting immune response

inflammation

cancer metastasis

and bone homeostasis. The multifaceted roles of succinate as a signaling molecule vary depending on its cellular location and concentration. Recent metabolomic analyses have revealed elevated succinate levels in bone-related diseases

indicating its potential association with these conditions. The objective of this review is to elucidate the impacts of succinate on different bone-related diseases and to discuss potential therapeutic targets and drug molecules based on its mechanisms of action.

关键词

Keywords

references

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Related Institution

Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Zhejiang Key Laboratory of Oral Biomedical, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province

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