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On-line Access: 2025-12-31

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 ORCID:

Zuping WU

https://orcid.org/0000-0003-3661-8593

Qiaoli DAI

https://orcid.org/0009-0005-3273-525x

Jiejun SHI

https://orcid.org/0000-0001-6722-2909

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Journal of Zhejiang University SCIENCE B 2025 Vol.26 No.12 P.1137-1155

http://doi.org/10.1631/jzus.B2400406


Emerging roles of the metabolite succinate in bone-related diseases


Author(s):  Zuping WU, Qiaoli DAI, Ying WANG, Na WU, Chenyu WANG, Jiejun SHI

Affiliation(s):  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; more

Corresponding email(s):   sjiejun@zju.edu.cn

Key Words:  Succinate, Osteoarthritis, Rheumatoid arthritis, Osteoporosis, Fracture, Periodontitis


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Zuping WU, Qiaoli DAI, Ying WANG, Na WU, Chenyu WANG, Jiejun SHI. Emerging roles of the metabolite succinate in bone-related diseases[J]. Journal of Zhejiang University Science B, 2025, 26(12): 1137-1155.

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doi="10.1631/jzus.B2400406"
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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.

琥珀酸在骨骼相关疾病中的新兴作用

吴祖平1,2, 戴巧丽1, 王颖1, 吴娜1, 王晨宇1,施洁珺1
1浙江大学医学院附属口腔医院, 浙江大学口腔医学院, 浙江省口腔疾病临床医研究中心, 浙江省口腔生物医学研究重点实验室, 浙江大学癌症研究院, 中国杭州市, 310006
2广西口腔颌面修复与重建研究重点实验室, 中国南宁市, 530021
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。

关键词:琥珀酸;骨关节炎;类风湿性关节炎;骨质疏松;骨折;牙周炎

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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