JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Emerging role 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
Corresponding email(s): sjiejun@zju.edu.cn
Key Words: Succinate; Osteoarthritis; Rheumatoid arthritis; Osteoporosis; Periodontitis

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Zuping WU, Qiaoli DAI, Ying WANG, Na WU, Chenyu WANG, Jiejun SHI. Emerging role of the metabolite succinate in bone-related diseases[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2400406

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author="Zuping WU, Qiaoli DAI, Ying WANG, Na WU, Chenyu WANG, Jiejun SHI",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2400406"
}

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%T Emerging role of the metabolite succinate in bone-related diseases
%A Zuping WU
%A Qiaoli DAI
%A Ying WANG
%A Na WU
%A Chenyu WANG
%A Jiejun SHI
%J Journal of Zhejiang University SCIENCE B
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%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2400406"

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T1 - Emerging role of the metabolite succinate in bone-related diseases
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A1 - Qiaoli DAI
A1 - Ying WANG
A1 - Na WU
A1 - Chenyu WANG
A1 - Jiejun SHI
J0 - Journal of Zhejiang University Science B
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Y1 - in press
PB - Zhejiang University Press & Springer
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doi="https://doi.org/10.1631/jzus.B2400406"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Bone-related diseases, including osteoporosis (OP), osteoarthritis (OA), rheumatoid arthritis (RA), fractures, 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 1 alpha (HIF-1α). Moreover, it influences various pathophysiological processes by interacting with the succinate receptor (SUCNR-1), 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 impact of succinate on different bone-related diseases and to discuss potential therapeutic targets and drug molecules based on its mechanisms of action.

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