Reprogramming of Mitochondrial Respiratory Chain Complex by Targeting SIRT3‐COX4I2 Axis Attenuates Osteoarthritis Progression
Abstract: Mitochondrial homeostasis is of great importance for cartilage integrity and associated with the progression of osteoarthritis (OA); however, the underlying mechanisms are unknown. This study aims to investigate the role of mitochondrial deacetylation reaction and investigate the mechanistic relationship OA development. Silent mating type information regulation 2 homolog 3 (SIRT3) expression has a negative correlation with the severity of OA in both human arthritic cartilage and mice inflammatory chondrocytes. Global SIRT3 deletion accelerates pathological phenotype in post‐traumatic OA mice, as evidenced by cartilage extracellular matrix collapse, osteophyte formation, and synovial macrophage M1 polarization. Mechanistically, SIRT3 prevents OA progression by targeting and deacetylating cytochrome c oxidase subunit 4 isoform 2 (COX4I2) to maintain mitochondrial homeostasis at the post‐translational level. The activation of SIRT3 by honokiol restores cartilage metabolic equilibrium and protects mice from the development of post‐traumatic OA. Collectively, the loss of mitochondrial SIRT3 is essential for the development of OA, whereas SIRT3‐mediated proteins deacetylation of COX4I2 rescues OA‐impaired mitochondrial respiratory chain functions to improve the OA phenotype. Herein, the induction of SIRT3 provides a novel therapeutic candidate for OA treatment.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Reprogramming of Mitochondrial Respiratory Chain Complex by Targeting SIRT3‐COX4I2 Axis Attenuates Osteoarthritis Progression ; day:22 ; month:01 ; year:2023 ; extent:14
Advanced science ; (22.01.2023) (gesamt 14)
- Creator
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Zhang, Yijian
Liu, Yang
Hou, Mingzhuang
Xia, Xiaowei
Liu, Junlin
Xu, Yong
Shi, Qin
Zhang, Zhongmin
Wang, Liang
Shen, Yifan
Yang, Huilin
He, Fan
Zhu, Xuesong
- DOI
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10.1002/advs.202206144
- URN
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urn:nbn:de:101:1-2023012314153599274007
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:22 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Zhang, Yijian
- Liu, Yang
- Hou, Mingzhuang
- Xia, Xiaowei
- Liu, Junlin
- Xu, Yong
- Shi, Qin
- Zhang, Zhongmin
- Wang, Liang
- Shen, Yifan
- Yang, Huilin
- He, Fan
- Zhu, Xuesong
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Reprogramming of Mitochondrial Respiratory Chain Complex by Targeting SIRT3‐COX4I2 Axis Attenuates Osteoarthritis Progression (Adv. Sci. 10/2023)
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Value of serial cervical length measurement in prediction of spontaneous preterm birth in post-conization pregnancy without short mid-trimester cervix
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