SDF-1 alleviates osteoarthritis by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathway

Abstract Objective Osteoarthritis (OA) is the most common form of joint disease. Currently, OA treatment is limited to controlling symptoms. Our previous study showed that stromal cell-derived factor 1 (SDF-1) delayed the progression of OA to a certain extent. The aim of this study was to explore th...

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Main Authors: Yanping Zhao, Dan Lin, Xiaoying Zhu, Jingyao Yan, Yan Liang, Yanli Wang, Tianqi Dai, Zhiyi Zhang, Shuya Wang
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Arthritis Research & Therapy
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Online Access:https://doi.org/10.1186/s13075-025-03509-8
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author Yanping Zhao
Dan Lin
Xiaoying Zhu
Jingyao Yan
Yan Liang
Yanli Wang
Tianqi Dai
Zhiyi Zhang
Shuya Wang
author_facet Yanping Zhao
Dan Lin
Xiaoying Zhu
Jingyao Yan
Yan Liang
Yanli Wang
Tianqi Dai
Zhiyi Zhang
Shuya Wang
author_sort Yanping Zhao
collection DOAJ
description Abstract Objective Osteoarthritis (OA) is the most common form of joint disease. Currently, OA treatment is limited to controlling symptoms. Our previous study showed that stromal cell-derived factor 1 (SDF-1) delayed the progression of OA to a certain extent. The aim of this study was to explore the specific mechanism of SDF-1 in OA. Materials and methods OA chondrocytes and a collagen-induced osteoarthritis (CIOA) mouse model were used as in vitro and in vivo models, respectively. SDF-1 was used to treat OA in vitro and in vivo. To explore the mechanism of SDF-1 in OA treatment, we pretreated chondrocytes with a Sirt 3 inhibitor and assessed mitochondrial function and then analysed related indicators of cartilage anabolic and cartilage metabolism. Results SOD2 and PGC-1α levels were significantly lower in OA chondrocytes and the cartilage of CIOA model mice than in normal chondrocytes, and mitochondrial dysfunction occurred in OA. After treating OA chondrocytes and CIOA model mice with exogenous SDF-1, mitochondrial dysfunction and abnormal biomarkers of OA normalized. The pretreatment of OA chondrocytes with a Sirt 3 inhibitor or mitochondrial function inhibitor before SDF-1 exposure reversed these changes. Conclusions SDF-1 can alleviate OA by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathway, and therefore, SDF-1 may be a good candidate as a new treatment for OA.
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spelling doaj-art-1f22c17fca3e481d91b4ddb1a2977bb52025-08-20T01:57:52ZengBMCArthritis Research & Therapy1478-63622025-03-012711910.1186/s13075-025-03509-8SDF-1 alleviates osteoarthritis by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathwayYanping Zhao0Dan Lin1Xiaoying Zhu2Jingyao Yan3Yan Liang4Yanli Wang5Tianqi Dai6Zhiyi Zhang7Shuya Wang8Department of Rheumatology, The Affiliated hospital of Harbin Medical UniversityDepartment of Rheumatology, The Affiliated hospital of Harbin Medical UniversityDepartment of Rheumatology, The Affiliated hospital of Harbin Medical UniversityDepartment of Rheumatology, The Affiliated hospital of Harbin Medical UniversityDepartment of Rheumatology, The Affiliated hospital of Harbin Medical UniversityDepartment of Rheumatology, The Affiliated hospital of Harbin Medical UniversityDepartment of Rheumatology, The Affiliated hospital of Harbin Medical UniversityDepartment of Rheumatology, The Affiliated hospital of Harbin Medical UniversityDepartment of Rheumatology, The Affiliated hospital of Harbin Medical UniversityAbstract Objective Osteoarthritis (OA) is the most common form of joint disease. Currently, OA treatment is limited to controlling symptoms. Our previous study showed that stromal cell-derived factor 1 (SDF-1) delayed the progression of OA to a certain extent. The aim of this study was to explore the specific mechanism of SDF-1 in OA. Materials and methods OA chondrocytes and a collagen-induced osteoarthritis (CIOA) mouse model were used as in vitro and in vivo models, respectively. SDF-1 was used to treat OA in vitro and in vivo. To explore the mechanism of SDF-1 in OA treatment, we pretreated chondrocytes with a Sirt 3 inhibitor and assessed mitochondrial function and then analysed related indicators of cartilage anabolic and cartilage metabolism. Results SOD2 and PGC-1α levels were significantly lower in OA chondrocytes and the cartilage of CIOA model mice than in normal chondrocytes, and mitochondrial dysfunction occurred in OA. After treating OA chondrocytes and CIOA model mice with exogenous SDF-1, mitochondrial dysfunction and abnormal biomarkers of OA normalized. The pretreatment of OA chondrocytes with a Sirt 3 inhibitor or mitochondrial function inhibitor before SDF-1 exposure reversed these changes. Conclusions SDF-1 can alleviate OA by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathway, and therefore, SDF-1 may be a good candidate as a new treatment for OA.https://doi.org/10.1186/s13075-025-03509-8OsteoarthritisStromal cell-derived factor 1Mitochondrial dysfunctionChondrocyteSirt3
spellingShingle Yanping Zhao
Dan Lin
Xiaoying Zhu
Jingyao Yan
Yan Liang
Yanli Wang
Tianqi Dai
Zhiyi Zhang
Shuya Wang
SDF-1 alleviates osteoarthritis by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathway
Arthritis Research & Therapy
Osteoarthritis
Stromal cell-derived factor 1
Mitochondrial dysfunction
Chondrocyte
Sirt3
title SDF-1 alleviates osteoarthritis by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathway
title_full SDF-1 alleviates osteoarthritis by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathway
title_fullStr SDF-1 alleviates osteoarthritis by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathway
title_full_unstemmed SDF-1 alleviates osteoarthritis by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathway
title_short SDF-1 alleviates osteoarthritis by resolving mitochondrial dysfunction through the activation of the Sirt3/PGC-1α signalling pathway
title_sort sdf 1 alleviates osteoarthritis by resolving mitochondrial dysfunction through the activation of the sirt3 pgc 1α signalling pathway
topic Osteoarthritis
Stromal cell-derived factor 1
Mitochondrial dysfunction
Chondrocyte
Sirt3
url https://doi.org/10.1186/s13075-025-03509-8
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