Evidence map›Paper›PMID 38973294›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024

Hypoxia-Preconditioned BMSC-Derived Exosomes Induce Mitophagy via the BNIP3-ANAX2 Axis to Alleviate Intervertebral Disc Degeneration.

Yuxin Jin, Ouqiang Wu, Qizhu Chen, Linjie Chen, Zhiguang Zhang, Haijun Tian, Hao Zhou, Kai Zhang, Jianyuan Gao, Xinzhou Wang and 10 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Persistent ZnAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  6. Bone organoids and mitochondrial reprogramming.Journal of orthopaedic translation · 2026
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  16. Current research on the role of HIF in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Yuxin JinDepartment of Orthopaedics, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Ouqiang WuDepartment of Orthopaedics, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Qizhu ChenDepartment of Orthopaedics, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Linjie ChenDepartment of Orthopaedics, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Zhiguang ZhangDepartment of Orthopaedics, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Haijun TianDepartment of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
Hao ZhouDepartment of Orthopaedics, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Kai ZhangShanghai Key Laboratory of Orthopedic Implants, Department of Orthopedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Jianyuan GaoDepartment of Orthopaedics, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Xinzhou WangDepartment of Orthopaedics, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Zhenyu GuoDepartment of Orthopaedics, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Jing SunDepartment of Orthopaedics, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Kenny Yat Hong KwanDepartment of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 5/F Professorial Block, Queen Mary Hospital, 102 Pokfulam Road, Pokfulam, Hong Kong SAR, China.
Morgan JonesSpine Unit, The Royal Orthopaedic Hospital, Bristol Road South, Northfield, Birmingham, B31 2AP, UK.
Yan Michael LiThe minimaly invasive Brain and Spine Institute, Department of Neurosurgery, State University of New York Upstate medical university, 475 Irving Ave, #402, Syracuse, NY, 13210, USA.
Ehsan Nazarzadeh ZareSchool of Chemistry, Damghan University, Damghan, 36716-45667, Iran.
Pooyan MakvandiUniversity Centre for Research & Development, Chandigarh University, Mohali, Punjab, 140413, India.
Xiangyang WangDepartment of Orthopaedics, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Shuying ShenDepartment of Orthopaedics, Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province, Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.
Aimin WuDepartment of Orthopaedics, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Key Laboratory of Orthopaedics of Zhejiang Province, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.ORCID 0000-0002-8582-4599

Funding

National Natural Science Foundation of China 82272555Wenzhou Major Scientific and Technological Innovation Project ZY2022010Zhejiang Provincial Medical Technology Foundation of China 2022PY071Zhejiang Provincial Natural Science Foundation of China LGF21H060010
6 · The paper itself

Abstract

Intervertebral disc degeneration (IVDD) is a chronic degenerative disease involving the aging and loss of proliferative capacity of nucleus pulposus cells (NPCs), processes heavily dependent on mitochondrial dynamics and autophagic flux. This study finds that the absence of BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is associated with senescence-related NPC degeneration, disrupting mitochondrial quality control. Bone marrow mesenchymal stem cells (BMSCs) have multidirectional differentiation potential and produce extracellular vesicles containing cellular activators. Therefore, in this study, BMSCs are induced under hypoxic stimulation to deliver BNIP3-rich extracellular vesicles to NPCs, thereby alleviating aging-associated mitochondrial autophagic flux, promoting damaged mitochondrial clearance, and restoring mitochondrial quality control. Mechanistically, BNIP3 is shown to interact with the membrane-bound protein annexin A2 (ANXA2), enabling the liberation of the transcription factor EB (TFEB) from the ANXA2-TFEB complex, promoting TFEB nuclear translocation, and regulating autophagy and lysosomal gene activation. Furthermore, a rat model of IVDD is established and verified the in vivo efficacy of the exosomes in repairing disc injuries, delaying NPC aging, and promoting extracellular matrix (ECM) synthesis. In summary, hypoxia-induced BMSC exosomes deliver BNIP3-rich vesicles to alleviate disc degeneration by activating the mitochondrial BNIP3/ANXA2/TFEB axis, providing a new target for IVDD treatment.

Indexed as

ExosomesIntervertebral Disc DegenerationMesenchymal Stem CellsMitophagyAnimalsDisease Models, AnimalHumansHypoxiaMaleMembrane ProteinsMitochondrial ProteinsNucleus PulposusProto-Oncogene ProteinsRatsRats, Sprague-DawleyBNIP3 protein, humanBNIP3 protein, ratMembrane ProteinsMitochondrial ProteinsProto-Oncogene Proteinsbone marrow mesenchymal stem cellsexosomeshypoxia‐preconditioned mesenchymal stem cellsIntervertebral disc degenerationmatrix reconstructionmitophagy

Identifiers

PMID38973294
PMCPMC11425632

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.