Evidence map›Paper›PMID 38943181›Full record

ArticleJournal of orthopaedic surgery and research2024

Platelet-derived exosomes alleviate tendon stem/progenitor cell senescence and ferroptosis by regulating AMPK/Nrf2/GPX4 signaling and improve tendon-bone junction regeneration in rats.

Deheng Chen, Qian Tang, Wei Song, Yaohua He

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Article in Journal of orthopaedic surgery and research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
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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

16 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  4. [Research progress on extracellular vesicles derived from platelet-rich plasma in tissue repair and regeneration].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026
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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

4 authors.

Deheng ChenDepartment of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University of Medicine, 600 Yishan Road, Shanghai, 200233, China.
Qian TangDepartment of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University of Medicine, 600 Yishan Road, Shanghai, 200233, China.
Wei SongDepartment of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University of Medicine, 600 Yishan Road, Shanghai, 200233, China.
Yaohua HeDepartment of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University of Medicine, 600 Yishan Road, Shanghai, 200233, China. heyaohua@sjtu.edu.cn.

Funding

National Natural Science Foundation of China 82072401, 81871755the Program of Shanghai Academic/Technology Research Leader 19XD1402800
6 · The paper itself

Abstract

backgroundTendon stem/progenitor cell (TSPC) senescence contributes to tendon degeneration and impaired tendon repair, resulting in age-related tendon disorders. Ferroptosis, a unique iron-dependent form of programmed cell death, might participate in the process of senescence. However, whether ferroptosis plays a role in TSPC senescence and tendon regeneration remains unclear. Recent studies reported that Platelet-derived exosomes (PL-Exos) might provide significant advantages in musculoskeletal regeneration and inflammation regulation. The effects and mechanism of PL-Exos on TSPC senescence and tendon regeneration are worthy of further study.

methodsHerein, we examined the role of ferroptosis in the pathogenesis of TSPC senescence. PL-Exos were isolated and determined by TEM, particle size analysis, western blot and mass spectrometry identification. We investigated the function and underlying mechanisms of PL-Exos in TSPC senescence and ferroptosis via western blot, real-time quantitative polymerase chain reaction, and immunofluorescence analysis in vitro. Tendon regeneration was evaluated by HE staining, Safranin-O staining, and biomechanical tests in a rotator cuff tear model in rats.

resultsWe discovered that ferroptosis was involved in senescent TSPCs. Furthermore, PL-Exos mitigated the aging phenotypes and ferroptosis of TSPCs induced by t-BHP and preserved their proliferation and tenogenic capacity. The in vivo animal results indicated that PL-Exos improved tendon-bone healing properties and mechanical strength. Mechanistically, PL-Exos activated AMPK phosphorylation and the downstream nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway, leading to the suppression of lipid peroxidation. AMPK inhibition or GPX4 inhibition blocked the protective effect of PL-Exos against t-BHP-induced ferroptosis and senescence.

conclusionIn conclusion, ferroptosis might play a crucial role in TSPC aging. AMPK/Nrf2/GPX4 activation by PL-Exos was found to inhibit ferroptosis, consequently leading to the suppression of senescence in TSPCs. Our results provided new theoretical evidence for the potential application of PL-Exos to restrain tendon degeneration and promote tendon regeneration.

Indexed as

AMP-Activated Protein KinasesCellular SenescenceExosomesFerroptosisNF-E2-Related Factor 2Phospholipid Hydroperoxide Glutathione PeroxidaseRegenerationSignal TransductionStem CellsTendonsAnimalsBlood PlateletsDisease Models, AnimalMaleRatsRats, Sprague-DawleyAMP-Activated Protein Kinasesglutathione peroxidase 4, ratNfe2l2 protein, ratNF-E2-Related Factor 2Phospholipid Hydroperoxide Glutathione PeroxidaseAMPK/Nrf2/GPX4FerroptosisPlatelet-derived exosomesSenescence

Identifiers

PMID38943181
PMCPMC11212425

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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.