Evidence map›Paper›PMID 38689463›Full record

ArticleAging cell2024

Exerkine FNDC5/irisin-enriched exosomes promote proliferation and inhibit ferroptosis of osteoblasts through interaction with Caveolin-1.

Lin Tao, Jinpeng Wang, Ke Wang, Qichang Liu, Hongyang Li, Site Xu, Chunjian Gu, Yue Zhu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 3 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

45 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Protective role of irisin on bone in osteoporosis: a systematic review of rodent studies.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025
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  6. Irisin Restrains Oligodendroglial Ferroptosis to Preserve White Matter After Traumatic Brain Injury via AMPK Activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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  11. Aging Disrupts L-type CaCirculation research · 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

8 authors.

Lin TaoDepartment of Orthopedics, First Hospital of China Medical University, Shenyang, China.
Jinpeng WangDepartment of Orthopedics, First Hospital of China Medical University, Shenyang, China.ORCID 0000-0003-4379-7403
Ke WangDepartment of Orthopedics, First Hospital of China Medical University, Shenyang, China.
Qichang LiuDepartment of Orthopedics, First Hospital of China Medical University, Shenyang, China.
Hongyang LiDepartment of Orthopedics, First Hospital of China Medical University, Shenyang, China.
Site XuDepartment of Orthopedics, First Hospital of China Medical University, Shenyang, China.
Chunjian GuDepartment of Orthopedics, First Hospital of China Medical University, Shenyang, China.
Yue ZhuDepartment of Orthopedics, First Hospital of China Medical University, Shenyang, China.

Funding

National Natural Science Foundation of China 32200943National Natural Science Foundation of China 82072387
6 · The paper itself

Abstract

Postmenopausal osteoporosis is a prevalent metabolic bone disorder characterized by a decrease in bone mineral density and deterioration of bone microstructure. Despite the high prevalence of this disease, no effective treatment for osteoporosis has been developed. Exercise has long been considered a potent anabolic factor that promotes bone mass via upregulation of myokines secreted by skeletal muscle, exerting long-term osteoprotective effects and few side effects. Irisin was recently identified as a novel myokine that is significantly upregulated by exercise and could increase bone mass. However, the mechanisms underlying exercise-induced muscle-bone crosstalk remain unclear. Here, we identified that polyunsaturated fatty acids (arachidonic acid and docosahexaenoic acid) are increased in skeletal muscles following a 10-week treadmill exercise programme, which then promotes the expression and release of FNDC5/irisin. In osteoblasts, irisin binds directly to Cav1, which recruits and interacts with AMP-activated protein kinase α (AMPKα) to activate the AMPK pathway. Nrf2 is the downstream target of the AMPK pathway and increases the transcription of HMOX1 and Fpn. HMOX1 is involved in regulating the cell cycle and promotes the proliferation of osteoblasts. Moreover, upregulation of Fpn in osteoblasts enhanced iron removal, thereby suppressing ferroptosis in osteoblasts. Additionally, we confirmed that myotube-derived exosomes are involved in the transportation of irisin and enter osteoblasts through caveolae-mediated endocytosis. In conclusion, our findings highlight the crucial role of irisin, present in myotube-derived exosomes, as a crucial regulator of exercise-induced protective effects on bone, which provides novel insights into the mechanisms underlying exercise-dependent treatment of osteoporosis.

Indexed as

Caveolin 1Cell ProliferationExosomesFibronectinsOsteoblastsAnimalsFemaleHumansMiceMuscle, SkeletalCaveolin 1FibronectinsFNDC5 protein, humanFNDC5 protein, mouseCaveolin 1exerciseexosomeferroptosisirisinosteoporosis

Identifiers

PMID38689463
PMCPMC11320359

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Registered trials

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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.