Evidence map›Paper›PMID 40652239›Full record

ArticleJournal of nanobiotechnology2025

FNDC5/irisin-enriched sEVs conjugated with bone-targeting aptamer alleviate osteoporosis: a potential alternative to exercise.

Min-Zhi Mao, Ming-Hui Zheng, Bei Guo, Ya-Li Ling, Xiao Lin, Fu-Xing-Zi Li, Su-Kang Shan, De-Xing Dai, Lei Qiu, Xue-Yang Cai and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of nanobiotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–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

11 citing papers in PubMed.

  1. Glucose metabolism in osteoporosis: A potential therapeutic target (Review).International journal of molecular medicine · 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

25 authors.

Min-Zhi Mao *Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
Ming-Hui Zheng *Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Bei GuoDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Ya-Li LingDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Xiao LinDepartment of Radiology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
Fu-Xing-Zi LiDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Su-Kang ShanDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
De-Xing DaiDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Lei QiuDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Xue-Yang CaiDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Ya DingDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Ying-Ying GuDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Qi-Rong DengDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Zhi-Ang ZhouDepartment of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
Li-Min LeiDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Cheng TaoDepartment of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
Rong-Rong CuiDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Feng WuDepartment of Pathology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
Fei ZhangDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Bo WuDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China.
Le-Le LiaoDepartment of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
Chang-Ming TanDepartment of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
Xiao-Bo LiaoDepartment of Cardiothoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
Ling-Qing YuanDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China. allenylq@csu.edu.cn.
Feng XuDepartment of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha, 410011, Hunan, China. feng.xu@csu.edu.cn.

Funding

Fundamental Research Funds for the Central Universities of Central South University 2025ZZTS0147Fundamental Research Funds for the Central Universities of Central South University 2025ZZTS0807Health Research Project of Hunan Provincial Health Commission 202103062278National Natural Science Foundation of China 82070910National Natural Science Foundation of China 82100494National Natural Science Foundation of China 82200869National Natural Science Foundation of China 82470927Natural Science Foundation of Hunan Province 2021JJ40875Natural Science Foundation of Hunan Province 2022JJ30799Natural Science Foundation of Hunan Province 2022JJ30826Natural Science Foundation of Hunan Province 2022JJ70055Natural Science Foundation of Hunan Province 2022JJ70140Natural Science Foundation of Hunan Province 2025JJ40097Scientific Research Launch Project for new employees of the Second Xiangya Hospital of Central South University 7673
6 · The paper itself

Abstract

Exercise maintains bone health and produces protective effects on bone loss. In this study, we investigated the potential protective effects of circulating small extracellular vesicles (sEVs) generated under endurance exercise training (Exe-sEVs) on ovariectomized (OVX)-induced bone loss. Inhibition of sEVs secretion by GW4869 partially reversed exercised-induced protection against OVX-induced bone loss. Importantly, Exe-sEVs was internalized by bone tissue and alleviated bone loss in OVX-mice. The increased levels of fibronectin type-III domain-containing protein 5 (FNDC5/irisin) in Exe-sEVs contributed to the promotion of osteogenesis in bone marrow mesenchymal stem cells (BM-MSCs). However, systemic knockdown of FNDC5, the precursor of irisin, abolished the exercise-induced protective effects against bone loss in OVX-mice. Moreover, incubation of irisin enhanced osteogenesis and attenuated adipogenesis in BM-MSCs. Intriguingly, implantation of BM-MSCs overexpressing FNDC5 accelerated osteogenesis and chondrogenesis in BALB/c immunodeficiency mice. Mechanistically, irisin promoted phosphorylation of p38MAPK and JNK, but not ERK. Blocking the JNK and p38MAPK signaling pathway with specific inhibitors abolished the pro-osteogenesis and anti-adipogenesis effects of irisin on BM-MSCs. However, inhibition of β-arrestin-2 rescued the irisin-induced activation of p38MAPK and JNK. Finally, aptamer-modified FNDC5-sEVs (Apt-FNDC5-sEVs) exhibited higher enrichment in bone tissues and enhanced bone formation. In conclusion, exercise-induced circulating FNDC5/irisin-enriched sEVs promote osteogenesis of mouse BM-MSCs both in vitro and in vivo, partially through a β-arrestin-2-dependent p38MAPK and JNK signaling pathway. Apt-FNDC5-sEVs represent a promising strategy for the treatment of osteoporosis.

Indexed as

Aptamers, NucleotideExtracellular VesiclesFibronectinsOsteoporosisAnimalsBone and BonesFemaleHumansMesenchymal Stem CellsMiceMice, Inbred BALB COsteogenesisOvariectomyPhysical Conditioning, AnimalAptamers, NucleotideFibronectinsFNDC5 protein, mouseAptamerBone marrow mesenchymal stem cellsExerciseFNDC5/irisinOsteoporosisSmall extracellular vesicles

Identifiers

PMID40652239
PMCPMC12255020

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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.