Evidence map›Paper›PMID 34596354›Full record

ArticleJournal of extracellular vesicles2021

Extracellular vesicles from adipose tissue-derived stem cells alleviate osteoporosis through osteoprotegerin and miR-21-5p.

Kyoung Soo Lee, Jeongmi Lee, Hark Kyun Kim, Seung Ho Yeom, Chang Hee Woo, Youn Jae Jung, Ye Eun Yun, So Young Park, Jihoon Han, Eunae Kim and 6 more

Open access · goldAbstract read
In one paragraph

Article in Journal of extracellular vesicles, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
124citing papers in PubMed, 2 pooled it
10.4field-weighted citation impact, top 1% of its field
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

124 citing papers in PubMed, 2 syntheses or guidelines pooled it, 189 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Extracellular vesicle-mediated crosstalk in bone: miR-150-5p as a mechanosensitive regulator of osteoclastogenesis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  5. Review
  6. Article
  7. Article
  8. Application and prospects of nanomaterials in osteoporosis treatment.International journal of pharmaceutics: X · 2026
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Extracellular vesicles inEXO : beyond the cell · 2026
    Article
  19. Review
  20. Review

64 more citing papers are in PubMed but not listed here.

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

16 authors at 3 institutions in 2 countries.

Kyoung Soo LeeDepartment of Materials Science and Chemical Engineering, Hanyang University ERICA, Ansan, Korea.ORCID 0000-0002-3494-0290
Jeongmi LeeSchool of Pharmacy, Sungkyunkwan University, Suwon, Korea.ORCID 0000-0002-4134-5713
Hark Kyun KimSchool of Pharmacy, Sungkyunkwan University, Suwon, Korea.ORCID 0000-0003-2755-0806
Seung Ho YeomExostemtech, Inc., Ansan, Korea.ORCID 0000-0003-4101-2190
Chang Hee WooExostemtech, Inc., Ansan, Korea.ORCID 0000-0003-2365-3269
Youn Jae JungExostemtech, Inc., Ansan, Korea.ORCID 0000-0002-4238-9371
Ye Eun YunDepartment of Materials Science and Chemical Engineering, Hanyang University ERICA, Ansan, Korea.ORCID 0000-0001-9676-1020
So Young ParkExostemtech, Inc., Ansan, Korea.ORCID 0000-0002-3461-8525
Jihoon HanSchool of Pharmacy, Sungkyunkwan University, Suwon, Korea.ORCID 0000-0001-5870-1414
Eunae KimSchool of Pharmacy, Sungkyunkwan University, Suwon, Korea.ORCID 0000-0002-8930-8882
Jae Hoon SulSchool of Pharmacy, Sungkyunkwan University, Suwon, Korea.ORCID 0000-0002-0862-7057
Jae Min JungSchool of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon, Korea.ORCID 0000-0003-0819-7226
Jae Hyung ParkExostemtech, Inc., Ansan, Korea.ORCID 0000-0002-5043-9455
Ji Suk ChoiExostemtech, Inc., Ansan, Korea.ORCID 0000-0002-2351-0316
Yong Woo ChoDepartment of Materials Science and Chemical Engineering, Hanyang University ERICA, Ansan, Korea.ORCID 0000-0002-2075-4147
Dong-Gyu JoExostemtech, Inc., Ansan, Korea.ORCID 0000-0003-2271-1076
Neostem (United States) · USSungkyunkwan University · KRHanyang University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteoporosis is one of the most common skeletal disorders caused by the imbalance between bone formation and resorption, resulting in quantitative loss of bone tissue. Since stem cell-derived extracellular vesicles (EVs) are growing attention as novel cell-free therapeutics that have advantages over parental stem cells, the therapeutic effects of EVs from adipose tissue-derived stem cells (ASC-EVs) on osteoporosis pathogenesis were investigated. ASC-EVs were isolated by a multi-filtration system based on the tangential flow filtration (TFF) system and characterized using transmission electron microscopy, dynamic light scattering, zeta potential, flow cytometry, cytokine arrays, and enzyme-linked immunosorbent assay. EVs are rich in growth factors and cytokines related to bone metabolism and mesenchymal stem cell (MSC) migration. In particular, osteoprotegerin (OPG), a natural inhibitor of receptor activator of nuclear factor-κB ligand (RANKL), was highly enriched in ASC-EVs. We found that the intravenous administration of ASC-EVs attenuated bone loss in osteoporosis mice. Also, ASC-EVs significantly inhibited osteoclast differentiation of macrophages and promoted the migration of bone marrow-derived MSCs (BM-MSCs). However, OPG-depleted ASC-EVs did not show anti-osteoclastogenesis effects, demonstrating that OPG is critical for the therapeutic effects of ASC-EVs. Additionally, small RNA sequencing data were analysed to identify miRNA candidates related to anti-osteoporosis effects. miR-21-5p in ASC-EVs inhibited osteoclast differentiation through Acvr2a down-regulation. Also, let-7b-5p in ASC-EVs significantly reduced the expression of genes related to osteoclastogenesis. Finally, ASC-EVs reached the bone tissue after they were injected intravenously, and they remained longer. OPG, miR-21-5p, and let-7b-5p in ASC-EVs inhibit osteoclast differentiation and reduce gene expression related to bone resorption, suggesting that ASC-EVs are highly promising as cell-free therapeutic agents for osteoporosis treatment.

Indexed as

Adipose TissueAnimalsDisease Models, AnimalExtracellular VesiclesFemaleHumansMiceOsteoporosisOsteoprotegerinStem CellsOsteoprotegerinextracellular vesicleshuman adipose tissue-derived stem cellslet-7b-5pmiR-21-5posteoporosisosteoprotegerin

Identifiers

PMID34596354
PMCPMC8485335
OpenAlexW3202652253

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.