Evidence map›Paper›PMID 26307668›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016

Suppression of EZH2 Prevents the Shift of Osteoporotic MSC Fate to Adipocyte and Enhances Bone Formation During Osteoporosis.

Huan Jing, Li Liao, Yulin An, Xiaoxia Su, Shiyu Liu, Yi Shuai, Xinjing Zhang, Yan Jin

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

107 citing papers in PubMed, 157 citations in OpenAlex.

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  8. eLife · 2025
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  10. bioRxiv : the preprint server for biology · 2025
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  17. Genetic and Epigenetic Interactions Involved in Senescence of Stem Cells.International journal of molecular sciences · 2024
    Review
  18. Review
  19. Article
  20. Review

47 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

8 authors at 3 institutions in 1 country.

Huan JingState Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China; Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China; State Key Laboratory of Military Stomatology, Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China.
Li LiaoState Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China; Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China; State Key Laboratory of Military Stomatology, Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China.
Yulin AnState Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China; Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China; State Key Laboratory of Military Stomatology, Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China; Zhenjiang Entry-Exit Inspection And Quarantine Bureau, Jiangsu, China.
Xiaoxia SuDepartment of Orthodontics, Stomatology Hospital of Xi'an Jiaotong University College of Medicine, Shaanxi, China.
Shiyu LiuState Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China; Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China; State Key Laboratory of Military Stomatology, Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China.
Yi ShuaiState Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China; Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China; State Key Laboratory of Military Stomatology, Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China.
Xinjing ZhangDepartment of Prothodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, China.
Yan JinState Key Laboratory of Military Stomatology, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, China; Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: yanjin@fmmu.edu.cn.
Air Force Medical University · CNStomatological Hospital of Chongqing Medical University · CNStomatology Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

During osteoporosis, the shift of mesenchymal stem cell (MSC) lineage commitment to adipocyte leads to the imbalance between bone mass and fat, which increases the risk of fracture. The Enhancer of Zeste homology 2 (EZH2), which methylates histone H3 on lysine 27 (H3K27me3), controls MSC cell lineage commitment. However, whether EZH2 is related to osteoporosis remains elusive. In our study, we found EZH2 expression was significantly increased in osteoporotic MSCs. EZH2 directly increased H3K27me3 levels on promoters of Wnt1, Wnt6, and Wnt10a to silence Wnt gene transcription. The inhibition of Wnt/β-catenin signaling shifted MSC cell lineage commitment to adipocyte. Knockdown of EZH2 by lentivirus-expressing shRNA rescued the abnormal fate of osteoporotic MSC. By employing the H3K27me3 inhibitor DZNep, we effectively derepressed Wnt signaling and improved osteogenic differentiation of osteoporotic MSCs in vitro. Furthermore, in vivo administration of DZNep successfully increased bone formation and repressed excessive bone marrow fat formation in osteoporotic mice. Noteworthy, DZNep treatment persistently enhanced osteogenic differentiation of endogenous MSCs. In conclusion, our study demonstrated that redundant EZH2 shifted MSC cell lineage commitment to adipocyte, which contributed to the development of osteoporosis. We also provided EZH2 as a novel therapeutic target for improving bone formation during osteoporosis.

Indexed as

OsteogenesisAdipocytesAnimalsCell DifferentiationDisease Models, AnimalDNA MethylationEnhancer of Zeste Homolog 2 ProteinFemaleGene Knockdown TechniquesHistonesMesenchymal Stem CellsMiceOsteoporosisPolycomb Repressive Complex 2Wnt ProteinsEnhancer of Zeste Homolog 2 ProteinEzh2 protein, mouseHistonesPolycomb Repressive Complex 2Wnt Proteins

Identifiers

PMID26307668
PMCPMC4817806
OpenAlexW1144202826

What OpenQuestion holds

Textmetadata
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.