Evidence map›Paper›PMID 24340027›Full record

ArticlePloS one2013

Crosstalk between Wnt/β-catenin and estrogen receptor signaling synergistically promotes osteogenic differentiation of mesenchymal progenitor cells.

Yanhong Gao, Enyi Huang, Hongmei Zhang, Jinhua Wang, Ningning Wu, Xian Chen, Ning Wang, Sheng Wen, Guoxin Nan, Fang Deng and 8 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

78 citing papers in PubMed, 113 citations in OpenAlex.

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  6. Effect of romosozumab on bone mineral density and trabecular bone score in premenopausal women with low bone mass.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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  15. A mixture ofHeliyon · 2024
    Article
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18 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

18 authors at 7 institutions in 2 countries.

Yanhong GaoDepartment of Geriatrics, Xinhua Hospital of Shanghai Jiaotong University, School of Medicine, Shanghai, China ; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, Illinois, United States of America.
Enyi Huang
Hongmei Zhang
Jinhua Wang
Ningning Wu
Xian Chen
Ning Wang
Sheng Wen
Guoxin Nan
Fang Deng
Zhan Liao
Di Wu
Bosi Zhang
Junhui Zhang
Rex C Haydon
Hue H Luu
Lewis L Shi
Tong-Chuan He
University of Chicago Medical Center · USChongqing Medical University · CNMolecular Oncology (United States) · USStomatological Hospital of Chongqing Medical University · CNArmy Medical University · CNCentral South University · CNXinHua Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteogenic differentiation from mesenchymal progenitor cells (MPCs) are initiated and regulated by a cascade of signaling events. Either Wnt/β-catenin or estrogen signaling pathway has been shown to play an important role in regulating skeletal development and maintaining adult tissue homeostasis. Here, we investigate the potential crosstalk and synergy of these two signaling pathways in regulating osteogenic differentiation of MPCs. We find that the activation of estrogen receptor (ER) signaling by estradiol (E2) or exogenously expressed ERα in MPCs synergistically enhances Wnt3A-induced early and late osteogenic markers, as well as matrix mineralization. The E2 or ERα-mediated synergy can be effectively blocked by ERα antagonist tamoxifen. E2 stimulation can enhance endochondral ossification of Wnt3A-transduced mouse fetal limb explants. Furthermore, exogenously expressed ERα significantly enhances the maturity and mineralization of Wnt3A-induced subcutaneous and intramuscular ectopic bone formation. Mechanistically, we demonstrate that E2 does not exert any detectable effect on β-catenin/Tcf reporter activity. However, ERα expression is up-regulated within the first 48h in AdWnt3A-transduced MPCs, whereas ERβ expression is significantly inhibited within 24h. Moreover, the key enzyme for the biosynthesis of estrogens aromatase is modulated by Wnt3A in a biphasic manner, up-regulated at 24h but reduced after 48h. Our results demonstrate that, while ER signaling acts synergistically with Wnt3A in promoting osteogenic differentiation, Wnt3A may crosstalk with ER signaling by up-regulating ERα expression and down-regulating ERβ expression in MPCs. Thus, the signaling crosstalk and synergy between these two pathways should be further explored as a potential therapeutic approach to combating bone and skeletal disorders, such as fracture healing and osteoporosis.

Indexed as

Animalsbeta CateninCell DifferentiationEstradiolEstrogen Receptor alphaEstrogen Receptor betaEstrogensHEK293 CellsHumansMesenchymal Stem CellsMiceOsteogenesisWnt3A ProteinWnt Signaling Pathwaybeta CateninESR1 protein, humanEstradiolEstrogen Receptor alphaEstrogen Receptor betaEstrogensWnt3A ProteinWNT3A protein, humanWnt3a protein, mouse

Identifiers

PMID24340027
PMCPMC3855436
OpenAlexW1980666946

What OpenQuestion holds

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LicenceCC BY
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.