Evidence map›Paper›PMID 23032104›Full record

ArticleBone2013

Wnt/β-catenin signaling activates bone morphogenetic protein 2 expression in osteoblasts.

Rongrong Zhang, Babatunde O Oyajobi, Stephen E Harris, Di Chen, Christopher Tsao, Hong-Wen Deng, Ming Zhao

Abstract read
In one paragraph

Article in Bone, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
155citing papers in PubMed, 1 pooled it
8.3field-weighted citation impact, top 2% 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

155 citing papers in PubMed, 1 synthesis or guideline pooled it, 304 citations in OpenAlex.

  1. Pooled it
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  16. CFTR mutation is associated with bone differentiation abnormalities in cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2025
    Article
  17. Review
  18. Article
  19. Article
  20. Article

95 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

7 authors at 4 institutions in 1 country.

Rongrong ZhangDepartment of Biostatistics and Bioinformatics, Tulane University, New Orleans, LA 70112, USA.
Babatunde O Oyajobi
Stephen E Harris
Di Chen
Christopher Tsao
Hong-Wen Deng
Ming Zhao
Tulane University · USThe University of Texas Health Science Center at San Antonio · USRush University · USThe University of Texas at San Antonio · US

Funding

ROBUST AND POWERFUL TEST OF CANDIDATE GENES TO BONE MASSR01AR050496 · NIAMS · UNIVERSITY OF MISSOURI KANSAS CITY · PI DENG, HONG-WEN · 2004 to 2013
$3.8M
The Mechanism through which TGF-Beta Maintains Chondrocytes in Proliferating StagR01AR054465 · NIAMS · UNIVERSITY OF ROCHESTER · PI CHEN, DI · 2007 to 2018
$2.7M
Identification of Proteins Important for Male OsteoporosisR01AR057049 · NIAMS · UNIVERSITY OF MISSOURI KANSAS CITY · PI DENG, HONG-WEN · 2009 to 2013
$2.4M
Beta-Catenin Signaling and Pathogenesis of OsteoarthritisR01AR055915 · NIAMS · UNIVERSITY OF ROCHESTER · PI CHEN, DI · 2009 to 2013
$1.7M
NIAMS NIH HHS R01 AR050496NIAMS NIH HHS R01 AR054465NIAMS NIH HHS R01 AR055915NIAMS NIH HHS R01 AR057049
6 · The paper itself

Abstract

The BMP and Wnt/β-catenin signaling pathways cooperatively regulate osteoblast differentiation and bone formation. Although BMP signaling regulates gene expression of the Wnt pathway, much less is known about whether Wnt signaling modulates BMP expression in osteoblasts. Given the presence of putative Tcf/Lef response elements that bind β-catenin/TCF transcription complex in the BMP2 promoter, we hypothesized that the Wnt/β-catenin pathway stimulates BMP2 expression in osteogenic cells. In this study, we showed that Wnt/β-catenin signaling is active in various osteoblast or osteoblast precursor cell lines, including MC3T3-E1, 2T3, C2C12, and C3H10T1/2 cells. Furthermore, crosstalk between the BMP and Wnt pathways affected BMP signaling activity, osteoblast differentiation, and bone formation, suggesting Wnt signaling is an upstream regulator of BMP signaling. Activation of Wnt signaling by Wnt3a or overexpression of β-catenin/TCF4 both stimulated BMP2 transcription at promoter and mRNA levels. In contrast, transcription of BMP2 in osteogenic cells was decreased by either blocking the Wnt pathway with DKK1 and sFRP4, or inhibiting β-catenin/TCF4 activity with FWD1/β-TrCP, ICAT, or ΔTCF4. Using a site-directed mutagenesis approach, we confirmed that Wnt/β-catenin transactivation of BMP2 transcription is directly mediated through the Tcf/Lef response elements in the BMP2 promoter. These results, which demonstrate that the Wnt/β-catenin signaling pathway is an upstream activator of BMP2 expression in osteoblasts, provide novel insights into the nature of functional cross talk integrating the BMP and Wnt/β-catenin pathways in osteoblastic differentiation and maintenance of skeletal homeostasis.

Indexed as

Signal TransductionAnimalsBase Sequencebeta CateninBone Morphogenetic Protein 2Cell LineCells, CulturedDNA PrimersMiceOsteoblastsReal-Time Polymerase Chain ReactionWnt Proteinsbeta CateninBone Morphogenetic Protein 2DNA PrimersWnt Proteins

Identifiers

PMID23032104
PMCPMC3712130
OpenAlexW2025059729

What OpenQuestion holds

Textmetadata
LicenceTDM
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.