Evidence map›Paper›PMID 15841209›Full record

ArticleThe Journal of clinical investigation2005

Msx2 promotes cardiovascular calcification by activating paracrine Wnt signals.

Jian-Su Shao, Su-Li Cheng, Joyce M Pingsterhaus, Nichole Charlton-Kachigian, Arleen P Loewy, Dwight A Towler

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 224 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
224citing papers in PubMed, 1 pooled it
12.8field-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

224 citing papers in PubMed, 1 synthesis or guideline pooled it, 440 citations in OpenAlex.

  1. Pooled it
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  18. In chronic kidney disease altered cardiac metabolism precedes cardiac hypertrophy.American journal of physiology. Renal physiology · 2024
    Article
  19. Article
  20. Similarities and Differences of Vascular Calcification in Diabetes and Chronic Kidney Disease.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024
    Review

164 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

6 authors at 1 institution in 1 country.

Jian-Su ShaoDepartment of Medicine, Division of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Su-Li Cheng
Joyce M Pingsterhaus
Nichole Charlton-Kachigian
Arleen P Loewy
Dwight A Towler
Washington University in St. Louis · US

Funding

OSTEOGENIC REGULATION OF VASCULAR CALCIFICATIONR01HL069229 · NHLBI · WASHINGTON UNIVERSITY · PI TOWLER, DWIGHT A. · 2001 to 2022
$7.9M
HOXBOXES, HOMEODOMAINS, AND OSTEOBLAST GENE EXPRESSIONR01AR043731 · NIAMS · WASHINGTON UNIVERSITY · PI TOWLER, DWIGHT A. · 1996 to 2007
$1.6M
MINERAL AND SKELETAL METABOLISMT32AR007033 · NIAMS · WASHINGTON UNIVERSITY · PI TOWLER, DWIGHT A · 1986 to 2004
$1.0M
NHLBI NIH HHS HL69229NHLBI NIH HHS R01 HL069229NIAMS NIH HHS AR07033NIAMS NIH HHS AR43731NIAMS NIH HHS R01 AR043731NIAMS NIH HHS T32 AR007033
6 · The paper itself

Abstract

In diabetic LDLR-/- mice, an ectopic BMP2-Msx2 gene regulatory program is upregulated in association with vascular calcification. We verified the procalcific actions of aortic Msx2 expression in vivo. CMV-Msx2 transgenic (CMV-Msx2Tg(+)) mice expressed 3-fold higher levels of aortic Msx2 than nontransgenic littermates. On high-fat diets, CMV-Msx2Tg(+) mice exhibited marked cardiovascular calcification involving aortic and coronary tunica media. This corresponded to regions of Msx2 immunoreactivity in adjacent adventitial myofibroblasts, suggesting a potential paracrine osteogenic signal. To better understand Msx2-regulated calcification, we studied actions in 10T1/2 cells. We found that conditioned media from Msx2-transduced 10T1/2 cells (Msx2-CM) is both pro-osteogenic and adipostatic; these features are characteristic of Wnt signaling. Msx2-CM stimulated Wnt-dependent TCF/LEF transcription, and Msx2-transduced cells exhibited increased nuclear beta-catenin localization with concomitant alkaline phosphatase induction. Msx2 upregulated Wnt3a and Wnt7a but downregulated expression of the canonical inhibitor Dkk1. Dkk1 treatment reversed osteogenic and adipostatic actions of Msx2. Teriparatide, a PTH1R agonist that inhibits murine vascular calcification, suppressed vascular BMP2-Msx2-Wnt signaling. Analyses of CMV-Msx2Tg(+) mice confirmed that Msx2 suppresses aortic Dkk1 and upregulates vascular Wnts; moreover, TOPGAL(+) (Wnt reporter); CMV-Msx2Tg(+) mice exhibited augmented aortic LacZ expression. Thus, Msx2-expressing cells elaborated an osteogenic milieu that promotes vascular calcification in part via paracrine Wnt signals.

Indexed as

Alkaline PhosphataseAnimalsbeta CateninCalcinosisCardiovascular SystemCulture Media, ConditionedCytomegalovirusCytoskeletal ProteinsDNA-Binding ProteinsGenetic VectorsHomeodomain ProteinsIntercellular Signaling Peptides and ProteinsLipid MetabolismMiceMice, TransgenicParacrine CommunicationAlkaline Phosphatasebeta CateninCTNNB1 protein, mouseCulture Media, ConditionedCytoskeletal ProteinsDNA-Binding ProteinsHomeodomain ProteinsIntercellular Signaling Peptides and ProteinsMSX2 proteinTrans-ActivatorsWnt Proteins

Identifiers

PMID15841209
PMCPMC1077175
OpenAlexW2051580972

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.