Evidence map›Paper›PMID 22773442›Full record

ArticleCirculation research2012

Smooth muscle cell-specific runx2 deficiency inhibits vascular calcification.

Yong Sun, Chang Hyun Byon, Kaiyu Yuan, Jianfeng Chen, Xia Mao, Jack M Heath, Amjad Javed, Kui Zhang, Peter G Anderson, Yabing Chen

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
195citing papers in PubMed, 1 pooled it
8.6field-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

195 citing papers in PubMed, 1 synthesis or guideline pooled it, 324 citations in OpenAlex.

  1. Preclinical techniques to investigate exercise training in vascular pathophysiology.American journal of physiology. Heart and circulatory physiology · 2021
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135 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

10 authors at 1 institution in 1 country.

Yong SunDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Chang Hyun Byon
Kaiyu Yuan
Jianfeng Chen
Xia Mao
Jack M Heath
Amjad Javed
Kui Zhang
Peter G Anderson
Yabing Chen
Birmingham VA Medical Center · US

Funding

Training Program in Cardiovascular PathophysiologyT32HL007918 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BALLINGER, SCOTT W. · 1999 to 2018
$3.6M
Molecular Signaling in Oxidative Stress-induced Vascular CalcificationR01HL092215 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CHEN, YABING · 2009 to 2018
$3.6M
Sp7 Mediated Control of Runx2 Function for Osteoblast DifferentiationR01AR062091 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI JAVED, AMJAD · 2012 to 2025
$3.4M
Runx2 Controlled Adipocytic Differentiation in Aging MusculoskeletonR01AG030228 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI JAVED, AMJAD · 2006 to 2009
$952k
Function of Phospholipase Cgamma2 in RANKL-Induced OsteoclastogenesisR03AR055339 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CHEN, YABING · 2008 to 2010
$217k
Toll-like receptor signaling in pathogenesis of pulmonary hypertensionI01BX000369 · VA · BIRMINGHAM VA MEDICAL CENTER · PI CHEN, YABING · 2009 to 2013
–
BLRD VA I01 BX000369NHLBI NIH HHS HL007918NHLBI NIH HHS HL092215NHLBI NIH HHS R01 HL092215NHLBI NIH HHS T32 HL007918NIAMS NIH HHS AR062091NIAMS NIH HHS R01 AR062091NIAMS NIH HHS R03 AR055339NIA NIH HHS R01 AG030228
6 · The paper itself

Abstract

rationaleVascular calcification is a hallmark of atherosclerosis, a major cause of morbidity and mortality in the United States. We have previously reported that the osteogenic transcription factor Runx2 is an essential and sufficient regulator of calcification of vascular smooth muscle cells (VSMC) in vitro.

objectiveTo determine the contribution of osteogenic differentiation of VSMC to the pathogenesis of vascular calcification and the function of VSMC-derived Runx2 in regulating calcification in vivo. METHODS AND

resultsSMC-specific Runx2-deficient mice, generated by breeding SM22α-Cre mice with the Runx2 exon 8 floxed mice, exhibited normal aortic gross anatomy and expression levels of SMC-specific marker genes. Runx2 deficiency did not affect basal SMC markers, but inhibited oxidative stress-reduced expression of SMC markers. High-fat-diet-induced vascular calcification in vivo was markedly inhibited in the Runx2-deficient mice in comparison with their control littermates. Runx2 deficiency inhibited the expression of receptor activator of nuclear factor κB ligand, which was accompanied by decreased macrophage infiltration and formation of osteoclast-like cells in the calcified lesions. Coculture of VSMC with bone marrow-derived macrophages demonstrated that the Runx2-deficient VSMC failed to promote differentiation of macrophages into osteoclast-like cells.

conclusionsThese data have determined the importance of osteogenic differentiation of VSMC in the pathogenesis of vascular calcification in mice and defined the functional role of SMC-derived Runx2 in regulating vascular calcification and promoting infiltration of macrophages into the calcified lesion to form osteoclast-like cells. Our studies suggest that the development of vascular calcification is coupled with the formation of osteoclast-like cells, paralleling the bone remodeling process.

Indexed as

Acid PhosphataseAnimalsAtherosclerosisBone RemodelingCalcinosisCell DifferentiationCells, CulturedCoculture TechniquesCore Binding Factor Alpha 1 SubunitDiet, High-FatDisease Models, AnimalExonsFemaleIsoenzymesMacrophagesMaleAcid PhosphataseCore Binding Factor Alpha 1 SubunitIsoenzymesRANK LigandRunx2 protein, mouseTartrate-Resistant Acid PhosphataseTnfsf11 protein, mouse

Identifiers

PMID22773442
PMCPMC3678289
OpenAlexW2114439420

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.