Evidence map›Paper›PMID 21351149›Full record

ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2011

Effects of miR-335-5p in modulating osteogenic differentiation by specifically downregulating Wnt antagonist DKK1.

Jin Zhang, Qisheng Tu, Lynda F Bonewald, Xi He, Gary Stein, Jane Lian, Jake Chen

Abstract read
In one paragraph

Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers.

0numbers the graph read from it
0cells of the map it votes in
157citing papers in PubMed
8.0field-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

157 citing papers in PubMed, 286 citations in OpenAlex.

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97 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 5 institutions in 2 countries.

Jin ZhangDivision of Oral Biology, Tufts University School of Dental Medicine, Boston, MA 02111, USA.
Qisheng Tu
Lynda F Bonewald
Xi He
Gary Stein
Jane Lian
Jake Chen
Tufts University · USUniversity of Massachusetts Chan Medical School · USHarvard University · USShandong University · CNUniversity of Missouri–Kansas City · US

Funding

Transgenic CoreP01AR046798 · NIAMS · UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANT · PI BONEWALD, LYNDA F · 2001 to 2010
$10.5M
CONTROL OF OSTEOBLAST PROLIFERATION AND DIFFERENTIATIONR01AR039588 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LIAN, JANE B., STEIN, GARY S. · 1990 to 2019
$8.0M
Wnt-LRP interaction in Wnt signal transductionR01GM057603 · NIGMS · CHILDREN'S HOSPITAL BOSTON · PI HE, XI · 1999 to 2018
$6.3M
Synthesis of Osteocalcin in BoneR37DE012528 · NIDCR · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI LIAN, JANE B. · 2008 to 2017
$5.0M
Genetic and Chemical Biological Studies of a Novel Wnt Inhibitor Tiki2R01AR060359 · NIAMS · BOSTON CHILDREN'S HOSPITAL · PI HE, XI · 2011 to 2015
$2.8M
Bone Marrow Stromal Cells in Oral and Craniofacial Tissue RegenerationR01DE016710 · NIDCR · TUFTS UNIVERSITY BOSTON · PI CHEN, JAKE JINKUN · 2007 to 2010
$1.4M
Cell Differentiation in Periodontal RegenerationR01DE014537 · NIDCR · TUFTS UNIVERSITY BOSTON · PI CHEN, JAKE JINKUN · 2003 to 2006
$1.3M
Therapeutic Strategies for Treating Type 2 Diabetes Mellitus -Associated PeriodonR01DE021464 · NIDCR · TUFTS UNIVERSITY BOSTON · PI CHEN, JAKE JINKUN · 2011 to 2013
$1.3M
MECHANISM OF WNT SIGNAL TRANSDUCTIONR55GM057603 · NIGMS · CHILDREN'S HOSPITAL BOSTON · PI HE, XI · 1998 to 1998
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NIAMS NIH HHS AR039588NIAMS NIH HHS P01 AR046798NIAMS NIH HHS P01-AR46798NIAMS NIH HHS R01 AR039588NIAMS NIH HHS R01 AR060359NIDCR NIH HHS DE14537NIDCR NIH HHS DE16710NIDCR NIH HHS R01 DE014537NIDCR NIH HHS R01 DE016710NIDCR NIH HHS R01 DE021464NIDCR NIH HHS R37 DE012528NIGMS NIH HHS GM57603NIGMS NIH HHS R01 GM057603
6 · The paper itself

Abstract

Dickkopf-related protein 1 (DKK1) is essential to maintain skeletal homeostasis as an inhibitor of Wnt signaling and osteogenic differentiation. The purpose of this study was to investigate the molecular mechanisms underlying the developmental stage-specific regulation of the DKK1 protein level. We performed a series of studies including luciferase reporter assays, micro-RNA microarray, site-specific mutations, and gain- and loss-of-function analyses. We found that the DKK1 protein level was regulated via DKK1 3' UTR by miRNA control, which was restricted to osteoblast-lineage cells. As a result of decreased DKK1 protein level by miR-335-5p, Wnt signaling was enhanced, as indicated by elevated GSK-3β phosphorylation and increased β-catenin transcriptional activity. The effects of miR-335-5p were reversed by anti-miR-335-5p treatment, which downregulated endogenous miR-335-5p. In vivo studies showed high expression levels of miR-335-5p in osteoblasts and hypertrophic chondrocytes of mouse embryos, indicating a pivotal role of miR-335-5p in regulating bone development. In conclusion, miR-335-5p activates Wnt signaling and promotes osteogenic differentiation by downregulating DKK1. This cell- and development-specific regulation is essential and mandatory for the initiation and progression of osteogenic differentiation. miR-335-5p proves to be a potential and useful targeting molecule for promoting bone formation and regeneration.

Indexed as

3' Untranslated RegionsAnimalsCell DifferentiationCell LineDown-RegulationEmbryo, MammalianGene Expression ProfilingGene Expression Regulation, DevelopmentalIntercellular Signaling Peptides and ProteinsMiceMicroRNAsOligonucleotide Array Sequence AnalysisOsteoblastsOsteogenesisReverse Transcriptase Polymerase Chain ReactionSignal Transduction3' Untranslated RegionsDkk1 protein, mouseIntercellular Signaling Peptides and ProteinsMicroRNAsMirn335 microRNA, mouseWnt Proteins

Identifiers

PMID21351149
PMCPMC3810406
OpenAlexW2095004208

What OpenQuestion holds

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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.