Evidence map›Paper›PMID 25711193›Full record

ArticleJournal of cellular biochemistry2015

Smad1/5 and Smad4 expression are important for osteoclast differentiation.

Amy Tasca, Melissa Stemig, Aaron Broege, Brandon Huang, Julia Davydova, An Zwijsen, Lieve Umans, Eric D Jensen, Raj Gopalakrishnan, Kim C Mansky

Abstract read
In one paragraph

Article in Journal of cellular biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

18 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
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  11. The Bone Morphogenetic Protein Pathway: The Osteoclastic Perspective.Frontiers in cell and developmental biology · 2020
    Review
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  15. Article
  16. Pharmacologic Calcitriol Inhibits Osteoclast Lineage Commitment via the BMP-Smad1 and IκB-NF-κB Pathways.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2017
    Article
  17. Article
  18. Review
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 4 institutions in 2 countries.

Amy TascaDepartment of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota, 55455.
Melissa StemigDepartment of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota, 55455.
Aaron BroegeDepartment of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota, 55455.
Brandon HuangDepartment of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, Minnesota, 55455.
Julia DavydovaDepartment of Surgery, University of Minnesota Medical School, Minneapolis, Minnesota, 55455.
An ZwijsenVIB Center for the Biology of Disease, VIB, KU Leuven Department of Human Genetics, Leuven, 3000, Belgium.
Lieve UmansStem Cell Biology and Embryology, KU Leuven, Leuven, 3000, Belgium.
Eric D JensenDepartment of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota, 55455.
Raj GopalakrishnanDepartment of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota, 55455.
Kim C ManskyDepartment of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, Minnesota, 55455.
University of Minnesota · USKU Leuven · BEUniversity of Minnesota Medical Center · USVIB-KU Leuven Center for Cancer Biology · BE

Funding

Minnesota Craniofacial Research Training ProgramT90DE022732 · NIDCR · UNIVERSITY OF MINNESOTA · PI MANSKY, KIM CARPENTER · 2012 to 2023
$4.9M
Role of HDAC7 in Osteoclast DifferentiationR01AR061352 · NIAMS · UNIVERSITY OF MINNESOTA · PI JENSEN, ERIC D, MANSKY, KIM CARPENTER · 2013 to 2017
$1.8M
Role of Twisted Gastrulation in OsteoclastogenesisR01AR056642 · NIAMS · UNIVERSITY OF MINNESOTA · PI GOPALAKRISHNAN, RAJARAM · 2010 to 2014
$1.6M
The role of MyosinX in BMPs promotion of SMAD 1/5 in osteoclast formation and funF32DE024679 · NIDCR · UNIVERSITY OF MINNESOTA · PI TASCA, AMY · 2014 to 2015
$138k
NIAMS NIH HHS AR056642NIAMS NIH HHS AR 061352NIAMS NIH HHS R01 AR056642NIAMS NIH HHS R01 AR061352NIDCR NIH HHS F32 DE024679NIDCR NIH HHS T90 DE022732
6 · The paper itself

Abstract

To investigate the necessity of the canonical BMP pathway during osteoclast differentiation, we created osteoclasts with a conditional gene deletion for Smad1 and Smad5 (SMAD1/5), or Smad4 using adenovirus expressing CRE recombinase (Ad-CRE). Reduction of either Smad4 or Smad1/5 expression resulted in fewer and smaller multinuclear cells compared to control cells. We also detected changes in osteoclast enriched genes, demonstrated by decreased Dc-stamp and cathepsin K expression in both Smad4 and Smad1/5 Ad-CRE osteoclasts, and changes in c-fos and Nfatc1 expression in only Smad4 Ad-CRE cells. Lastly we also detected a significant decrease in resorption pits and area resorbed in both the Smad4 and Smad1/5 Ad-CRE osteoclasts. Because we inhibited osteoclast differentiation with loss of either Smad4 or Smad1/5 expression, we assessed whether BMPs affected osteoclast activity in addition to BMP's effects on differentiation. Therefore, we treated mature osteoclasts with BMP2 or with dorsomorphin, a chemical inhibitor that selectively suppresses canonical BMP signaling. We demonstrated that BMP2 stimulated resorption in mature osteoclasts whereas treatment with dorsomorphin blocks osteoclast resorption. These results indicate that the BMP canonical signaling pathway is important for osteoclast differentiation and activity.

Indexed as

AnimalsBone Marrow CellsBone Morphogenetic Protein 2Bone Morphogenetic ProteinsCell DifferentiationGene DeletionGene Expression RegulationMiceOsteoclastsPyrazolesPyrimidinesSignal TransductionSmad1 ProteinSmad4 ProteinSmad5 ProteinBone Morphogenetic Protein 2Bone Morphogenetic ProteinsdorsomorphinPyrazolesPyrimidinesSmad1 ProteinSmad1 protein, mouseSmad4 ProteinSmad4 protein, mouseSmad5 ProteinSmad5 protein, mouseBMPsFUSIONOSTEOCLASTSRESORPTIONSMADsTGF-β

Identifiers

PMID25711193
PMCPMC4431909
OpenAlexW2133455379

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.