Evidence map›Paper›PMID 27741240›Full record

ArticlePLoS genetics2016

Smad2 and Smad3 Regulate Chondrocyte Proliferation and Differentiation in the Growth Plate.

Weiguang Wang, Buer Song, Teni Anbarchian, Anna Shirazyan, Joshua E Sadik, Karen M Lyons

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

41 citing papers in PubMed, 58 citations in OpenAlex.

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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.

Weiguang WangDepartment of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
Buer SongDepartment of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
Teni AnbarchianDepartment of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
Anna ShirazyanDepartment of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
Joshua E SadikDepartment of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.ORCID http://orcid.org/0000-0002-9371-893X
Karen M LyonsDepartment of Orthopaedic Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.ORCID http://orcid.org/0000-0001-9420-5813
University of California, Los Angeles · US

Funding

UCLA MSD ProgramR25GM055052 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BARBER, PAUL HENRY, HASSON, TAMA W. · 1996 to 2021
$9.2M
BMPS IN SKELETAL GROWTH AND OSTEOGENIC DIFFERENTIATIONR01AR044528 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LYONS, KAREN M. · 1998 to 2017
$5.2M
Regenerative Musculoskeletal Medicine Training ProgramT32AR059033 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI John S Adams, Nicholas M. Bernthal · 2011 to 2026
$4.8M
NIAMS NIH HHS R01 AR044528NIAMS NIH HHS T32 AR059033NIGMS NIH HHS R25 GM055052
6 · The paper itself

Abstract

TGFβs act through canonical and non-canonical pathways, and canonical signals are transduced via Smad2 and Smad3. However, the contribution of canonical vs. non-canonical pathways in cartilage is unknown because the role of Smad2 in chondrogenesis has not been investigated in vivo. Therefore, we analyzed mice in which Smad2 is deleted in cartilage (Smad2CKO), global Smad3-/- mutants, and crosses of these strains. Growth plates at birth from all mutant strains exhibited expanded columnar and hypertrophic zones, linked to increased proliferation in resting chondrocytes. Defects were more severe in Smad2CKO and Smad2CKO;Smad3-/- (Smad2/3) mutant mice than in Smad3-/- mice, demonstrating that Smad2 plays a role in chondrogenesis. Increased levels of Ihh RNA, a key regulator of chondrocyte proliferation and differentiation, were seen in prehypertrophic chondrocytes in the three mutant strains at birth. In accordance, TGFβ treatment decreased Ihh RNA levels in primary chondrocytes from control (Smad2fx/fx) mice, but inhibition was impaired in cells from mutants. Consistent with the skeletal phenotype, the impact on TGFβ-mediated inhibition of Ihh RNA expression was more severe in Smad2CKO than in Smad3-/- cells. Putative Smad2/3 binding elements (SBEs) were identified in the proximal Ihh promoter. Mutagenesis demonstrated a role for three of them. ChIP analysis suggested that Smad2 and Smad3 have different affinities for these SBEs, and that the repressors SnoN and Ski were differentially recruited by Smad2 and Smad3, respectively. Furthermore, nuclear localization of the repressor Hdac4 was decreased in growth plates of Smad2CKO and double mutant mice. TGFβ induced association of Hdac4 with Smad2, but not with Smad3, on the Ihh promoter. Overall, these studies revealed that Smad2 plays an essential role in the development of the growth plate, that both Smads 2 and 3 inhibit Ihh expression in the neonatal growth plate, and suggested they accomplish this by binding to distinct SBEs, mediating assembly of distinct repressive complexes.

Indexed as

AnimalsCartilageCell DifferentiationCell ProliferationChondrocytesChondrogenesisGene Expression Regulation, DevelopmentalGrowth PlateHedgehog ProteinsHistone DeacetylasesMicePromoter Regions, GeneticSmad2 ProteinSmad3 ProteinTransforming Growth Factor betaHdac5 protein, mouseHedgehog ProteinsHistone Deacetylasesihh protein, mouseSmad2 ProteinSmad2 protein, mouseSmad3 ProteinSmad3 protein, mouseTransforming Growth Factor beta

Identifiers

PMID27741240
PMCPMC5065210
OpenAlexW2530671957

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.