Evidence map›Paper›PMID 26555637›Full record

ArticleBone2016

CCN4/WISP-1 positively regulates chondrogenesis by controlling TGF-β3 function.

Yuya Yoshioka, Mitsuaki Ono, Azusa Maeda, Tina M Kilts, Emilio Satoshi Hara, Hany Khattab, Junji Ueda, Eriko Aoyama, Toshitaka Oohashi, Masaharu Takigawa and 2 more

Open access · greenAbstract read
In one paragraph

Article in Bone, 2016. 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
1.1field-weighted citation impact, top 23% 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, 34 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

12 authors at 2 institutions in 2 countries.

Yuya YoshiokaDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Mitsuaki OnoDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address: mitsuaki@md.okayama-u.ac.jp.
Azusa MaedaDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Tina M KiltsCraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Emilio Satoshi HaraDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Hany KhattabDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Advanced Research Center for Oral & Craniofacial Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Junji UedaDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Eriko AoyamaAdvanced Research Center for Oral & Craniofacial Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Toshitaka OohashiAdvanced Research Center for Oral & Craniofacial Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Masaharu TakigawaAdvanced Research Center for Oral & Craniofacial Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Marian F YoungCraniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Takuo KubokiDepartment of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Okayama University · JPNational Institute of Dental and Craniofacial Research · US

Funding

Function Of Skeletal Matrix GenesZIADE000379 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI YOUNG, MARIAN F · 2009 to 2023
$23.6M
STRUCTURE AND BONE MATRIX GENE EXPRESSIONZ01DE000379 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI YOUNG, MARIAN F · 1985 to 2008
$2.5M
Intramural NIH HHS Z01 DE000379
6 · The paper itself

Abstract

The CCN family of proteins plays important roles in development and homeostasis of bone and cartilage. To understand the role of CCN4 in chondrogenesis, human bone marrow stromal cells (hBMSCs) were transduced with CCN4 adenovirus (adCCN4) or siRNA to CCN4 (siCCN4) in the presence or absence of transforming growth factor-β3 (TGF-β3). Overexpression of CCN4 enhanced TGF-β3-induced SMAD2/3 phosphorylation and chondrogenesis of hBMSCs in an in vitro assay using a micromass culture model. On the other hand, knockdown of CCN4 inhibited the TGF-β3-induced SMAD2/3 phosphorylation and synthesis of cartilage matrix in micromass cultures of hBMSCs. Immunoprecipitation-western blot analysis revealed that CCN4 bound to TGF-β3 and regulated the ability of TGF-β3 to bind to hBMSCs. In vivo analysis confirmed there was a significant decrease in the gene expression levels of chondrocyte markers in cartilage samples from Ccn4-knock out (KO) mice, compared to those from wild type (WT) control. In order to investigate the regenerative properties of the articular cartilage in Ccn4-KO mice, articular cartilage defects were surgically performed in the knee joints of young mice, and the results showed that the cartilage was partially repaired in WT mice, but not in Ccn4-KO mice. In conclusion, these results show, for the first time, that CCN4 has a positive influence on chondrogenic differentiation by modulating the effects of TGF-β3.

Indexed as

ChondrogenesisAnimalsBiomarkersCartilage, ArticularCCN Intercellular Signaling ProteinsCell DifferentiationCells, CulturedGene Expression RegulationHumansMesenchymal Stem CellsMice, KnockoutPhosphorylationProtein BindingProto-Oncogene ProteinsReal-Time Polymerase Chain ReactionRegenerationBiomarkersCCN4 protein, humanCCN4 protein, mouseCCN Intercellular Signaling ProteinsProto-Oncogene ProteinsSmad ProteinsTransforming Growth Factor beta3Articular cartilageBone marrow stromal cell (BMSC)CCN4/WISP-1ChondrogenesisTGF-β3

Identifiers

PMID26555637
PMCPMC5749225
OpenAlexW2136216177

What OpenQuestion holds

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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.