Evidence map›Paper›PMID 24840563›Full record

ArticlePloS one2014

Influence of ARHGEF3 and RHOA knockdown on ACTA2 and other genes in osteoblasts and osteoclasts.

Benjamin H Mullin, Cyril Mamotte, Richard L Prince, Scott G Wilson

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
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, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Role of ARHGEF3 as a GEF and mTORC2 Regulator.Frontiers in cell and developmental biology · 2021
    Review
  8. Article
  9. Article
  10. Article
  11. The double edge sword of fibrosis in cancer.Translational research : the journal of laboratory and clinical medicine · 2019
    Review
  12. Article
  13. Article
  14. RhoA knockout fibroblasts lose tumor-inhibitory capacity in vitro and promote tumor growth in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  15. Article
  16. Article
  17. Article
  18. Article
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

4 authors at 3 institutions in 2 countries.

Benjamin H MullinDept. of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; School of Biomedical Sciences and CHIRI Biosciences Research Precinct, Faculty of Health Sciences, Curtin University, Bentley, Western Australia, Australia; School of Medicine and Pharmacology, The University of Western Australia, Nedlands, Western Australia, Australia.
Cyril MamotteSchool of Biomedical Sciences and CHIRI Biosciences Research Precinct, Faculty of Health Sciences, Curtin University, Bentley, Western Australia, Australia.
Richard L PrinceDept. of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; School of Medicine and Pharmacology, The University of Western Australia, Nedlands, Western Australia, Australia.
Scott G WilsonDept. of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia; School of Medicine and Pharmacology, The University of Western Australia, Nedlands, Western Australia, Australia; Twin and Genetic Epidemiology Research Unit, St Thomas' Hospital Campus, King's College London, London, United Kingdom.
Curtin University · AUSt Thomas' Hospital · GBUniversity of Western Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteoporosis is a common bone disease that has a strong genetic component. Genome-wide linkage studies have identified the chromosomal region 3p14-p22 as a quantitative trait locus for bone mineral density (BMD). We have previously identified associations between variation in two related genes located in 3p14-p22, ARHGEF3 and RHOA, and BMD in women. In this study we performed knockdown of these genes using small interfering RNA (siRNA) in human osteoblast-like and osteoclast-like cells in culture, with subsequent microarray analysis to identify genes differentially regulated from a list of 264 candidate genes. Validation of selected findings was then carried out in additional human cell lines/cultures using quantitative real-time PCR (qRT-PCR). The qRT-PCR results showed significant down-regulation of the ACTA2 gene, encoding the cytoskeletal protein alpha 2 actin, in response to RHOA knockdown in both osteoblast-like (P<0.001) and osteoclast-like cells (P = 0.002). RHOA knockdown also caused up-regulation of the PTH1R gene, encoding the parathyroid hormone 1 receptor, in Saos-2 osteoblast-like cells (P<0.001). Other findings included down-regulation of the TNFRSF11B gene, encoding osteoprotegerin, in response to ARHGEF3 knockdown in the Saos-2 and hFOB 1.19 osteoblast-like cells (P = 0.003-0.02), and down-regulation of ARHGDIA, encoding the Rho GDP dissociation inhibitor alpha, in response to RHOA knockdown in osteoclast-like cells (P<0.001). These studies identify ARHGEF3 and RHOA as potential regulators of a number of genes in bone cells, including TNFRSF11B, ARHGDIA, PTH1R and ACTA2, with influences on the latter evident in both osteoblast-like and osteoclast-like cells. This adds further evidence to previous studies suggesting a role for the ARHGEF3 and RHOA genes in bone metabolism.

Indexed as

ActinsBone DensityChromosomes, Human, Pair 3FemaleGene Expression RegulationGene Knockdown TechniquesHumansMicroarray AnalysisOsteoblastsOsteoclastsOsteoporosisReal-Time Polymerase Chain ReactionReceptor, Parathyroid Hormone, Type 1rhoA GTP-Binding ProteinRho Guanine Nucleotide Exchange FactorsRNA, Small InterferingACTA2 protein, humanActinsARHGEF3 protein, humanPTH1R protein, humanReceptor, Parathyroid Hormone, Type 1rhoA GTP-Binding ProteinRHOA protein, humanRho Guanine Nucleotide Exchange FactorsRNA, Small Interfering

Identifiers

PMID24840563
PMCPMC4026532
OpenAlexW2053478348

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.