Evidence map›Paper›PMID 30193893›Full record

ArticleMatrix biology : journal of the International Society for Matrix Biology2019

miR-324-5p is up regulated in end-stage osteoarthritis and regulates Indian Hedgehog signalling by differing mechanisms in human and mouse.

Steven Woods, Matt J Barter, Hannah R Elliott, Catherine M McGillivray, Mark A Birch, Ian M Clark, David A Young

Open access · hybridAbstract read
In one paragraph

Article in Matrix biology : journal of the International Society for Matrix Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

23 citing papers in PubMed, 42 citations in OpenAlex.

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  16. Crosstalk Among circRNA/lncRNA, miRNA, and mRNA in Osteoarthritis.Frontiers in cell and developmental biology · 2021
    Review
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  19. [The regulatory role of microRNA in osteogenic differentiation of mesenchymal stem cells and its application as a therapeutic target and diagnostic tool in orthopedic diseases].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2020
    Article
  20. 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

7 authors at 5 institutions in 1 country.

Steven WoodsDivision of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Matt J BarterSkeletal Research Group, Institute of Genetic Medicine, Central Parkway, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
Hannah R ElliottMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, BS8 2BN, UK and Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, BS8 2BN, UK.
Catherine M McGillivraySkeletal Research Group, Institute of Genetic Medicine, Central Parkway, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
Mark A BirchDivision of Trauma and Orthopaedic Surgery, University of Cambridge, Box 180, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
Ian M ClarkSchool of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
David A YoungSkeletal Research Group, Institute of Genetic Medicine, Central Parkway, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK. Electronic address: david.young@ncl.ac.uk.
Newcastle University · GBAddenbrooke's Hospital · GBUniversity of Bristol · GBUniversity of East Anglia · GBUniversity of Manchester · GB

Funding

Arthritis Research UK 19424Department of HealthMedical Research Council MC_PC_12009Medical Research Council MC_UU_12013/2Medical Research Council MR/P020941/1The Dunhill Medical Trust R476/0516Versus Arthritis 19424
6 · The paper itself

Abstract

The Hedgehog (Hh) signalling pathway plays important roles during embryonic development and in adult tissue homeostasis, for example cartilage, where its deregulation can lead to osteoarthritis (OA). microRNAs (miRNAs) are important regulators of gene expression, and have been implicated in the regulation of signalling pathways, including Hh, thereby impacting upon development and disease. Our aim was to identify the function of miRNAs whose expression is altered in OA cartilage. Here we identified an increase in miR-324-5p expression in OA cartilage and hypothesised that, as in glioma, miR-324-5p would regulate Hh signalling. We determined that miR-324-5p regulates osteogenesis in human mesenchymal stem cells (MSCs) and in mouse C3H10T1/2 cells. Luciferase reporter assays demonstrated that miR-324-5p directly regulated established targets GLI1 and SMO in human but not in mouse, suggesting species-dependent mechanism of Hh pathway regulation. Stable Isotope Labelling with Amino acids in Cell culture (SILAC), mass spectrometry and whole genome transcriptome analysis identified Glypican 1 (Gpc1) as a novel miR-324-5p target in mouse, which was confirmed by real-time RT-PCR, immunoblotting and 3'UTR-luciferase reporters. Knockdown of Gpc1 reduced Hh pathway activity, and phenocopied the effect of miR-324-5p on osteogenesis, indicating that miR-324-5p regulates Hh signalling in mouse via direct targeting of Gpc1. Finally, we showed that human GPC1 is not a direct target of miR-324-5p. Importantly, as well as identifying novel regulation of Indian Hedgehog (Ihh) signalling, this study demonstrates how a miRNA can show conserved pathway regulation in two species but by distinct mechanisms and highlights important differences between human diseases and mouse models.

Indexed as

3' Untranslated RegionsAdultAnimalsCartilageCell LineDisease Models, AnimalGene Expression RegulationGenes, ReporterGlypicansHedgehog ProteinsHumansLuciferasesMesenchymal Stem CellsMiceMicroRNAsOsteoarthritis3' Untranslated RegionsGLI1 protein, humanGlypicansHedgehog ProteinsLuciferasesMicroRNAsMIRN324 microRNA, humanRNA, Small InterferingSmoothened ReceptorSMO protein, humanZinc Finger Protein GLI1CartilageGlypicansHedgehog signallingmicroRNAOsteoarthritisOsteogenesisSILAC

Identifiers

PMID30193893
PMCPMC6456721
OpenAlexW2888600460

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.