OATargets: a knowledge base of genes associated with osteoarthritis joint damage in animals.


Journal

Annals of the rheumatic diseases
ISSN: 1468-2060
Titre abrégé: Ann Rheum Dis
Pays: England
ID NLM: 0372355

Informations de publication

Date de publication:
03 2021
Historique:
received: 17 06 2020
revised: 21 08 2020
accepted: 09 09 2020
pubmed: 21 10 2020
medline: 28 6 2022
entrez: 20 10 2020
Statut: ppublish

Résumé

To collate the genes experimentally modulated in animal models of osteoarthritis (OA) and compare these data with OA transcriptomics data to identify potential therapeutic targets. PubMed searches were conducted to identify publications describing gene modulations in animal models. Analysed gene expression data were retrieved from the SkeletalVis database of analysed skeletal microarray and RNA-Seq expression data. A network diffusion approach was used to predict new genes associated with OA joint damage. A total of 459 genes were identified as having been modulated in animal models of OA, with ageing and post-traumatic (surgical) models the most prominent. Ninety-eight of the 143 genes (69%) genetically modulated more than once had a consistent effect on OA joint damage severity. Several discrepancies between different studies were identified, providing lessons on interpretation of these data. We used the data collected along with OA gene expression data to expand existing annotations and prioritise the most promising therapeutic targets, which we validated using the latest reported associations. We constructed an online database OATargets to allow researchers to explore the collated data and integrate it with existing OA and skeletal gene expression data. We present a comprehensive survey and online resource for understanding gene regulation of animal model OA pathogenesis.

Identifiants

pubmed: 33077471
pii: annrheumdis-2020-218344
doi: 10.1136/annrheumdis-2020-218344
pmc: PMC7892386
doi:

Types de publication

Journal Article Review Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

376-383

Subventions

Organisme : Versus Arthritis
ID : 22043
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P020941/1
Pays : United Kingdom
Organisme : The Dunhill Medical Trust
ID : R476/0516
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom

Informations de copyright

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: CBL has provided scientific consulting advice to Fidia Farmaceutici, Merck Serono, and Galapagos pharmaceuticals. He conducts preclinical research for and funded by numerous pharmaceutical companies, under research agreements negotiated with the University of Sydney or the Northern Sydney Local Health District.

Auteurs

Jamie Soul (J)

Skeletal Research Group, Biosciences Institute, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK jamie.soul@newcastle.ac.uk.

Matthew J Barter (MJ)

Skeletal Research Group, Biosciences Institute, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK.

Christopher B Little (CB)

Raymond Purves Bone and Joint Research Laboratories, Kolling Institute, The University of Sydney, St Leonards, New South Wales, Australia.

David A Young (DA)

Skeletal Research Group, Biosciences Institute, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK.

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