Comparative transcriptomic analysis of articular cartilage of post-traumatic osteoarthritis mouse models

Gilbert, Sophie J., Soul, Jamie, Hao, Yao, Lin, Hua, Piróg, Katarzyna A., Coxhead, Jonathan, Patel, Krutik, Barter, Matt J., Young, David A. and Blain, Emma J. ORCID: https://orcid.org/0000-0001-8944-4254 2024. Comparative transcriptomic analysis of articular cartilage of post-traumatic osteoarthritis mouse models. Disease Models & Mechanisms 17 (10) , dmm050583. 10.1242/dmm.050583

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Abstract

Animal models of post-traumatic osteoarthritis (PTOA) recapitulate the pathological changes observed in human PTOA. Here, skeletally mature C57Bl6 mice were subjected to either the rapid-onset, non-surgical, mechanical anterior cruciate ligament (ACL) rupture or surgical destabilisation of the medial meniscus (DMM) models. Transcriptome profiling of micro-dissected cartilage at day 7 and 42 post-ACL and DMM procedure respectively, showed that the two models were comparable and highly correlative (Spearman R =0.82, p<2.2E-16). Gene ontology enrichment analysis identified similarly enriched pathways, which were overrepresented by anabolic terms. To address the transcriptome changes more completely in the ACL model we also performed small RNA-seq, describing the first microRNA profile of this model. miR-199-5p was amongst the most abundant yet differentially expressed microRNAs and its inhibition in primary human chondrocytes led to a comparable transcriptome response to that observed in both human ‘OA damaged vs intact cartilage’ and murine DMM cartilage datasets. CELSR1, GIT1, ECE1 and SOS2 were all experimentally verified as novel miR-199-5p targets. Together, these data support the use of the ACL rupture model as a non-invasive companion to DMM.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	The Company of Biologists
ISSN:	1754-8403
Funders:	Versus Arthritis, MRC
Date of First Compliant Deposit:	9 October 2024
Date of Acceptance:	17 September 2024
Last Modified:	11 Nov 2024 14:15
URI:	https://orca.cardiff.ac.uk/id/eprint/172635

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