Inflammatory and degenerative phases resulting from anterior cruciate rupture in a non-invasive murine model of post-traumatic osteoarthritis

Gilbert, Sophie J., Bonnet, Cleo S., Stadnik, Paulina, Duance, Victor C. ORCID: https://orcid.org/0000-0002-7555-2016, Mason, Deborah J. ORCID: https://orcid.org/0000-0002-8666-6094 and Blain, Emma J. ORCID: https://orcid.org/0000-0001-8944-4254 2018. Inflammatory and degenerative phases resulting from anterior cruciate rupture in a non-invasive murine model of post-traumatic osteoarthritis. Journal of Orthopaedic Research 36 (8) , pp. 2118-2127. 10.1002/jor.23872

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Abstract

Joint injury is the predominant risk factor for post-traumatic osteoarthritis development (PTOA). Several non-invasive mouse models mimicking human PTOA investigate molecular mechanisms of disease development; none have characterised the inflammatory response to this acute traumatic injury. Our aim was to characterise the early inflammatory phase and later degenerative component in our in vivo non-invasive murine model of PTOA induced by anterior cruciate ligament (ACL) rupture. Right knees of 12-week-old C57Bl6 mice were placed in flexion at a 30° offset position and subjected to a single compressive load (12N, 1.4mm/s) to induce ACL rupture with no obvious damage to surrounding tissues. Tissue was harvested 4 hours post-injury and on days 3, 14 and 21; contralateral left knees served as controls. Histological, immunohistochemical and gene analyses were performed to evaluate inflammatory and degenerative changes. Immunohistochemistry revealed time-dependent expression of mature (F4/80 positive) and inflammatory (CD11b positive) macrophage populations within the sub-synovial infiltrate, developing osteophytes and inflammation surrounding the ACL in response to injury. Up-regulation of genes encoding acute pro-inflammatory markers, inducible nitric oxide synthase, interleukin-6 and interleukin-17, and the matrix degrading enzymes, ADAMTS-4 and MMP3 was detected in femoral cartilage, concomitant with extensive cartilage damage and bone remodelling over 21-days post-injury. Our non-invasive model describes pathologically distinct phases of the disease, increasing our understanding of inflammatory episodes, the tissues/cells producing inflammatory mediators and the early molecular changes in the joint, thereby defining the early phenotype of PTOA. This knowledge will guide appropriate interventions to delay or arrest disease progression following joint injury.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Additional Information:	This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Publisher:	Wiley
ISSN:	0736-0266
Funders:	Arthritis Research UK
Date of First Compliant Deposit:	20 March 2018
Date of Acceptance:	5 February 2018
Last Modified:	07 May 2023 13:00
URI:	https://orca.cardiff.ac.uk/id/eprint/109227

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