Accelerated post traumatic osteoarthritis in a dual injury murine model

McCulloch, K., Huesa, C., Dunning, L., Litherland, G. J., Van 'T Hof, R. J., Lockhart, J. C. and Goodyear, C. S. (2019) Accelerated post traumatic osteoarthritis in a dual injury murine model. Osteoarthritis and Cartilage, 27(12), pp. 1800-1810. (doi: 10.1016/j.joca.2019.05.027) (PMID:31283983)

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Abstract

Objective: Joint injury involving destabilisation of the joint and damage to the articular cartilage (e.g., sports-related injury) can result in accelerated post-traumatic osteoarthritis (PTOA). Destabilised medial meniscotibial ligament (DMM) surgery is one of the most commonly used murine models and whilst it recapitulates Osteoarthritis (OA) pathology, it does not necessarily result in multi-tissue injury, as occurs in PTOA. We hypothesised that simultaneous cartilage damage and joint destabilisation would accelerate the onset of OA pathology. Methods: OA was induced in C57BL/6 mice via (a) DMM, (b) microblade scratches of articular cartilage (CS) or (c) combined DMM and cartilage scratch (DCS). Mice were culled 7, 14 and 28 days post-surgery. Microcomputed tomography (μCT) and histology were used to monitor bone changes and inflammation. Dynamic weight bearing, an indirect measure of pain, was assessed on day 14. Results: Osteophytogenesis analysis via μCT revealed that osteophytes were present in all groups at days 7 and 14 post-surgery. However, in DCS, osteophytes were visually larger and more numerous when compared with DMM and cartilage scratch (CS). Histological assessment of cartilage at day 14 and 28, revealed significantly greater damage in DCS compared with DMM and CS. Furthermore, a significant increase in synovitis was observed in DCS. Finally, at day 14 osteophyte numbers correlated with changes in dynamic weight bearing. Conclusion: Joint destabilisation when combined with simultaneous cartilage injury accelerates joint deterioration, as seen in PTOA. Thus, DCS provides a novel and robust model for investigating multiple pathological hallmarks, including osteophytogenesis, cartilage damage, synovitis and OA-related pain.

Item Type:Articles
Additional Information:This work was supported by a Programme Grant from Versus Arthritis (Grant #20199) and a PhD studentship from the University of West of Scotland.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Dunning, Mrs Lynette and Lockhart, Professor John and Huesa, Dr Carmen and McCulloch, Kendal and Litherland, Dr Gary and Goodyear, Professor Carl
Authors: McCulloch, K., Huesa, C., Dunning, L., Litherland, G. J., Van 'T Hof, R. J., Lockhart, J. C., and Goodyear, C. S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Osteoarthritis and Cartilage
Publisher:Elsevier
ISSN:1063-4584
ISSN (Online):1522-9653
Published Online:05 July 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Osteoarthritis and Cartilage 27(12):1800-1810
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
595151Lessening the burden of osteoarthritis: elucidating the pathogenic role of the PAR-2 Pathway.Carl GoodyearArthritis Research UK (ARTRESUK)20199III -IMMUNOLOGY