New surgical model of post-traumatic osteoarthritis: Isolated intra-articular bone injury in the rabbit

Authors

  • Kyla D. Huebner,

    1. Faculty of Medicine, Department of Surgery, McCaig Institute for Bone and Joint Health, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1
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  • Nigel G. Shrive,

    1. Faculty of Medicine, Department of Surgery, McCaig Institute for Bone and Joint Health, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1
    2. Department of Civil Engineering, Schulich School of Engineering, University of Calgary, 2500 University Drive N.W., Calgary, Alberta, Canada T2N 1N4
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  • Cyril B. Frank

    Corresponding author
    1. Faculty of Medicine, Department of Surgery, McCaig Institute for Bone and Joint Health, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1
    • Faculty of Medicine, Department of Surgery, McCaig Institute for Bone and Joint Health, University of Calgary, 3330 Hospital Drive N.W., Calgary, Alberta, Canada T2N 4N1. T: +1-403-220-4554; F: +1-403-283-7742
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Abstract

Osteoarthritis (OA) is a leading cause of disability worldwide. We hypothesized that inflammation following isolated intra-articular bone injury can stimulate post-traumatic OA and developed a rabbit model to test that concept. Sixty female New Zealand White Rabbits were used. Twenty-six experimental animals had two holes drilled into their right femoral-notch, 18 rabbits had sham surgery, and 16 were un-operated controls. Rabbits were euthanized in subgroups at 72 h, 3, 6, 9, and 52 weeks. Knees were assessed grossly and tissues collected. Cartilage and synovium were analyzed with histology and qPCR and subgroups compared statistically. All surgical joints showed gross and histological (modified Mankin score) cartilage damage after surgery, with experimentals worsening with time (p < 0.05). Cartilage qPCR showed fivefold increases in TGFβ (p < 0.05) expression at 72 h and 3 weeks with sixfold increases in MMP13 (p < 0.025) expression at 72 h. By 6 weeks, expression of these markers was similar to baseline levels. Synovial membrane thickening with increased cellularity was seen at both 9 and 52 weeks (p < 0.05). Short-term synovial inflammatory marker (IL-1β, IL-Ra, IL-6, and IL-8) expression was three- to fourfold increase in experimentals at 72 h (p < 0.01) returning to baseline levels by 3 weeks. Intra-articular bone injury creates early joint inflammation with some chronic synovial changes and progressive cartilage damage consistent with OA in adult rabbits. This model provides an exciting new avenue to potentially explore some relevant inflammatory drivers of OA without major mechanical variables. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 914–920, 2013

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