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Construction and evaluation of a clinically relevant model of septic arthritis

Lab Animal volume 52, pages 11–26 (2023)Cite this article

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Abstract

Despite the creation of several experimental animal models for the study of septic arthritis, a protocol detailing the development of a reliable and easily reproducible animal model has not yet been reported. The experimental protocol described herein for the development of a clinically relevant mouse model of septic arthritis includes two main study stages: the first stage consisting of the preparation of the mice and of the methicillin-resistant Staphylococcus aureus (MRSA) cultures, followed by direct inoculation of MRSA into the knee joints of C57BL/6J mice (25–40 min); and a second study stage consisting of multiple sample collection and data analysis (1–3 days). This protocol may be carried out by researchers skilled in mouse care and trained to work with biosafety-level-2 agents such as MRSA. The model of septic arthritis described here has demonstrated clinical relevance in developing intra-articular inflammation and cartilage destruction akin to that of human patients. Moreover, we describe methods for serum, synovial fluid and knee joint tissue analysis that were used to confirm the development of septic arthritis in this model, and to test potential treatments. This protocol confers the advantages of enabling granular evaluation of the pathophysiology of MRSA infection and of the efficacy of therapeutic medications; it may also be employed to study a range of native joint diseases beyond inflammatory pathologies alone.

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Fig. 1: Timeline of the protocol.
Fig. 2: Flow images of septic arthritis procedure.
Fig. 3: Evaluation of septic arthritis murine model and analysis of synovial fluid in septic arthritis.
Fig. 4: Evaluation of pathophysiological score in septic arthritis.

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Data availability

The data that support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

This research was supported by National Institutes of Health (NIH) National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) grants AR056246 and AR068353. We appreciate the histological assistance of N. Troiano and J. Fretz (Department of Orthopaedics and Rehabilitation, Yale School of Medicine).

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  1. Department of Orthopaedics and Rehabilitation, Yale University, School of Medicine, New Haven, CT, USA

    Hyuk-Kwon Kwon, Kristin E. Yu & Francis Y. Lee

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H.-K.K. conceptualized and performed all experiments. K.E.Y. analyzed the data. H.-K.K., K.E.Y. and F.Y.L. wrote the manuscript.

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Correspondence to Francis Y. Lee.

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Lab Animal thanks Tao Jin, Johann Volzke and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Visual instructions for Steps 7–9.

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Kwon, HK., Yu, K.E. & Lee, F.Y. Construction and evaluation of a clinically relevant model of septic arthritis. Lab Anim 52, 11–26 (2023). https://doi.org/10.1038/s41684-022-01089-7

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