TY - JOUR
T1 - Clinical magnetic resonance-enabled characterization of mono-iodoacetate-induced osteoarthritis in a large animal species
AU - Unger, Mark D.
AU - Murthy, Naveen S.
AU - Kanwar, Rahul
AU - Strand, Kasey A.
AU - Maus, Timothy P.
AU - Beutler, Andreas S.
N1 - Funding Information:
Support was provided by the National Institute of Neurological Disorders and Stroke (NINDS) under R01NS100725 (to A.S.B.) and by the Richard M. Schulze Family Foundation (to T.P. M. and A.S.B.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors would like to thank the veterinarians and veterinary personnel of the Department of Comparative Medicine, Mayo Clinic, for guidance, advice, and outstanding care and monitoring of animals. The authors would also like to thank Diane Sauter, R.T., Joe Kreidermacher, R.T., and Kyle Iverson, R.T. of the Department of Radiology, Mayo Clinic, for dedicated support in the operation of the MRI scanner for all studies.
Publisher Copyright:
© 2018 Unger et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/8
Y1 - 2018/8
N2 - Introduction Osteoarthritis (OA) is the most common form of arthritis. Medical and surgical treatments have yet to substantially diminish the global health and economic burden of OA. Due to recent advances in clinical imaging, including magnetic resonance imaging (MRI), a correlation has been established between structural joint damage and OA-related pain and disability. Existing preclinical animal models of OA are useful tools but each suffers specific roadblocks when translating structural MRI data to humans. Intraarticular injection of monoiodoacetate (MIA) is a reliable, well-studied method to induce OA in small animals but joint size discrepancy precludes the use of clinical grade MRI to study structural disease. The porcine knee is suited for clinical MRI and demonstrates homology with humans. We set out to establish the first large animal model of MIA-induced knee OA in swine characterized by structural MRI. Materials and methods Yucatan swine (n = 27) underwent ultrasound-guided injection of knees with 1.2, 4, 12, or 40 mg MIA. MRI was performed at several time points over 12 weeks (n = 54 knees) and images were assessed according to a modified clinical grading scheme. Knees were harvested and graded up to 35 weeks after injection. Results MIA-injected knees (n = 25) but not control knees (n = 29) developed gross degeneration. A total of n = 6,000 MRI measurements were recorded by two radiologists. MRI revealed progressive cartilage damage, bone marrow edema, erosions, and effusions in MIA-injected knees. Lesion severity and progression was influenced by time, dose, and inter-individual variability. Conclusions Intraarticular injection of MIA produced structural knee degradation that was reliably characterized using clinical MRI in swine. Destruction was progressive and, similar to human OA, lesion severity was heterogeneous between and within treatment groups.
AB - Introduction Osteoarthritis (OA) is the most common form of arthritis. Medical and surgical treatments have yet to substantially diminish the global health and economic burden of OA. Due to recent advances in clinical imaging, including magnetic resonance imaging (MRI), a correlation has been established between structural joint damage and OA-related pain and disability. Existing preclinical animal models of OA are useful tools but each suffers specific roadblocks when translating structural MRI data to humans. Intraarticular injection of monoiodoacetate (MIA) is a reliable, well-studied method to induce OA in small animals but joint size discrepancy precludes the use of clinical grade MRI to study structural disease. The porcine knee is suited for clinical MRI and demonstrates homology with humans. We set out to establish the first large animal model of MIA-induced knee OA in swine characterized by structural MRI. Materials and methods Yucatan swine (n = 27) underwent ultrasound-guided injection of knees with 1.2, 4, 12, or 40 mg MIA. MRI was performed at several time points over 12 weeks (n = 54 knees) and images were assessed according to a modified clinical grading scheme. Knees were harvested and graded up to 35 weeks after injection. Results MIA-injected knees (n = 25) but not control knees (n = 29) developed gross degeneration. A total of n = 6,000 MRI measurements were recorded by two radiologists. MRI revealed progressive cartilage damage, bone marrow edema, erosions, and effusions in MIA-injected knees. Lesion severity and progression was influenced by time, dose, and inter-individual variability. Conclusions Intraarticular injection of MIA produced structural knee degradation that was reliably characterized using clinical MRI in swine. Destruction was progressive and, similar to human OA, lesion severity was heterogeneous between and within treatment groups.
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U2 - 10.1371/journal.pone.0201673
DO - 10.1371/journal.pone.0201673
M3 - Article
C2 - 30075007
AN - SCOPUS:85052369368
SN - 1932-6203
VL - 13
JO - PLoS One
JF - PLoS One
IS - 8
M1 - e0201673
ER -