Clinical magnetic resonance-enabled characterization of mono-iodoacetate-induced osteoarthritis in a large animal species

Mark D. Unger, Naveen S Murthy, Rahul Kanwar, Kasey A. Strand, Timothy Maus, Andreas S Beutler

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere0201673
JournalPLoS One
Volume13
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Iodoacetates
osteoarthritis
knees
Magnetic resonance
magnetic resonance imaging
Osteoarthritis
Animals
Magnetic Resonance Spectroscopy
Knee
Magnetic Resonance Imaging
Imaging techniques
animals
Swine
injection
Intra-Articular Injections
swine
lesions (animal)
Animal Models
Joints
animal models

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Clinical magnetic resonance-enabled characterization of mono-iodoacetate-induced osteoarthritis in a large animal species. / Unger, Mark D.; Murthy, Naveen S; Kanwar, Rahul; Strand, Kasey A.; Maus, Timothy; Beutler, Andreas S.

In: PLoS One, Vol. 13, No. 8, e0201673, 01.08.2018.

Research output: Contribution to journalArticle

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