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Development of a microcomputed tomography scoring system to characterize disease progression in the Hartley guinea pig model of spontaneous osteoarthritis

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posted on 2017-12-11, 13:17 authored by Lauren B. Radakovich, Angela J. Marolf, John P. Shannon, Stephen C. Pannone, Vanessa D. Sherk, Kelly S. Santangelo

Aim: There is potential discrepancy between human and laboratory animal studies of osteoarthritis (OA), as radiographic assessment is the hallmark of the former and histopathology the standard for the latter. This suggests a need to evaluate OA in animal models in a manner similar to that utilized in people. Our study aimed to develop a whole joint grading scheme for microcomputed tomography (microCT) images in Hartley guinea pigs, a strain that recapitulates joint changes highlighted in human spontaneous OA. Materials and Methods: Knees from animals aged 2, 3, 5, 9, and 15 months were evaluated via whole joint microCT and standard histologic scoring. Quantitative microCT parameters, such as bone volume/total volume were also collected. Results: Both whole joint microCT and histologic scores increased with advancing age and showed strong correlation (r = 0.89. p < 0.0001). Histologic scores, which focus on cartilage changes, increased progressively with age. Whole joint microCT scores, which characterize bony changes, followed a stepwise pattern: scores increased between 3 and 5 months of age, stayed consistent between 5 and 9 months, and worsened again between 9 and 15 months. Conclusions: This work provides data that advocates the use of a whole joint microCT scoring system in guinea pig studies of OA, as it provides important information regarding bony changes that occur at a different rate than articular cartilage changes. This grading scheme, in conjunction with histology and quantitative microCT measurements, may enhance the translational value of this animal model as it pertains to human work.

Funding

This study was financially supported by internal university funding provided to Kelly S. Santangelo. This funding source had no role in: study design; collection, analysis, or interpretation of data; or in writing, editing, or other decisions regarding the manuscript. All imaging protocols and data were developed and acquired at the Animal Imaging Shared Resources (AISR, NJS) supported by the University of Colorado Cancer Center (NCI P30CA046934) and the Colorado Clinical and Translational Sciences Institute (NIH/NCATS UL1TR001082).

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