A Modified Comprehensive Grading System for Murine Knee Osteoarthritis: Scoring the Whole Joint as an Organ

Abstract

ObjectiveThis study aimed to develop a comprehensive but easy to apply histologic grading system to score osteoarthritic changes in the whole knee joint for both spontaneous and posttraumatic osteoarthritis (OA) mouse models. MethodsThe new OA grading scheme was developed based on extensive literature review and the authors experience in mouse OA models with relatively long periods of observation (up to 24 months of age or 24-week post-surgery). Semi-quantitative assessments of the histopathologic OA changes were applied to all four quadrants of the knee. Grading elements per quadrant were defined as follows: cartilage (0-7) including three new grading elements for early- and late-stage OA, respectively; osteophyte (0-2) covering chondro-osteophytes in both outer and inner joint margins; subchondral bone (0-2) containing subchondral bone thickening and destruction; synovitis (0-2) comprised of both synovial plica and intercondylar notch; and peri-articular tissues (0-2) highlighting ectopic chondrogenesis and ossification in the knee capsule, ligament, and musculature. ResultsStatistical analyses showed that the new grading system had high intra- and inter-observer reproducibility (Pearsons correlation coefficients r >0.9) for both experienced and novice scorers. Sensitivity and reliability analyses confirmed the ability of the new system to detect minimal OA progression between two timepoints with a two-week interval and to accurately identify tissue-specific OA severity within the knee joint. ConclusionsThe comprehensive histologic grading system presented here covers all-stage osteoarthritic changes in all major knee joint tissues of mice, which enable us to score OA severity for the whole joint reproducibly and accurately without software-assisted time-consuming measurements.