Streamlining quantitative joint-wide medial femoro-tibial histopathological scoring of mouse post-traumatic knee osteoarthritis models

• Verfasst von: Haubruck, Patrick [VerfasserIn]
• Verfasst von: Heller, Raban [VerfasserIn]
• Verfasst von: Blaker, Carina L. [VerfasserIn]
• Verfasst von: Clarke, Elizabeth C. [VerfasserIn]
• Verfasst von: Smith, Susan M. [VerfasserIn]
• Verfasst von: Burkhardt, Daniel [VerfasserIn]
• Verfasst von: Liu, Yolanda [VerfasserIn]
• Verfasst von: Stoner, Shihani [VerfasserIn]
• Verfasst von: Zaki, Sanaa [VerfasserIn]
• Verfasst von: Shu, Cindy C. [VerfasserIn]
• Verfasst von: Little, Christopher B. [VerfasserIn]
• Titel: Streamlining quantitative joint-wide medial femoro-tibial histopathological scoring of mouse post-traumatic knee osteoarthritis models
• Verf.angabe: Patrick Haubruck, Raban Heller, Carina L. Blaker, Elizabeth C. Clarke, Susan M. Smith, Daniel Burkhardt, Yolanda Liu, Shihani Stoner, Sanaa Zaki, Cindy C. Shu, Christopher B. Little
• E-Jahr: 2023
• Jahr: 15 September 2023
• Umfang: 10 S.
• Fussnoten: Gesehen am 31.05.2024
• Titel Quelle: Enthalten in: Osteoarthritis and cartilage
• Ort Quelle: [Erscheinungsort nicht ermittelbar] : Elsevier, 1993
• Jahr Quelle: 2023
• Band/Heft Quelle: 31(2023), 12, Seite 1602-1611
• ISSN Quelle: 1522-9653
• DOI: doi:10.1016/j.joca.2023.07.013
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Histopathology
• Sach-SW: Murine models
• Sach-SW: Osteoarthritis
• Sach-SW: Posttraumatic osteoarthritis
• Sach-SW: Scoring
• K10plus-PPN: 1890396680

Abstract

Objectives - Histological scoring remains the gold-standard for quantifying post-traumatic osteoarthritis (ptOA) in animal models, allowing concurrent evaluation of numerous joint tissues. Available systems require scoring multiple sections/joint making analysis laborious and expensive. We investigated if a single section allowed equivalent quantitation of pathology in different joint tissues and disease stages, in three ptOA models. - Method - Male 10-12-week-old C57BL/6 mice underwent surgical medial-meniscal-destabilization, anterior-cruciate-ligament (ACL) transection, non-invasive-ACL-rupture, or served as sham-surgical, non-invasive-ACL-strain, or naïve/non-operated controls. Mice (n = 12/group) were harvested 1-, 4-, 8-, and 16-week post-intervention. Serial sagittal toluidine-blue/fast-green stained sections of the medial-femoro-tibial joint (n = 7/joint, 84 µm apart) underwent blinded scoring of 40 histology-outcomes. We evaluated agreement between single-slide versus entire slide-set maximum or median scores (weighted-kappa), and sensitivity/specificity of single-slide versus median/maximum to detect OA pathology. - Results - A single optimal mid-sagittal section showed excellent agreement with median (weighted-kappa 0.960) and maximum (weighted-kappa 0.926) scores. Agreement for individual histology-outcomes was high with only 19/240 median and 15/240 maximum scores having a weighted-kappa ≤0.4, the majority of these (16/19 and 11/15) in control groups. Statistically-significant histology-outcome differences between ptOA models and their controls detected with the entire slide-set were reliably reproduced using a single slide (sensitivity >93.15%, specificity >93.10%). The majority of false-negatives with single-slide scoring were meniscal and subchondral bone histology-outcomes (89%) and occurred in weeks 1-4 post-injury (84%). - Conclusion - A single mid-sagittal slide reduced the time needed to score diverse histopathological changes by 87% without compromising the sensitivity or specificity of the analysis, across a variety of ptOA models and time-points.