Streamlining quantitative joint-wide medial femoro-tibial histopathological scoring of mouse post-traumatic knee osteoarthritis models
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 investiga...
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| Hauptverfasser: | , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
15 September 2023
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| In: |
Osteoarthritis and cartilage
Year: 2023, Jahrgang: 31, Heft: 12, Pages: 1602-1611 |
| ISSN: | 1522-9653 |
| DOI: | 10.1016/j.joca.2023.07.013 |
| Online-Zugang: | Resolving-System, kostenfrei, Volltext: https://doi.org/10.1016/j.joca.2023.07.013 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1063458423009172 
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| Verfasserangaben: | 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 |
MARC
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| 245 | 1 | 0 | |a Streamlining quantitative joint-wide medial femoro-tibial histopathological scoring of mouse post-traumatic knee osteoarthritis models |c 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 |
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| 520 | |a 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. | ||
| 650 | 4 | |a Histopathology | |
| 650 | 4 | |a Murine models | |
| 650 | 4 | |a Osteoarthritis | |
| 650 | 4 | |a Posttraumatic osteoarthritis | |
| 650 | 4 | |a Scoring | |
| 700 | 1 | |a Heller, Raban |d 1991- |e VerfasserIn |0 (DE-588)1119266696 |0 (DE-627)872623696 |0 (DE-576)479814627 |4 aut | |
| 700 | 1 | |a Blaker, Carina L. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Clarke, Elizabeth C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Smith, Susan M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Burkhardt, Daniel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Liu, Yolanda |e VerfasserIn |4 aut | |
| 700 | 1 | |a Stoner, Shihani |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zaki, Sanaa |e VerfasserIn |4 aut | |
| 700 | 1 | |a Shu, Cindy C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Little, Christopher B. |e VerfasserIn |4 aut | |
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