Streamlining quantitative joint-wide medial femoro-tibial histopathological scoring of mouse post-traumatic knee osteoarthritis models
Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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| Enthalten in: |
Osteoarthritis and cartilage - 31(2023), 12 vom: 15. Dez., Seite 1602-1611 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Haubruck, Patrick [VerfasserIn] |
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| Links: |
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| Themen: |
Histopathology |
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| Anmerkungen: |
Date Completed 27.11.2023 Date Revised 27.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.joca.2023.07.013 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM362134987 |
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| 100 | 1 | |a Haubruck, Patrick |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Streamlining quantitative joint-wide medial femoro-tibial histopathological scoring of mouse post-traumatic knee osteoarthritis models |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 27.11.2023 | ||
| 500 | |a Date Revised 27.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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%) | ||
| 520 | |a 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 Journal Article | |
| 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 |e verfasserin |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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