Optimization of histologic grading schemes in spontaneous and surgically-induced murine models of osteoarthritis

A. R. Armstrong, C. S. Carlson, A. K. Rendahl, R. F. Loeser

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To compare the Osteoarthritis Research Society International (OARSI) and Articular Cartilage Structure (ACS) grading schemes applied to multiple and single sections, along with additional histologic measures, in two mouse models of Osteoarthritis (OA). Methods: Six coronal histologic stifle joint sections were collected from 40 C57BL/6J mice, including aged mice with spontaneous OA (approximately 18 months of age; n = 15) and young (12-week-old) mice that either underwent destabilization of the medial meniscus (DMM) surgery (n = 15) or sham surgery (n = 10). Sections were evaluated with the standard OARSI (0–6) scheme, a modified OARSI scheme, the ACS (0–12) scheme, histomorphometry of cartilage and bone, and scoring of osteophytes (0–3) and synovial hyperplasia (0–3). Principal components analysis (PCA) was used to determine the features explaining the greatest variability among the sections. Results: The grading schemes performed similarly when applied to a single mid-coronal section or six total coronal sections per joint. OARSI grading produced similar results when applied to hematoxylin and eosin or toluidine blue-stained sections. Aged mice had higher severity scores in the LTP than DMM mice (mid-coronal OARSI grade aged = 2.3 and DMM = 1.1, p = 0.0006; ACS grade aged = 4.1 and DMM = 1.6, p = 0.0024). PCA resulted in retention of four factors that accounted for 78.4% of the total variance. Factor 1 (36.4%) included the OARSI grade, ACS grade, Toluidine blue grade, articular cartilage area and thickness and the osteophyte grade. Conclusions: Grading of a single mid-coronal section using either the OARSI or ACS schemes combined with osteophyte and histomorphometric measures can consistently define OA severity in mice.

Original languageEnglish (US)
Pages (from-to)536-546
Number of pages11
JournalOsteoarthritis and Cartilage
Volume29
Issue number4
DOIs
StatePublished - Apr 2021

Bibliographical note

Funding Information:
This project was supported by grants from the National Institute of Arthritis, Musculoskeletal, and Skin Disease ( R37-AR049003 and T32-AR050938 ) and the National Institute on Aging ( R01-AG044034 ). The study sponsors had no role in the study design, collection, analysis and interpretation of data; the writing of the manuscript; or the decision to submit the manuscript for publication.

Publisher Copyright:
© 2021 Osteoarthritis Research Society International

Keywords

  • Grading
  • Mouse
  • Osteoarthritis
  • Preclinical

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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