title: A Comprehensive Histological Assessment of Osteoarthritis Lesions in Mice.
abstract: OBJECTIVE
  Accurate histological assessment of osteoarthritis (OA) is critical in studies evaluating the effects of interventions on disease severity. The purpose of the present study was to develop a histological grading scheme that comprehensively and quantitatively assesses changes in multiple tissues that are associated with OA of the stifle joint in mice.
  
  
  METHODS
  Two representative midcoronal sections from 158 stifle joints, including naturally occurring and surgically induced OA, were stained with H&E and Safranin-O stains. All slides were evaluated to characterize the changes present. A grading scheme that includes both measurements and semiquantitative scores was developed, and principal components analysis (PCA) was applied to the resulting data from the medial tibial plateaus. A subset of 30 tibial plateaus representing a wide range of severity was then evaluated by 4 observers. Reliability of the results was evaluated using intraclass correlation coefficients (ICCs) and area under the receiver operating characteristic (ROC) curve.
  
  
  RESULTS
  Five factors were retained by PCA, accounting for 74% of the total variance. Interobserver and intraobserver reproducibilities for evaluations of articular cartilage and subchondral bone were acceptable. The articular cartilage integrity and chondrocyte viability factor scores were able to distinguish severe OA from normal, minimal, mild, and moderate disease.
  
  
  CONCLUSIONS
  This newly developed grading scheme and resulting factors characterize a range of joint changes in mouse stifle joints that are associated with OA. Overall, the newly developed scheme is reliable and reproducible, characterizes changes in multiple tissues, and provides comprehensive information regarding a specific site in the stifle joint.
authors.affiliation: Department of Veterinary Population Medicine, University of Minnesota College of Veterinary Medicine, St. Paul, MN, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: McNulty
authors.affiliation: Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Loeser
authors.affiliation: Biostatistical Design & Analysis Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Davey
authors.affiliation: Department of Orthopaedic Surgery, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Callahan
authors.affiliation: Department of Orthopaedic Surgery, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
authors.forename: Cristin M
authors.initials: CM
authors.lastname: Ferguson
authors.affiliation: Department of Veterinary Population Medicine, University of Minnesota College of Veterinary Medicine, St. Paul, MN, USA.
authors.forename: Cathy S
authors.initials: CS
authors.lastname: Carlson
keywords: histology; morphometry; murine; osteoarthritis