Histopathology of naturally occurring and surgically induced osteoarthritis in mice

M. A. McNulty, R. F. Loeser, C. Davey, M. F. Callahan, C. M. Ferguson, C. S. Carlson

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Objective: The morphology of lesions in mouse models of osteoarthritis (OA) has not been comprehensively characterized, in part because current histological assessments of OA focus primarily on articular cartilage (AC). In the present study, sections of murine stifle joints with naturally occurring (aged animals) and surgically induced (destabilized medial meniscus, DMM) OA were examined using a newly developed histological grading scheme that includes quantitative measurements and semiquantitative grades to evaluate multiple joint tissues. Design: The data collected was analyzed using Principal Components Analysis (PCA); factor scores for each joint were generated. Individual parameters and factor scores were compared between surgical groups and among age groups. For comparison, the original Mankin Histological-Histochemical Grading System (HHGS) also was applied. Results: Overall, lesions were most severe in the medial tibial plateaus. Significant changes in AC and neighboring bone were identified in surgically induced models and in naturally occurring disease. Mean factor scores provided a comprehensive evaluation of joint changes. An important new finding was that chondrocyte cell death within the AC was a commonly identified lesion and its extent significantly increased with age. While the Mankin HHGS detected significant overall differences in OA severity between surgical groups, it was not sensitive in detecting age-related differences, nor did it provide information regarding changes in individual tissues. Conclusion: These results demonstrate the utility of this newly developed murine OA grading scheme in identifying lesions in AC and in other joint tissues. Surgically induced changes were similar to those occurring naturally with aging.

Original languageEnglish (US)
Pages (from-to)949-956
Number of pages8
JournalOsteoarthritis and Cartilage
Issue number8
StatePublished - Aug 2012

Bibliographical note

Funding Information:
The authors would like to thank Josh Parker and Anne Undersander for their technical help with this project. Funding for this project was supported in part by the NIH Musculoskeletal Research Training Grant ( T32 AR050938 , CSC, MAM), the NIH Orthopaedics and Skeletal Biology Training Grant ( T32 AR052272 , MAM), an Arthritis Foundation Innovative Research Grant (RFL), and the Wake Forest University Translational Science Institute (RFL).


  • Histology
  • Morphometry
  • Murine
  • Osteoarthritis


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