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Toxicologic Pathology
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Articles

Anatomical Localization of Cartilage Degradation Markers in a Surgically Induced Rat Osteoarthritis Model

Lyn M. Wancket1, Vijay Baragi2, Susan Bove2, Kenneth Kilgore2, Peter J. Korytko3 and Roberto E. Guzman3

1 College of Veterinary Medicine, University of Illinois, Urbana, Illinois, USA
2 Inflammation Pharmacology, Pfizer Global Research and Development, Ann Arbor, Michigan, USA
3 Safety Sciences, Pfizer Global Research and Development, Ann Arbor, Michigan, USA

Correspondence: Address correspondence to: Roberto E. Guzman, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA; e-mail:roberto.guzman{at}pfizer.com

Osteoarthritis (OA) is a degenerative disease characterized by an irreversible loss of articular cartilage. Although surgically induced animal OA models are commonly used in drug efficacy assessment, degradation of type II collagen, an important component of articular cartilage is not routinely evaluated. Here, the medial meniscectomy surgical model (MMT) in Lewis rats was evaluated for proteoglycan loss with toluidine blue staining and collagen degradation with immunohistochemical staining for a collagen cleavage C-neoepitope, using a novel anti-type II collagen neoepitope antigen (TIINE) antibody. Femorotibial joints were collected for histology at 0 (no surgery), 3, 7, 14, 21, 28, 35, and 42 days postsurgery. Following MMT surgery, the medial tibial articular cartilage had proteoglycan matrix loss by day 3 that reached subchondral bone by days 28–42. Femoral cartilage damage occurred by day 14. TIINE staining was present at basal levels in growth plates and articular cartilage of all joints while all MMT-treated animals had increased intensity and area of staining in erosions that colocalized with proteoglycan loss. The MMT model produces a progressive pattern of cartilage damage resembling human OA lesions, making it useful, when evaluated with cartilage biomarkers, for assessing changes in cartilage degradation.

Key Words: Osteoarthritis • femorotibial joint • articular cartilage • meniscal tear • immunohistochemistry • collagen neoepitope • rat

Abbreviations: MMT, medial meniscal tear • OA, osteoarthritis • TIINE, type II neoepitope antigen

Toxicologic Pathology, Vol. 33, No. 4, 484-489 (2005)
DOI: 10.1080/01926230590965364
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