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Mono-Iodoacetate-Induced Histologic Changes in Subchondral Bone and Articular Cartilage of Rat Femorotibial Joints: An Animal Model of Osteoarthritis

Drug Safety Evaluation, Pfizer Global Research and Development, Ann Arbor, MI, USA, roberto.guzman@ pfizer.com

Mark G. Evans

Drug Safety Evaluation, Pfizer Global Research and Development, Ann Arbor, MI, USA

Susan Bove

Inflammation Pharmacology, Pfizer Global Research and Development, Ann Arbor, MI, USA

Brandy Morenko

Inflammation Pharmacology, Pfizer Global Research and Development, Ann Arbor, MI, USA

Kenneth Kilgore

Inflammation Pharmacology, Pfizer Global Research and Development, Ann Arbor, MI, USA

Osteoarthritis (OA) is a degenerative joint disease characterized by joint pain and a progressive loss of articular cartilage. Studies to elucidate the pathophysiology of OA have been hampered by the lack of a rapid, reproducible animal model that mimics both the histopathology and symptoms associated with the disease. Injection of mono-iodoacetate (MIA), an inhibitor of glycolysis, into the femorotibial joint of rodents promotes loss of articular cartilage similar to that noted in human OA. Here, we describe the histopathology in the subchondral bone and cartilage of rat (Wistar) knee joints treated with a single intra articular injection of MIA (1 mg) and sacrificed at 1, 3, 5, 7, 14, 28, and 56 days postinjection. Histologically, the early time points (days 1—7) were characterized by areas of chondrocyte degeneration/necrosis sometimes involving the entire thickness of the articular cartilage in the tibial plateaus and femoral condyles. Changes to the subchondral bone, as evidenced by increased numbers of osteoclasts and osteoblasts, were noted at by day 7. By 28 days, there was focal fragmentation and collapse of bony trabeculae with fibrosis and increased osteoclastic activity. By 56 days there were large areas of bone remodeling evidenced by osteoclastic bone resorption and newly formed trabeculae with loss of marrow hematopoietic cells. Subchondral cysts and subchondral sclerosis were present in some rats. In conclusion, intra-articular injection of MIA induces loss of articular cartilage with progression of subchondral bone lesions that mimic those of OA. This model offers a rapid and minimally invasive method to reproduce OA-like lesions in a rodent species.

Key Words: Monoiodoacetate • osteoarthritis • femorotibial joint • articular cartilage • subchondral bone • osteoclasts • animal model.

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Toxicologic Pathology, Vol. 31, No. 6, 619-624 (2003)
DOI: 10.1080/01926230390241800


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Guzman, R. E. Articles by Kilgore, K. Search for Related Content PubMed PubMed Citation Articles by Guzman, R. E. Articles by Kilgore, K. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Joint Disorders Osteoarthritis Social Bookmarking                         What's this?