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Lessons from animal models of osteoarthritis

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Abstract

Animal models of osteoarthritis (OA) provide valuable insight into pathogenetic pathways. Although OA is not an inflammatory disease, synovial activation clearly plays a role. Matrix metalloproteinases 3 (stromelysin) and 13 (collagenase) appear crucial, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5-mediated aggrecan cleavage in the interglobular domain is key in OA cartilage damage. Apart from cytokines, chondrocyte derangement or hypertrophy may contribute. Enhanced discoidin domain receptor-2 expression is found in OA models and human OA. Moreover, deficiency of Runt-related transcription factor-2 ameliorates murine OA. The abundant transforming growth factor-β prevents chondrocyte hypertrophy. Age-related loss of proper transforming growth factor-β signaling, with a major drop in SMAD-2 phosphorylation, may contribute to hypertrophy and subsequent development of OA cartilage pathology. Finally, transgenic mice show that osteoprotegerin is protective in OA, and treatment studies with recombinant osteoprotegerin have identified chondrocyte apoptosis blocking as an underlying mechanism.

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Authors and Affiliations

  1. Rheumatology Research and Advanced Therapeutics, Radboud University Nijmegen Medical Center, Geert Grooteplein 26, 6525 GA, Nijmegen, The Netherlands

    Wim B. van den Berg

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  1. Wim B. van den Berg
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Correspondence to Wim B. van den Berg.

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van den Berg, W.B. Lessons from animal models of osteoarthritis. Curr Rheumatol Rep 10, 26–29 (2008). https://doi.org/10.1007/s11926-008-0005-x

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  • DOI: https://doi.org/10.1007/s11926-008-0005-x

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