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Proteoglycan 4 downregulation in a sheep meniscectomy model of early osteoarthritis

Young, A.A., McLennan, S., Smith, M.M., Smith, S.M., Cake, M.A., Read, R.A., Melrose, J., Sonnabend, D.H., Flannery, C.R. and Little, C.B. (2006) Proteoglycan 4 downregulation in a sheep meniscectomy model of early osteoarthritis. Arthritis Research and Therapy, 8 (2).

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Osteoarthritis is a disease of multifactorial aetiology characterised by progressive breakdown of articular cartilage. In the early stages of the disease, changes become apparent in the superficial zone of articular cartilage, including fibrillation and fissuring. Normally, a monolayer of lubricating molecules is adsorbed on the surface of cartilage and contributes to the minimal friction and wear properties of synovial joints. Proteoglycan 4 is the lubricating glycoprotein believed to be primarily responsible for this boundary lubrication. Here we have used an established ovine meniscectomy model of osteoarthritis, in which typical degenerative changes are observed in the operated knee joints at three months after surgery, to evaluate alterations in proteoglycan 4 expression and localisation in the early phases of the disease. In normal control joints, proteoglycan 4 was immunolocalised in the superficial zone of cartilage, particularly in those regions of the knee joint covered by a meniscus. After the onset of early osteoarthritis, we demonstrated a loss of cellular proteoglycan 4 immunostaining in degenerative articular cartilage, accompanied by a significant (p < 0.01) decrease in corresponding mRNA levels. Early loss of proteoglycan 4 from the cartilage surface in association with a decrease in its expression by superficial-zone chondrocytes might have a role in the pathogenesis of osteoarthritis.

Publication Type: Journal Article
Murdoch Affiliation: School of Veterinary and Biomedical Sciences
Publisher: BioMed Central
Copyright: © 2006 Fishman et al
Notes: This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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