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Logo of arthrestherBioMed Centralbiomed central web sitesearchsubmit a manuscriptregisterthis articleArthritis Research & Therapy
Arthritis Res Ther. 2006; 8(2): R41.
Published online Jan 31, 2006. doi:  10.1186/ar1898
PMCID: PMC1526595
Proteoglycan 4 downregulation in a sheep meniscectomy model of early osteoarthritis
Allan A Young,corresponding author1 Susan McLennan,2 Margaret M Smith,1 Susan M Smith,1 Martin A Cake,3 Richard A Read,3 James Melrose,1 David H Sonnabend,1 Carl R Flannery,4 and Christopher B Little1
1Raymond Purves Research Laboratory, Institute of Bone and Joint Research, Royal North Shore Hospital, University of Sydney, Pacific Highway, St Leonards, NSW 2065, Australia
2Department of Endocrinology, Royal Prince Alfred Hospital and Department of Medicine, University of Sydney, Missenden Road, Camperdown, NSW 2050, Australia
3School of Veterinary and Biomedical Sciences, Murdoch University, South Street, Murdoch, WA 6150, Australia
4Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA
corresponding authorCorresponding author.
Allan A Young: al_young/at/
Received November 23, 2005; Revisions requested December 20, 2005; Revised January 10, 2006; Accepted January 12, 2006.
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.
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