Abstract
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.
Highlights
Proteoglycan 4 (PRG4), which is homologous to lubricin [1], superficial zone protein (SZP) [2], megakaryocyte-stimulating factor precursor [2] and camptodactyly-arthropathy-coxavarapericarditis protein [3], is a lubricating glycoprotein believed to be primarily responsible for boundary lubrication in synovial joints [4]
Modified Mankin scoring was significantly increased in the LTP COV (4.4 ± 1.2 to 17.6 ± 2.7; mean ± SD; p < 0.01) and LTP UNCOV (3.1 ± 1.1 to 6.7 ± 1.9; p < 0.01) regions after lateral meniscectomy; it remained unchanged in MTP COV (2.3 ± 0.9 to 4.3 ± 2.6) and MTP UNCOV (2.6 ± 1.2 to 4.3 ± 1.6) regions
There was a decrease in PRG4 immunostaining with a marked loss of PRG4-positive superficial zone chondrocytes in the degenerative cartilage of the lateral compartment
Summary
Proteoglycan 4 (PRG4), which is homologous to lubricin [1], superficial zone protein (SZP) [2], megakaryocyte-stimulating factor precursor [2] and camptodactyly-arthropathy-coxavarapericarditis protein [3], is a lubricating glycoprotein believed to be primarily responsible for boundary lubrication in synovial joints [4]. PRG4 is a component of synovial fluid and is synthesised by the superficial chondrocytes in both normal articular cartilage and synovial cells [6]. A thin layer of PRG4 is present at the surface of normal articular cartilage; the relative contributions of synthesis from superficial chondrocytes and from synovial cells to the formation of this layer remains to be established [7].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
