Specific or related causes in the pathogenesis of osetoarthritis remain unclear despite a great deal of investigation. This justifies a new venue of research into other factors involved in degenerative joint disease . The study of joint lubrication, biotribology, has been fraught with conflicting theories, failure to adequately use molecular techniques, standardize merchanical assays and assign clinical importance to lubrication by synovial fluid. This investigation addresses the molecular of synovial lubrication of animal joints. A considerable literature has demonstrated that these rubbing and pressurized surfaces (i.e., bearings) have low frictional properties (1-4). These properties arise in part from the slippery nature of articular cartilage. Most reports actually deal with the rheology of synovial fluid and may incorrectly assume that its viscosity is the basis for joint lubrication (5-10). Direct measurements documents that synovial fluid lowers the coefficient of friction between cartilage bearings and certain artificial surfaces. A lubricating glycoprotein termed """"""""lubricin"""""""" from synovial fluid is responsible for this but no one has proposed a mechanism of how it does so or how to study it in vitro. An arthrotripsometer composed of latex oscillating against glass employed by the PI reproduced critical findings of previous studies using cartilage bearings. It isolated boundary mode lubrication measuring devices previously employed by others. Synovial fluid, saliva, and detergents are the only substances which display this activity (11). The observation that lubricin lubricated the latex: glass bearing is a recent discovery by the PI. This provides an experimental opportunity to implicate failed lubrication in the occurrence of degenerative joint disease in a large number of patients and to causally link this measure to lubricin. A low coefficient of friction (mu) is no necessarily a measure of wear protection but synovial fluid does in fact confer this property to cartilage (12). It is unknown if the absence or paucity of lubricin is significant to the initial or continued pathogenesis of either osteoarthritis or rheumatoid arthritis. This principal goal of this investigation is to develop new immunological probes and with these identify the concentration of lubricin in synovial fluid extracted from healthy and arthritic human joints.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AG001008-04
Application #
6603447
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Premen, Andre J
Project Start
2000-08-15
Project End
2004-07-31
Budget Start
2003-08-01
Budget End
2004-07-31
Support Year
4
Fiscal Year
2003
Total Cost
$103,082
Indirect Cost
Name
Rhode Island Hospital (Providence, RI)
Department
Type
DUNS #
075710996
City
Providence
State
RI
Country
United States
Zip Code
02903
Zappone, Bruno; Ruths, Marina; Greene, George W et al. (2007) Adsorption, lubrication, and wear of lubricin on model surfaces: polymer brush-like behavior of a glycoprotein. Biophys J 92:1693-708
Elsaid, Khaled A; Jay, Gregory D; Chichester, Clinton O (2007) Reduced expression and proteolytic susceptibility of lubricin/superficial zone protein may explain early elevation in the coefficient of friction in the joints of rats with antigen-induced arthritis. Arthritis Rheum 56:108-16
Rhee, David K; Marcelino, Jose; Baker, MacArthur et al. (2005) The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth. J Clin Invest 115:622-31
Elsaid, K A; Jay, G D; Warman, M L et al. (2005) Association of articular cartilage degradation and loss of boundary-lubricating ability of synovial fluid following injury and inflammatory arthritis. Arthritis Rheum 52:1746-55
Schaefer, Dirk B; Wendt, David; Moretti, Matteo et al. (2004) Lubricin reduces cartilage--cartilage integration. Biorheology 41:503-8
Jay, Gregory D; Elsaid, Khaled A; Zack, Jeffrey et al. (2004) Lubricating ability of aspirated synovial fluid from emergency department patients with knee joint synovitis. J Rheumatol 31:557-64
Elsaid, K A; Jay, G D; Chichester, C O (2003) Detection of collagen type II and proteoglycans in the synovial fluids of patients diagnosed with non-infectious knee joint synovitis indicates early damage to the articular cartilage matrix. Osteoarthritis Cartilage 11:673-80
Jay, G D; Harris, D A; Cha, C J (2001) Boundary lubrication by lubricin is mediated by O-linked beta(1-3)Gal-GalNAc oligosaccharides. Glycoconj J 18:807-15
Jay, G D; Tantravahi, U; Britt, D E et al. (2001) Homology of lubricin and superficial zone protein (SZP): products of megakaryocyte stimulating factor (MSF) gene expression by human synovial fibroblasts and articular chondrocytes localized to chromosome 1q25. J Orthop Res 19:677-87