Arthritis proteoglycans

In various types of arthritis, proteoglycans may act as autoantigens, thus contributing to the pathologic feamres of these conditions. The amount of chondroitin sulfate in cartilage diminishes with age, whereas the amounts of keratan sulfate and hyaluronic acid increase. These changes may contribute to the development of osteoarthritis. Changes in the amounts of cer-... 

Greenwald, RA., Moy, W.W. and Lazarus, D. (1976). Degradation of cartilage proteoglycans and collagen by superoxide anions. Arthritis Rheum. 19, 799-806. 

Erwin WM et al (2006) Nucleus pulposus notochord cells secrete connective tissue growth factor and up-regulate proteoglycan expression by intervertebral disc chondrocytes. Arthritis Rheum 54(12) 3859-3867... 

Lubberts E, Joosten LA, van de Loo FA, van den Gersselaar LA, van den Berg WB Reduction of interleukin-17-induced inhibihon of chondrocyte proteoglycan synthesis in intact murine articular carhlage by interleukin-4. Arthritis Rheum 2000 43 1300-1306. 

Hardingham, T. and Bayliss, M. (1990). Proteoglycans of articular cartilage Changes in aging and in joint disease. Semin. Arthritis Rheum. 20,12-33. 

Potter, K., Kidder, L. H., Levin, I. W., Lewis, E. N. and Spencer, R. G. (2001) Imaging of collagen and proteoglycan in cartilage sections using Fourier transform infrared spectral imaging. Arthritis Rheum. 44, 846-55. 

Figure 1. Articular cartilage is partitioned in three phases, one solid phase and two fluid phases. Each fluid phase contains several species. Some of these species are exchangeable, at least partially water and ions can enter and leave the intrafibrillar space defined by collagen fibrils. Proteoglycans which are macromolecules are too large to be admitted into that space, at least in absence of osteo-arthritis. Water and ions can also be exchanged between the extrafibrillar phase and the exterior.

Owens J G, Kamerling S G, Stanton S R et al 1996 Effects of pretreatment with ketoprofen and phenylbutazone on experimentally induces synovitis in horses. American Journal of Veterinary Research 57 866-874 Palmoski M J, Brandt K D 1983 Benoxaprofen stimulates proteoglycan synthesis in normal canine knee cartilage in vitro Arthritis and Rheumatism 26 771-774 Pasargiklian M, Bianco S 1986 Perspectives in the treatment of reversible ainway obstruction. Respiration 50(suppl 2) 131-136... 

A number of cytokines have been implicated in the pathology of inflammatory disease. In particular the role of IL-1 has been extensively investigated. In-traarticular administration of IL-1 induces inflammatory changes identical to those seen in some animal models of chronic arthritis (PIO). IL-1 has been shown to mediate cartilage matrix degradation, inhibit synthesis of proteoglycans, induce the breakdown of bone matrix, and stimulate PGEj synthesis (D5, D12, M40). More recently lL-6 and TNF have been shown to have many of the properties attributed to IL-1 and it remains to be established which cytokines exert an effect in vivo. Increased levels of all three of these cytokines, IL-1, TNF, and IL-6, have also been reported in the synovial fluid from arthritic joints (N12). 

Monfort J, Tardif G, Reboul P, Mineau F, Roughley P, Pelletier JP, Martel-Pelletier J. Degradation of small leucine-rich repeat proteoglycans by matrix metalloprotease-13 identification of a new biglycan cleavage site. Arthritis Res Ther 2006 8 R26-R34. 

Guerassimov A, Zhang Y, Cartman A, Rosenberg LC, Esdaile J, Fitzcharles MA, Poole AR. Immune responses to cartilage link protein and the G1 domain of proteoglycan aggrecan in patients with osteoarthritis. Arthritis Rheum 1999 42 527-533. 

A component closely related immunologically to the proteoglycans of cartilage has been detected (S3) in increased amounts in synovial fluids from patients with gout, lupus, rheumatic fever, and septic arthritis. In each case the proteoglycan material is probably released from the articular cartilage during acute inflammation of the joint. 

A tissue-culture model of the breakdown of cartilage in rheumatoid arthritis has been made on the basis of quantitative aspects of the release of proteoglycans. The findings support the view that a significant component of cartilage breakdown may be mediated by the chondrocytes. 

Schmidt, T.A. et al.. Synthesis of proteoglycan 4 by chondrocyte subpopulations in cartilage explants, monolayer cultures, and resurfaced cartilage cultures. Arthritis Rheum, 2004.50(9) 2849-57. 

Flechtenmacher, J. et al, Recombinant human osteogenic protein 1 is a potent stimulator of the synthesis of cartilage proteoglycans and collagens by human articular chondrocytes. Arthritis Rheum, 1996.39(11) 1896-904. 

Roughley, P. J., Articular Cartilage and Changes in Arthritis Noncollagenous Proteins and Proteoglycans in the Extracellular Matrix ofCartilage. Arthritis Res, 2001, 3(6), 342-347. 

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