			Home About us Contact

Proteoglycan Degradation (proteoglycan + degradation)

Distribution by Scientific Domains

Medical Sciences	80%

Selected Abstracts

Regulation of human neutrophil-mediated cartilage proteoglycan degradation by phosphatidylinositol-3-kinase

IMMUNOLOGY, Issue 1 2001
C. S. T. Hii
Summary The ability of neutrophils to degrade cartilage proteoglycan suggests that the neutrophils that accumulate in the joints of rheumatoid arthritis patients are mediators of tissue damage. The regulatory mechanisms which are relevant to the proteoglycan-degrading activity of neutrophils are poorly understood. Since phosphatidylinositol 3-kinase (PI3-K), protein kinase C (PKC), the extracellular signal-regulated protein kinase (ERK)1/ERK2 and cyclic adenosine monophosphate (cAMP) have been reported to regulate neutrophil respiratory burst and/or degranulation, a role for these signalling molecules in regulating proteoglycan degradation was investigated. Preincubation of human neutrophils with GF109203X (an inhibitor of PKC), PD98059 (an inhibitor of MEK, the upstream regulator of ERK1/ERK2) or with forskolin or dibutyryl cAMP, failed to suppress proteoglycan degradation of opsonized bovine cartilage. In contrast, preincubation of neutrophils with wortmannin or LY294002, specific inhibitors of PI3-K, inhibited proteoglycan degradation. Incubation of neutrophils with cartilage resulted in the activation of PI3-K in neutrophils, consistent with a role for PI3-K in proteoglycan degradation. Activation of PI3-K and proteoglycan degradation was enhanced by tumour necrosis factor-,. Degradation caused by neutrophils from the synovial fluid of rheumatoid arthritis patients was also inhibited by wortmannin. These data demonstrate that the proteoglycan degradative activity of neutrophils required PI3-K but not PKC or the ERK1/ERK2/ERK5 cascades and was insensitive to increases in intracellular cAMP concentrations. [source]

Development of selective tolerance to interleukin-1, by human chondrocytes in vitro,

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2002
Greta M. Lee
Interleukin-1 induces release of NO and PGE2 and production of matrix degrading enzymes in chondrocytes. In osteoarthritis (OA), IL-1 continually, or episodically, acts on chondrocytes in a paracrine and autocrine manner. Human chondrocytes in chondron pellet culture were treated chronically (up to 14 days) with IL-1,. Chondrons from OA articular cartilage were cultured for 3 weeks before treatment with IL-1, (0.05,10 ng/ml) for an additional 2 weeks. Spontaneous release of NO and IL-1, declined over the pretreatment period. In response to IL-1, (0.1 ng/ml), NO and PGE2 release was maximal on Day 2 or 3 and then declined to near basal level by Day 14. Synthesis was recovered by addition of 1 ng/ml IL-1, on Day 11. Expression of inducible nitric oxide synthase (iNOS), detected by immunofluorescence, was elevated on Day 2 and declined through Day 14, which coordinated with the pattern of NO release. On the other hand, IL-1,-induced MMP-13 synthesis was elevated on Day 3, declined on Day 5, and then increased again through Day 14. IL-1, increased glucose consumption and lactate production throughout the treatment. IL-1, stimulated proteoglycan degradation in the early days and inhibited proteoglycan synthesis through Day 14. Chondron pellet cultures from non-OA cartilage released the same amount of NO but produced less PGE2 and MMP-13 in response to IL-1, than OA cultures. Like the OA, IL-1,-induced NO and PGE2 release decreased over time. In conclusion, with prolonged exposure to IL-1,, human chondrocytes develop selective tolerance involving NO and PGE2 release but not MMP-13 production, metabolic activity, or matrix metabolism. © 2002 Wiley-Liss, Inc. [source]

Mechanical injury potentiates proteoglycan catabolism induced by interleukin-6 with soluble interleukin-6 receptor and tumor necrosis factor , in immature bovine and adult human articular cartilage

ARTHRITIS & RHEUMATISM, Issue 10 2009
Yihong Sui
Objective Traumatic joint injury can damage cartilage and release inflammatory cytokines from adjacent joint tissue. The present study was undertaken to study the combined effects of compression injury, tumor necrosis factor , (TNF,), and interleukin-6 (IL-6) and its soluble receptor (sIL-6R) on immature bovine and adult human knee and ankle cartilage, using an in vitro model, and to test the hypothesis that endogenous IL-6 plays a role in proteoglycan loss caused by a combination of injury and TNF,. Methods Injured or uninjured cartilage disks were incubated with or without TNF, and/or IL-6/sIL-6R. Additional samples were preincubated with an IL-6,blocking antibody Fab fragment and subjected to injury and TNF, treatment. Treatment effects were assessed by histologic analysis, measurement of glycosaminoglycan (GAG) loss, Western blot to determine proteoglycan degradation, zymography, radiolabeling to determine chondrocyte biosynthesis, and Western blot and enzyme-linked immunosorbent assay to determine chondrocyte production of IL-6. Results In bovine cartilage samples, injury combined with TNF, and IL-6/sIL-6R exposure caused the most severe GAG loss. Findings in human knee and ankle cartilage were strikingly similar to those in bovine samples, although in human ankle tissue, the GAG loss was less severe than that observed in human knee tissue. Without exogenous IL-6/sIL-6R, injury plus TNF, exposure up-regulated chondrocyte production of IL-6, but incubation with the IL-6,blocking Fab significantly reduced proteoglycan degradation. Conclusion Our findings indicate that mechanical injury potentiates the catabolic effects of TNF, and IL-6/sIL-6R in causing proteoglycan degradation in human and bovine cartilage. The temporal and spatial evolution of degradation suggests the importance of transport of biomolecules, which may be altered by overload injury. The catabolic effects of injury plus TNF, appeared partly due to endogenous IL-6, since GAG loss was partially abrogated by an IL-6,blocking Fab. [source]