Proteoglycans in health and disease: structures and functions

Poole, A R

doi:10.1042/bj2360001

Cited by 435 publications

(213 citation statements)

References 248 publications

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“…Despite the ubiquity of this family of molecules, a wide variety of proteoglycans with characteristic sulfated GAG chains exhibit tissue-speci¢c and developmentally regulated expression (for a review, see [3]), and have been implicated in the regulation and maintenance of cell proliferation, cytodi¡erentiation, and tissue morphogenesis (for a review, see [4]). …”

Section: Introductionmentioning

confidence: 99%

Characterization of recombinant human glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan‐protein linkage region of proteoglycans

et al. 1999

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We characterized the recombinant glucuronyltransferase I (GlcAT-I) involved in the glycosaminoglycan-protein linkage region biosynthesis. The enzyme showed strict specificity for GalL L1-3GalL L1-4Xyl, exhibiting negligible incorporation into other galactoside substrates including GalL L1-3GalL L1-O-benzyl, GalL L1-4GlcNAc and GalL L1-4Glc. A comparison of the GlcAT-I with another L L1,3-glucuronyltransferase involved in the HNK-1 epitope biosynthesis revealed that the two L L1,3-glucuronyltransferases exhibited distinct and no overlapping acceptor substrate specificities in vitro. Nevertheless, the transfection of the GlcAT-I cDNA into COS-1 cells induced the significant expression of the HNK-1 epitope. These results suggested that the high expression of the GlcAT-I gene rendered the cells capable of synthesizing the HNK-1 epitope.z 1999 Federation of European Biochemical Societies.

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Section: Introductionmentioning

confidence: 99%

Characterization of recombinant human glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan‐protein linkage region of proteoglycans

et al. 1999

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“…This balance is disturbed in rheumatoid arthritis and other inflammatory or degenerative joint diseases [3,4]. Recent studies from several laboratories have demonstrated that the steady state metabolism of chondrocytes is affected by factors such as insulin-like growth factors IGF-I and IGF-II [5,6], transforming growth factor [7,8], and interleukin-1 (IL-1) [9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Interleukin‐1β induces synthesis and secretion of interleukin‐6 in human chondrocytes

et al. 1990

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Increased concentrations of interleukin‐6 (IL‐6) have been found in the synovial fluid of patients with osteoarthritis, rheumatoid arthritis and crystal‐related joint deseases. It is therefore of great interest to identify the cells responsible for the production of IL‐6, and to investigate whether IL‐6 plays a role in the pathogenesisof degenerative or inflammatory joint diseases. Here we show that human interleukin‐1β (IL‐1β) induces IL‐6 synthesis and secretion in differentiated human chondrocytes. In organ cultures resembling closely the in vivo system 106 chondrocytes incubated with 100 units of interleukin‐1β per ml of medium led to the release of 6 × 103 units of IL‐6 within 24 h. Chondrocytes cultured in agarose or as monolayers similary incubated with IL‐1β produced even higher amounts of IL‐6: 70 × 103 units per 106 cells within 24 h. The induction of IL‐6 synthesis by IL‐1β was also shown at the mRNA level. IL‐6 secreted by stimulated chondrocytes showed heterogeneity upon Western blot analysis.

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“…The only cells in cartilage, the chondrocytes, contribute less than 5% to the total volume (6) and are responsible for the synthesis and degradation of matrix components. Very little is known about the normal endogenous control mechanisms of matrix turnover in articular cartilage.…”

Section: Osteoarthritis (Oa)mentioning

confidence: 99%

Proteomic Analysis of Articular Cartilage Shows Increased Type II Collagen Synthesis in Osteoarthritis and Expression of Inhibin βA (Activin A), a Regulatory Molecule for Chondrocytes

Hermansson

Sawaji

Bolton

et al. 2004

Journal of Biological Chemistry

155

141

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We show that proteomic analysis can be applied to study cartilage pathophysiology. Proteins secreted by articular cartilage were analyzed by two-dimensional SDS-PAGE and mass spectrometry. Cartilage explants were cultured in medium containing [ 35 S]methionine/cysteine to radiolabel newly synthesized proteins. To resolve the cartilage proteins by two-dimensional electrophoresis, it was necessary to remove the proteoglycan aggrecan by precipitation with cetylpyridinium chloride. 50 -100 radiolabeled protein spots were detected on two-dimensional gels of human cartilage cultures. Of 170 silverstained proteins identified, 19 were radiolabeled, representing newly synthesized gene products. Most of these were known cartilage constituents. Several nonradiolabeled cartilage proteins were also detected. The secreted protein pattern of explants from 12 osteoarthritic joints (knee, hip, and shoulder) and 14 nonosteoarthritic adult joints were compared. The synthesis of type II collagen was strongly up-regulated in osteoarthritic cartilage. Normal adult cartilage synthesized little or no type II collagen in contrast to infant and juvenile cartilage. Potential regulatory molecules novel to cartilage were identified; pro-inhibin ␤A and processed inhibin ␤A (which dimerizes to activin A) were produced by all the osteoarthritic samples and half of the normals. Connective tissue growth factor and cytokine-like protein C17 (previously only identified as an mRNA) were also found. Activin induced the tissue inhibitor for metalloproteinases-1 in human chondrocytes. Its expression was induced in isolated chondrocytes by growth factors or interleukin-1. We conclude that type II collagen synthesis in articular cartilage is down-regulated at skeletal maturity and reactivated in osteoarthritis in attempted repair and that activin A may be an anabolic factor in cartilage. Osteoarthritis (OA)1 is a common joint disease characterized by degeneration of articular cartilage. Since cartilage has very limited capacity for repair, the loss is effectively irreversible. Prevalence studies show that most people over the age of 65 have some evidence of the disease (1, 2). Little is known about the molecular mechanism of cartilage destruction in OA, particularly the early events. It is thought that there is an imbalance between anabolism and catabolism of the extracellular matrix, there being an increase in catabolism. It has been suggested that this increased breakdown of matrix is due to the production of degradative enzymes such as the matrix metalloproteinases (MMPs) and members of the disintegrin and metalloproteinase (ADAM) family (3, 4). The increase in proteinase expression may be due to inflammatory cytokines such as interleukin-1 (Il-1) and tumor necrosis factor (4, 5). However, it is unclear whether these degradative processes are a primary event or a secondary reaction.Articular cartilage consists mainly of extracellular matrix, the principal organic components of which are type II collagen fibers and aggregates of the large proteoglycan...

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Proteoglycans in health and disease: structures and functions

Cited by 435 publications

References 248 publications

Characterization of recombinant human glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan‐protein linkage region of proteoglycans

Characterization of recombinant human glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan‐protein linkage region of proteoglycans

Interleukin‐1β induces synthesis and secretion of interleukin‐6 in human chondrocytes

Proteomic Analysis of Articular Cartilage Shows Increased Type II Collagen Synthesis in Osteoarthritis and Expression of Inhibin βA (Activin A), a Regulatory Molecule for Chondrocytes

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