Showing papers on "Chondroitin sulfate published in 2003"
TL;DR: Surprisingly, nonsulfated chondroitin is indispensable in the morphogenesis and cell division of Caenorhabditis elegans, as revealed by RNA interference experiments of the recently cloned chondDetroitin synthase gene and by the analysis of mutants of squashed vulva genes.
671 citations
TL;DR: Combined glial fibrillary acidic protein (GFAP) immunohistochemistry and in situ hybridization demonstrated that GFAP astrocytes constituted a source of neurocan production after spinal cord injury, establishing a CSPG-rich matrix that persists for up to 2 months following injury.
535 citations
TL;DR: This study demonstrates the structural efficacy of glucosamine and indistinguishable symptomatic efficacies for both compounds in knee osteoarthritis and further studies are needed to investigate the relationship among time, dose, patient baseline characteristics, and structural efficacy for an accurate, disease-modifying characterization of these 2 compounds.
Abstract: Objective To assess the structural and symptomatic efficacy of oral glucosamine sulfate and chondroitin sulfate in knee osteoarthritis through independent meta-analyses of their effects on joint space narrowing, Lequesne Index, Western Ontario MacMaster University Osteoarthritis Index (WOMAC), visual analog scale for pain, mobility, safety, and response to treatment. Methods An exhaustive systematic research of randomized, placebo-controlled clinical trials published or performed between January 1980 and March 2002 that assessed the efficacy of oral glucosamine or chondroitin on gonarthrosis was performed using MEDLINE, PREMEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Current Contents, BIOSIS Previews, HealthSTAR, EBM Reviews, manual review of the literature and congressional abstracts, and direct contact with the authors and manufacturers of glucosamine and chondroitin. Inclusion, quality scoring, and data abstraction were performed systematically by 2 independent reviewers who were blinded to sources and authors. Conservative approaches were used for clear assessment of potential efficacy. Results Our results demonstrated a highly significant efficacy of glucosamine on all outcomes, including joint space narrowing and WOMAC. Chondroitin was found to be effective on Lequesne Index, visual analog scale pain, mobility, and responding status. Safety was excellent for both compounds. Conclusions Our study demonstrates the structural efficacy of glucosamine and indistinguishable symptomatic efficacies for both compounds. Regarding the relatively sparse data on glucosamine and joint space narrowing and the absence of data on structural effects of chondroitin, further studies are needed to investigate the relationship among time, dose, patient baseline characteristics, and structural efficacy for an accurate, disease-modifying characterization of these 2 compounds.
383 citations
TL;DR: Application of the method after nitrous acid treatment revealed that heparan sulfate and chondroitin sulfate ratio changed during muscle regeneration process and revealed significant modifications in the patterns of expression of different sulfated GAGs in these tissues.
Abstract: This article describes a simple and selective procedure used for direct measurement of sulfated glycosaminoglycans (GAGs) in biological samples and its application to the determination of GAGs during tissue regeneration and myogenic differentiation. We describe a modified procedure of previous GAG assays that has improved specificity, reproducibility, and sensitivity. The assay is based on the ability of sulfated GAGs to bind the cationic dye 1,9-dimethylmethylene blue. We describe conditions that allow isolation of the GAG-dye complex. This complex was dissociated; the optical density measurement of the dissociated dye permitted quantification of GAGs in biological samples. Applied to the study of myogenic cell differentiation in vitro, muscle repair, and skin ulceration, this method revealed significant modifications in the patterns of expression of different sulfated GAGs in these tissues. In particular, application of the method after nitrous acid treatment revealed that heparan sulfate and chondroitin sulfate ratio changed during muscle regeneration process.
329 citations
TL;DR: It is reported that blocking chondroitin synthesis results in cytokinesis defects in early embryogenesis, and cell division eventually stops, resulting in early embryonic death.
Abstract: Glycosaminoglycans such as heparan sulphate and chondroitin sulphate are extracellular sugar chains involved in intercellular signalling. Disruptions of genes encoding enzymes that mediate glycosaminoglycan biosynthesis have severe consequences in Drosophila and mice. Mutations in the Drosophila gene sugarless, which encodes a UDP-glucose dehydrogenase, impairs developmental signalling through the Wnt family member Wingless, and signalling by the fibroblast growth factor and Hedgehog pathways. Heparan sulphate is involved in these pathways, but little is known about the involvement of chondroitin. Undersulphated and oversulphated chondroitin sulphate chains have been implicated in other biological processes, however, including adhesion of erythrocytes infected with malaria parasite to human placenta and regulation of neural development. To investigate chondroitin functions, we cloned a chondroitin synthase homologue of Caenorhabditis elegans and depleted expression of its product by RNA-mediated interference and deletion mutagenesis. Here we report that blocking chondroitin synthesis results in cytokinesis defects in early embryogenesis. Reversion of cytokinesis is often observed in chondroitin-depleted embryos, and cell division eventually stops, resulting in early embryonic death. Our findings show that chondroitin is required for embryonic cytokinesis and cell division.
253 citations
TL;DR: Results show that gelatin/chondroitin sulfate/hyaluronan tri-copolymer has potential for use as a cartilage tissue engineering scaffold.
238 citations
TL;DR: Research is helping to clarify the mechanisms by which a variety of agents, such as glucosamine, chondroitin sulfate, hyaluronic acid, green tea, glucocorticoids, and nonsteroidal anti‐inflammatory drugs, can modify the symptoms and course of osteoarthritis.
Abstract: Articular cartilage is a complex tissue maintained by chondrocytes, which undergo metabolic changes as a result of aging, disease, and injury. These changes may hinder tissue maintenance and repair, resulting in accelerated loss of articular surface and leading to end-stage arthritis. Researchers are investigating both normal and pathologic cellular and molecular processes as well as the development of chondroprotective agents to improve the metabolic function of articular cartilage. Current research is helping to clarify the mechanisms by which a variety of agents, such as glucosamine, chondroitin sulfate, hyaluronic acid, green tea, glucocorticoids, and nonsteroidal anti-inflammatory drugs, can modify the symptoms and course of osteoarthritis. Also under investigation are methods of stimulating repair or replacing damaged cartilage, such as matrix metalloproteinase inhibitors, gene therapy, growth factors, cytokine inhibitors, and artificial cartilage substitutes. Tissue engineering, the combining of artificial matrices with cells and growth factors or genes, offers great potential for improving patient care.
237 citations
TL;DR: This is the first report of a GAG ligand for the TM7 receptors extending the already vast repertoire of stimuli of the GPCR superfamily.
203 citations
TL;DR: A sensitive and reproducible 96-well assay of uronic acid permitting a rapid processing of a number of samples with a very low consumption of reagents is described for the determination of complex uronic Acid-bearing polyanions such as hyaluronic acid, chondroitin sulfate, dermatan sulfate and heparin.
193 citations
TL;DR: It is reported here that the chondroitin polymerizing activity requires concomitant expression of a novel protein designated ChPF (ChPF) with mammalian ChSy, and results suggested that the ChPF acts as a specific activating factor for ChSy in chondDetroitin polymerization.
160 citations
TL;DR: It is concluded that heparinase III-sensitive, presumably undersulfated, cellular heparan sulfate plays a significant role in the biogenesis of PrPSc in ScN2a cells.
TL;DR: This work found that another member of aggrecan family, versican, biochemically binds to both HA and LP, and generated a molecular model of the B-B′ segment, in which a deletion and an insertion of B′ and B are critical for stable structure and HA binding.
TL;DR: It is concluded that glomerular size and charge selectivity in mice is similar to that previously shown for rats, and hyaluronic acid, chondroitin sulfate, and heparan sulfate are of importance for charge selection.
Abstract: This is the first functional study of glomerular size and charge selectivity in mice. The aim was to investigate the controversial issue of glomerular permselectivity in animals exposed to glucosaminoglycan-degrading enzymes, hyaluronidase, and heparinase. Fractional clearances (theta) for FITC-Ficoll and albumin were estimated in isoflurane anesthetized mice in vivo and in cooled isolated perfused kidneys (cIPK). In cIPK, a significant increase of theta(albumin) from 0.0023 (95% confidence interval, 0.0014 to 0.0033) in controls to 0.0130 (95% confidence interval, 0.0055 to 0.0206) was seen after hyaluronidase treatment. The theta for neutral Ficoll of similar size as albumin was 0.063 to 0.093 in all groups. According to a heterogeneous charged fiber model, the fiber volume fraction of negatively charged fibers decreased by 10% after enzyme treatments. It is concluded that glomerular size and charge selectivity in mice is similar to that previously shown for rats. Moreover, hyaluronic acid, chondroitin sulfate, and heparan sulfate are of importance for charge selectivity.
TL;DR: It is proposed that the neuritogenic property of the DSD-1 epitope may be attributable to a distinct CS structure characterized by the disulfated D disaccharide unit [GlcUA(2S)-GalNAc(6S)], and that this property may reflect the physiological neuritogenesis during brain development by mammalian oversulfated DS structures exemplified by the D SD- 1 epitope.
TL;DR: Detailed specificities of the three recombinant human 4-O-sulfotransferases using partially desulfated DS as an acceptor are examined, revealing for the first time that D4ST-1 most efficiently utilized GalNAc residues located not only in the sequence -Ido UA-GalNAc-IdoUA- but also in -GlcUA-Gal-NAc
TL;DR: IL-8-glycosaminoglycan interactions determine the location where IL-8 binds in lung tissue and provides a site for the dimerization of IL-9, which increases the local concentration of IL -8 in the lungs.
Abstract: Interleukin (IL)-8, a member of the CXC chemokine family, is a potent neutrophil chemotactic factor. Mechanisms that regulate the activity of chemokines in tissue are not clear. The goal of this study was to determine whether IL-8-glycosaminoglycan interactions are responsible for the binding of IL-8 in lung tissue. Experiments were performed with a quantitative tissue-binding assay to measure the amount of 125I-IL-8 binding and an in situ tissue-binding assay to characterize the location of IL-8 binding in lung tissue. Confocal microscopy demonstrated IL-8 binding to specific anatomic locations such as cell surfaces and extracellular matrix that were enriched with heparan sulfate and chondroitin sulfate. Removal of heparan sulfate or chondroitin sulfate from lung tissue significantly decreased the binding of 125I-IL-8. Two forms of IL-8 with single amino acid mutations in the glycosaminoglycan-binding domain showed decreased binding. In addition, studies with normal and monomeric IL-8 showed that dimerization increased the binding of 125I-IL-8 in lung tissue. These findings suggest that IL-8-glycosaminoglycan interactions determine the location where IL-8 binds in lung tissue and provides a site for the dimerization of IL-8, which increases the local concentration of IL-8 in the lungs.
TL;DR: The metabolic response of cartilage from aged animals to glcN and CS under simulated conditions of in vivo stress is significantly greater than that seen in nonstressed or young tissue.
TL;DR: The structure of chondroitinase ABC I provides a framework for probing specific functions of active-site residues for understanding the remarkably broad specificity of this enzyme and perhaps engineering a desired specificity.
TL;DR: This review focuses on the chemical and chemoenzymatic synthesis of glycosaminoglycan oligosaccharides, and recent advances in functional group protection chemistry, conversion of D-gluco to L-ido or D-galacto configurations, glycosylation reactions and the preparation and use of novel starting materials in acidic oligOSaccharide synthesis are discussed.
Abstract: Glycosaminoglycans, highly charged polycarboxylated, polysulfated polysaccharides, are an important class of therapeutic agents and investigational drug candidates. Heparin has been widely used as a clinical anticoagulant for over 60 years. Low molecular weight heparins have begun to displace heparin and recently a synthetic heparin pentasaccharide was approved for clinical use in Europe. In addition to heparin (and the related heparan sulfate glycosaminoglycan), dermatan sulfate, chondroitin sulfate, hyaluronan and their derivatives are all in various stages of clinical evaluation. This review focuses on the chemical and chemoenzymatic synthesis of glycosaminoglycan oligosaccharides. Recent advances in functional group protection chemistry, conversion of D-gluco to L-ido or D-galacto configurations, glycosylation reactions and the preparation and use of novel starting materials in acidic oligosaccharide synthesis are discussed.
TL;DR: Quantitative real-time PCR analysis revealed that CSGalNAcT-2 transcripts were highly expressed in the small intestine, leukocytes, and spleen, however, both CS GalNAcTs were ubiquitously expressed in various tissues.
TL;DR: Northern blot analysis revealed that the chondroitin GalNAcT-2 gene exhibited a ubiquitous but differing expression in human tissues, and the expression pattern differed from that of chond Detroitin GalN-acetylgalactosaminyltransferase, which was demonstrated to be redundancy in the chundroitinGalNAc transferases involved in the biosynthetic initiation and elongation of chONDroitin sulfate.
TL;DR: It is demonstrated that a functional, soluble form of the HTLV-1 surface envelope glycoprotein, gp46, fused to an immunoglobulin Fc region (gp46-Fc) binds to heparan sulfate proteoglycans (HSPGs) on mammalian cells.
Abstract: The major receptors required for attachment and entry of the human T-cell leukemia virus type 1 (HTLV-1) remain to be identified. Here we demonstrate that a functional, soluble form of the HTLV-1 surface envelope glycoprotein, gp46, fused to an immunoglobulin Fc region (gp46-Fc) binds to heparan sulfate proteoglycans (HSPGs) on mammalian cells. Substantial binding of gp46-Fc to HeLa and Chinese hamster ovary (CHO) K1 cells that express HSPGs was detected, whereas binding to the sister CHO lines 2244, which expresses no HSPGs, and 2241, which expresses no glycosaminoglycans (GAGs), was much reduced. Enzymatic removal of HSPGs from HeLa and CHO K1 cells also reduced gp46-Fc binding. Dextran sulfate inhibited gp46-Fc binding to HSPG-expressing cells in a dose-dependent manner, whereas chondroitin sulfate was less effective. By contrast, dextran sulfate inhibited gp46-Fc binding to GAG-negative cells such as CHO 2244, CHO 2241, and Jurkat T cells weakly or not at all. Dextran sulfate inhibited HTLV-1 envelope glycoprotein (Env)-pseudotyped virus infection of permissive, HSPG-expressing target cells and blocked syncytium formation between HTLV-1 Env-expressing cells and HSPG-expressing permissive target cells. Finally, HSPG-expressing cells were more permissive for HTLV-1 Env-pseudotyped virus infection than HSPG-negative cells. Thus, similar to other pathogenic viruses, HTLV-1 may have evolved to use HSPGs as cellular attachment receptors to facilitate its propagation.
Journal Article•
TL;DR: Topical application of glucosamine and chondroitin sulfate is effective in relieving the pain from OA of the knee and improvement is evident within 4 weeks.
Abstract: Objective. To assess the ability of a topical preparation of glucosamine sulfate and chondroitin sulfate to reduce pain related to osteoarthritis (OA) of the knee. Methods. Sixty-three patients were randomized to receive either a topical glucosamine and chon- droitin preparation or placebo to be used as required over an 8 week period. Efficacy was assessed using a visual analog scale (VAS) for pain as well as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the SF-36 questionnaire. Results. VAS scores indicated a greater mean reduction in pain for the glucosamine/chondroitin preparation group (mean change -3.4 cm, SD 2.6 cm) compared to the placebo group (mean change -1.6 cm, SD 2.7 cm) after 8 weeks. After 4 weeks the difference between active and placebo groups in their mean reduction from baseline was 1.2 (95% CI 0.1 to 2.4, p = 0.03) and after 8 weeks was 1.8 (95% CI for difference between groups, 0.6 to 2.9 cm; p = 0.002). Conclusion. Topical application of glucosamine and chondroitin sulfate is effective in relieving the pain from OA of the knee and improvement is evident within 4 weeks. (J Rheumatol 2003;30:523-8)
TL;DR: It is demonstrated that the LG4/5 modules within unprocessed laminin-5 permit its cell binding activity through heparan and chondroitin sulfate chains of syndecan-1 and reinforce previous data suggesting specific properties for the precursor molecule.
TL;DR: Variation of chondroitin sulfate plays important roles in the regulation of signal transduction in the brain, as seen in purified phosphacan from postnatal day 7 and P12 rat cerebral cortex and from P20 rat whole brain.
TL;DR: It is suggested that PTN-PTPζ signaling regulates the morphogenesis of Purkinje cell dendrites and that the mechanisms underlying that regulation involve the GLAST activity in Bergmann glial processes.
Abstract: PTPzeta/RPTPbeta, a receptor-type protein tyrosine phosphatase synthesized as a chondroitin sulfate (CS) proteoglycan, uses a heparin-binding growth factor pleiotrophin (PTN) as a ligand, in which the CS portion plays an essential role in ligand binding. Using an organotypic slice culture system, we tested the hypothesis that PTN-PTPzeta signaling is involved in the morphogenesis of Purkinje cell dendrites. An aberrant morphology of Purkinje cell dendrites such as multiple and disoriented primary dendrites was induced in slice cultures by (1) addition of a polyclonal antibody against the extracellular domain of PTPzeta, (2) inhibition of protein tyrosine phosphatase activity, (3) enzymatic removal of the CS chains, (4) addition of exogenous CS chains, and (5) addition of exogenous PTN, all of which disturb PTN-PTPzeta signaling. These treatments also reduced the immunoreactivity to GLAST, a glial glutamate transporter, on Bergmann glial processes. Furthermore, a glutamate transporter inhibitor also induced the abnormal morphogenesis of Purkinje cell dendrites. Altogether, these findings suggest that PTN-PTPzeta signaling regulates the morphogenesis of Purkinje cell dendrites and that the mechanisms underlying that regulation involve the GLAST activity in Bergmann glial processes.
TL;DR: The utility of reducing terminal derivatives and control of precursor ion charge state for tandem mass spectrometric strategies for determining GalNAc sulfation positional isomers of CS are described.
TL;DR: In this article, the various degree of methacrylate (MA) substitution on chondroitin sulfate (CS) was prepared by reacting chondro-in-sulfate with methacrylic anhydride (MAA) in the presence of sodium hydroxide (NaOH) as a base.
TL;DR: The enzymatic polymerization to provide synthetic chondroitin and its derivatives is reported here, the first example of such in vitro synthesis to date.
Abstract: The enzymatic polymerization to provide synthetic chondroitin and its derivatives is reported here, the first example of such in vitro synthesis to date. N-Acetylchondrosine (GlcAbeta(1-->3)GalNAc) oxazoline (1a) and its derivatives (1b-1f) were designed and synthesized as novel transition state analogue substrate monomers for catalysis by hyaluronidase. Hyaluronidase is a hydrolysis enzyme of chondroitin that also catalyzes the formation of repeated glycosidic bonds in in vitro synthesis, rather than in the catabolic direction. Monomers of 2-methyl (1a), 2-ethyl (1b), and 2-vinyl (1f) oxazoline derivatives were polymerized using this enzyme, via ring-opening polyaddition with total control of regioselectivity and stereochemistry. These reactions provided the corresponding synthetic chondroitin (natural type; N-acetyl, 2a) and the derivatives (unnatural type) with N-propionyl (2b) and N-acryloyl (2f) functional groups at the C2 position of all the galactosamine units, in good yields. Monomers of 2-n-propyl (1c) and 2-isopropyl (1d) oxazoline derivatives were polymerized to produce 2c and 2d in low yield. The 2-phenyl oxazoline derivative (1e) did not afford any enzyme-catalyzed products. M(n) values of 2a and 2b reached 4800 and 4000, respectively. The M(n) value of 2a corresponds to that of the naturally occurring chondroitin. Thus, hyaluronidase catalysis allows the in vitro production of not only natural type but also the formation of unnatural type chondroitins.