Glycosaminoglycans modulate inflammation and apoptosis in LPS-treated chondrocytes.

Department of Biochemical, Physiological and Nutritional Sciences, Section of Medical Chemistry, School of Medicine, University of Messina, Policlinico Universitario, 98125 Messina, Italy.
Journal of Cellular Biochemistry (Impact Factor: 3.37). 12/2008; 106(1):83-92. DOI: 10.1002/jcb.21981
Source: PubMed

ABSTRACT Previous studies reported that hyaluronic acid (HA), chondroitin sulphate (CS) and heparan sulphate (HS) were able to reduce the inflammatory process in a variety of cell types after lipopolysaccharide (LPS) stimulation. The aim of this study was to investigate the anti-inflammatory effect of glycosaminoglycans (GAGs) in mouse articular chondrocytes stimulated with LPS. Chondrocyte treatment with LPS (50 microg/ml) generated high levels of TNF-alpha, IL-1beta, IL-6, IFN-gamma, MMP-1, MMP-13, iNOS gene expression and their related proteins, increased NO concentrations (evaluated in terms of nitrites formation), NF-kappaB activation and IkBalpha degradation as well as apoptosis evaluated by the increase in caspase-3 expression and the amount of its related protein. The treatment of chondrocytes using two different doses (0.5 and 1.0 mg/ml) of HA, chondroitin-4-sulphate (C4S), chondroitin-6-sulphate (C6S), HS, keratan sulphate (KS) and dermatan sulphate (DS) produced a number of effects. HA exerted a very small anti-inflammatory and anti-apoptotic effect while it significantly reduced NO levels, although the effect on iNOS expression and activity was extremely slight. C4S and C6S reduced inflammation mediators and the apoptotic process. C6S failed to decrease NO production, although iNOS expression and activity were significantly reduced. HS, like C4S, was able to reduce all the effects stimulated by LPS treatment. KS and DS produced no reduction in any of the parameters considered. These results give further support to the hypothesis that GAGs actively participate in the regulation of inflammatory and apoptotic processes.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Symptomatic Slow Acting Drugs for Osteoarthritis (SYSADOA), such as hyaluronic acid (HA), chondroitin sulfate (CS) and glucosamine (GlcN) are natural compounds, composed of repeating disaccharides, used to treat patients with osteoarthritis (OA). Many questions about the kinetics and mechanism of action of SYSADOA remain poorly answered. This review examines the data supporting oral absorption and body distribution of SYSADOA, and discusses their mechanism of action. SYSADOA are absorbed in the small intestine with a bioavailability ranging from 5 to 45% and accumulate in articular tissues. The mechanism of action of HA and CS differ in several aspects from that of GlcN. Being large molecules, HA and CS do not penetrate into chondrocytes, synoviocytes, osteoblast, osteoclast and osteocytes, and so elicit the anti-inflammatory effect by engaging membrane receptors, e.g. CD44, TLR4, ICAM1, with a resulting dual effect: impede the fragments of extracellular matrix engaging these receptors, cause of inflammatory reaction, and block the signal transduction pathways activated by the fragments and so diminish the nuclear translocation of pro-inflammatory transcription factors. GlcN penetrates into cells by means of glucose transporters. The primary effect of GlcN is associated to its ability to O-GlcNAcylate proteins and as a consequence, modulates their activity, e.g. decrease nuclear factor-κB nuclear translocation. GlcN may also affect the transcription of pro-inflammatory cytokines by epigenetic mechanisms. The characteristics of the mechanism of action support the use of CS combined with GlcN, and suggest that HA and CS shall be more effective in initial phases of OA.
    Pharmacology [?] Therapeutics 01/2014; · 7.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiological evidences suggested an inverse association between the use of glucosamine supplements and colorectal cancer (CRC) risk. In this study, the efficacy of glucosamine to attenuate dextran sodium sulfate (DSS)-induced colitis, a precancerous condition for CRC was evaluated. C57BL/6 mice were separated into three groups receiving glucosamine sulfate at concentrations of 0, 0.05 and 0.10% (w/w) of AIN-93G diet, respectively for 4 weeks. Colitis was induced by supplying two cycles (5 days per cycle) of 2% DSS in the animals' drinking water. Glucosamine supplementation at the level of 0.10% of the diet (w/w) reduced colitis-associated symptoms as measured by disease activity index (DAI). Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and NF-κB mRNA expression in the colonic mucosa was significantly lower in animals fed 0.10% glucosamine compared to those of the control group. Expression of the tight junction proteins ZO-1 and occludin was significantly higher in the 0.10% glucosamine-supplemented group compared to the other groups. Also, colonic protein expression of lipocalin 2, and serum concentrations of interleukin-8 (IL-8) and amyloid P component (SAP) were significantly reduced in the 0.10% glucosamine-supplemented group compared to the control group. These results suggest that glucosamine attenuates the colitis disease activity by suppressing NF-κB activation and related inflammatory responses.
    Journal of Gastroenterology and Hepatology 12/2013; · 3.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Glycosaminoglycans (GAGs) are a special group of carbohydrates with structures that clearly distinguishes them from glycoproteins, and exert biological effects beyond basic nutrition. The complex nature of cell-surface and GAG-related structures present in extracellular matrix has led to the neglect of this potential therapeutic site for a long time. Consideration about carbohydrates only as energy source has become reoriented because of their pivotal roles in many biological processes; however, scarce advances have been made on GAG characterization in foods. This review focuses on the potential consequences of dietary GAGs on human intestinal health, considering nutritional aspects and biological processes such as inflammation.
    Food Reviews International 01/2013; 29(2). · 2.54 Impact Factor