Article

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). 01/2009; 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.

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    • "This is one explanation why glucosamine and chondroitin reduce the otherwise NO-induced cell death of chondrocytes. In comparison to glucosamine and CS, hyaluronic acid exerted a very minor anti-inflammatory and antiapoptotic effect, while it significantly reduced NO levels [139]. "
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    International Journal of Rheumatology 08/2011; 2011:969012. DOI:10.1155/2011/969012
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    • "Decorin, a dermatan sulfate proteoglycan, has also proven protective effects in an OGDculture model (Santra et al., 2006). Apart from the brain, certain GAGs have also proven antiapoptotic/protective effects in other tissues such as chondrocytes (Campo et al., 2009; Lisignoli et al., 2001), lung (Singleton et al., 2010), liver (Campo et al., 2004) and heart (Saravanan and Shanmugam, 2009). Maximal protection in our experimental model of OGD/ reoxygenation was achieved at the concentration of 3 mM; this concentration significantly reduced LDH release after OGD and after the first and second hour of reoxygenation (Fig. 1B). "
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    • "This effect was associated with the reduction of NF-kB translocation and with the reduction of the MAP kinase signalling pathway through p38 and Erk1/2. Another study has pointed to the anti-apoptotic effect of both CS-4 and CS-6 in mouse articular chondrocytes [Campo et al. 2009a]. In vivo, it was shown in a "
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