Glycosaminoglycans modulate inflammation and apoptosis in LPS‐treated chondrocytes

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.

Nano-scale encapsulation enhances allograft survival and function of islets transplanted in a mouse model of diabetes

“…4d). Chondroitin-4-sulphate-PC, an anti-coagulatory molecule [31,32], was found to provide a better protective effect than alginate. Based on the findings above, the coating scheme adopted for our in vivo experiments used chitosan-PC and alginate in repeated layers, with the last layer being chondroitin-4-sulphate-PC.…”

“…In the current study, we aimed to adapt this technology to produce a conformal nano-coating for islets, which covers individual islets in nano-layers that possess anti-coagulation and antiinflammatory properties [31,32], thus achieving effective encapsulation without significantly increasing the size of the islet. Charged linear polysaccharides carrying phosphorylcholine (PC) modification were used as coating materials (Fig.…”

Encapsulation technologies in beta cell replacement therapies for Type 1 diabetes

“…Although alginate remains the most popular hydrogel of choice, agarose [115,116], chitosan [117], methacrylic acid [118], methyl methacrylate [119], polyamide [120,121], PVA [122], PEG [123,124], 2-hydroxyethyl methacrylate (HEMA) [125,126], AN69 (a copolymer of acrylonitrile and sodium-methallyl sulfonate) [127], and collagens type I and IV [128] are all being evaluated for use in islet and stem cell encapsulation. Stimuli-responsive synthetic hydrogels are commonly employed in cell encapsulation and tissue engineering.…”

Chondroitin sulfate in the treatment of osteoarthritis: from in vitro studies to clinical recommendations

“…MMP-13 inhibition can happen through the inhibition of p38 and Erk1/2 activation [Holzmann et al 2006]. Different inhibitory potencies were demonstrated for CS-4 and CS-6 against MMPs in murine chondrocytes [Campo et al 2009a]. Differences between CS-6 and CS-4 were also recently shown in human cells.…”