Assessment of biochemical methods to detect enzymatic depolymerization of polysaccharides

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Proteoglycans on bone tumor development

Proteoglycans, extracellular matrix components, exert several activities on bone cells and seem crucial for maintaining an appropriate number of osteoblasts and osteoclasts. The overall data strengthen a pro-bone resorptive role for proteoglycans, through the control of osteoprotegerin availability and of receptor activator of NF-κB ligand bioactivity. In parallel, proteoglycans participate in the control of tumor development at different levels, including bone tumor development and bone metastases dissemination. This dual role makes them good candidates as regulatory molecules in the vicious cycle between tumor proliferation and bone resorption observed during tumor development in bone site. Knowledge of the biological roles of these molecules in cancer biology, tumor angiogenesis and metastasis has promoted the development of drugs targeting them

Free-radical depolymerization with metallic catalysts of an exopolysaccharide produced by a bacterium isolated from a deep-sea hydrothermal vent polychaete annelid

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Development of scandium-exopolysaccharide complexes as a theranostic tool in bone oncology

International audienceThe anti-metastatic properties of an exopolysaccharide (EPS) derivative produced by a deep-sea hydrothermal bacterium, Alteromonas infernus, were favourably evaluated on bone remodeling [1]

Effects of a sulfated exopolysaccharide produced by Altermonas infernus on bone biology

The growth and differentiation of bone cells is controlled by various factors which can be modulated by heparan sulphates. Here, we investigated the effects of an oversulphated “heparin-like” exopolysaccharide (OS-EPS) on bone. We compared the effect of this compound with that of a native exopolysaccharide (EPS). Long-term administration of OS-EPS causes cancellous bone loss in mice due, in part, to an increase in the number of osteoclasts lining the trabecular bone surface. No significant difference in cancellous bone volume was found between EPS-treated mice and age-matched control mice, underlying the importance of sulphatation in trabecular bone loss. However, the mechanism sustaining this osteoporosis was unclear. To clarify OS-EPS activities, we investigated the effect of OS-EPS in osteogenesis. Our results demonstrated that OS-EPS inhibited osteoclastogenesis in two cell models. By surface plasmon resonance technique we revealed that OS-EPS can constitute a hetero-molecular complex OS-EPS/RANKL/RANK and that RANK had a higher affinity for RANKL pre-incubated with OS-EPS than for RANKL alone which would be in favour of an increase in bone resorption. However, in vitro, OS-EPS inhibit the early steps of osteoclast precursor adhesion and therefore inhibits the step of cell fusion. In addition, we showed that OS-EPS reduces the proliferation and accelerates osteoblastic differentiation, leading to strong inhibition of mineralized nodule formation, which would be in favour of an increase in bone resorption. Taken together, these data show different levels of bone resorption regulation by exopolysaccharides, most of them leading to proresorptive effects

Effects of a sulfated exopolysaccharide produced by Altermonas infernus on bone biology. Glycobiology 2011, 21, 781–795. Samples Availability: Available from the authors. © 2011 by the authors; licensee MDPI

Abstract: The growth and differentiation of bone cells is controlled by various factors, which can be modulated by heparan sulfates. Here, we investigated the effects of an oversulfated exopolysaccharide (OS-EPS) on the bone. We compared the effect of this compound with that of a native EPS. Long-term administration of OS-EPS causes cancellous bone loss in mice due, in part, to an increase in the number of osteoclasts lining the trabecular bone surface. No significant difference in cancellous bone volume was found between EPS-treated mice and age-matched control mice, underlying the importance of sulfation in trabecular bone loss. However, the mechanism sustaining this osteoporosis was unclear. To clarify OS-EPS activities, we investigated the effect of OS-EPS on osteogenesis. Our results demonstrated that OS-EPS inhibited osteoclastogenesis in two cell models. Using the surface plasmon resonance technique, we revealed that OS-EPS can form a hetero-molecular complex OS-EPS/receptor activator of NF-κB ligand (RANKL)/RANK and that RANK had a higher affinity for RANKL pre-incubated with OS-EPS than for RANKL alone, which would be in favor of an increase in bone resorption. However, in vitro, OS-EPS inhibited the early steps of osteoclast precursor adhesion and therefore inhibited the cell fusion step. In addition, we showed that OS-EPS reduced proliferation and accelerated osteoblastic differentiation, leading to strong inhibition of mineralized nodule formation, which would be in favor of an increase in bone resorption. Taken together, these data show different levels of bone resorption regulation by EPSs, most of them leading to proresorptive effects

Effect of low molecular weight fucoidan and low molecular weight heparin in a rabbit model of arterial thrombosis

Background: Therapeutic use of unfractionated heparin and low molecular weight heparins (LMWHs) is limited by hemorrhagic adverse effects. We compared the antithrombotic effect of LMW fucoidan (LMWF) and LMWH in an experimental model. Methods: Thrombosis was induced in femoral arteries of male New Zealand White rabbits by in situ induction of endothelial apoptosis with staurosporine (10(-5) M for 30 min). Starting the day before apoptosis induction, the animals received subcutaneous LMWF (15 mg/kg), LMWH (enoxaparin 2.5 mg/kg) or saline solution (control group) twice a day for 4 days. Results: The degrees of apoptosis and endothelial denudation were similar in the 3 groups. The thrombotic score was significantly lower in the LMWF group than in the LMWH and control groups (p = 0.01). Tissue factor expression was significantly lower in the LMWF group than in the control and LMWH groups (p = 0.01). The plasma concentration of tissue factor pathway inhibitor was significantly increased after LMWF injection (137 +/- 28 vs. 102 +/- 17; p = 0.01), whereas no change was observed after LMWH treatment. LMWF did not prolong the bleeding time or decrease platelet aggregation. Conclusions: LMWF appeared to be more effective than LMWH for preventing arterial thrombosis in this experimental model. LMWF also had a lower hemorrhagic risk than LMWH. Copyright (C) 2008 S. Karger AG, Basel

Glycidyl alkoxysilane reactivities towards simple nucleophiles in organic media for improved molecular structure definition in hybrid materials

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Viral degradation of marine bacterial exopolysaccharides

The identification of the mechanisms by which marine dissolved organic matter (DOM) is produced and regenerated is critical to develop robust prediction of ocean carbon cycling. Polysaccharides represent one of the main constituents of marine DOM and their degradation is mainly attributed to polysaccharidases derived from bacteria. Here, we report that marine viruses can depolymerize the exopolysaccharides (EPS) excreted by their hosts using 5 bacteriophages that infect the notable EPS producer, Cobetia marina DSMZ 4741. Degradation monitorings as assessed by gel electrophoresis and size exclusion chromatography showed that 4 out of 5 phages carry structural enzymes that depolymerize purified solution of Cobetia marina EPS. The depolymerization patterns suggest that these putative polysaccharidases are constitutive, endo-acting, and functionally diverse. Viral adsorption kinetics indicate that the presence of these enzymes provides a significant advantage for phages to adsorb onto their hosts upon intense EPS production conditions. The experimental demonstration that marine phages can display polysaccharidases active on bacterial EPS lead us to question whether viruses could also contribute to the degradation of marine DOM and modify its bioavailability. Considering the prominence of phages in the ocean, such studies may unveil an important microbial process that affects the marine carbon cycle