Degradation of small leucine-rich repeat proteoglycans by matrix metalloprotease-13: identification of a new biglycan cleavage site

A major and early feature of cartilage degeneration is proteoglycan breakdown. Matrix metalloprotease (MMP)-13 plays an important role in cartilage degradation in osteoarthritis (OA). This MMP, in addition to initiating collagen fibre cleavage, acts on several proteoglycans. One of the proteoglycan families, termed small leucine-rich proteoglycans (SLRPs), was found to be involved in collagen fibril formation/interaction, with some members playing a role in the OA process. We investigated the ability of MMP-13 to cleave members of two classes of SLRPs: biglycan and decorin; and fibromodulin and lumican. SLRPs were isolated from human normal and OA cartilage using guanidinium chloride (4 mol/l) extraction. Digestion products were examined using Western blotting. The identities of the MMP-13 degradation products of biglycan and decorin (using specific substrates) were determined following electrophoresis and microsequencing. We found that the SLRPs studied were cleaved to differing extents by human MMP-13. Although only minimal cleavage of decorin and lumican was observed, cleavage of fibromodulin and biglycan was extensive, suggesting that both molecules are preferential substrates. In contrast to biglycan, decorin and lumican, which yielded a degradation pattern similar for both normal and OA cartilage, fibromodulin had a higher level of degradation with increased cartilage damage. Microsequencing revealed a novel major cleavage site (... G(177)/V(178)) for biglycan and a potential cleavage site for decorin upon exposure to MMP-13. We showed, for the first time, that MMP-13 can degrade members from two classes of the SLRP family, and identified the site at which biglycan is cleaved by MMP-13. MMP-13 induced SLRP degradation may represent an early critical event, which may in turn affect the collagen network by exposing the MMP-13 cleavage site in this macromolecule. Awareness of SLRP degradation products, especially those of biglycan and fibromodulin, may assist in early detection of OA cartilage degradation

Accompagnement dans l’apprentissage de l’argumentation par une équipe pluridisciplinaire : quels effets sur les acteurs?

Dans le cadre du Cursus Master Ingénieur (CMI) de Biologie Santé Environnement (BSE) développé à l’Université de Lorraine en France, une équipe pluridisciplinaire propose aux étudiants de première année de cette formation une Activité de Mise en Situation (AMS). Par groupe de trois ou quatre, ils/elles doivent effectuer une recherche de documentation scientifique sur un sujet de société lié aux sciences pour ensuite élaborer un argumentaire pro- et anti- qui sera présenté oralement. L’équipe pédagogique accompagne les étudiants tout au long du processus, dans l’objectif de favoriser l’intégration et la réussite des nouveaux étudiants. Il s’agit aussi de renforcer des compétences construites au lycée, notamment des compétences informationnelles afin de faciliter l’appropriation de la littéracie universitaire. L’article examine la question des effets de ce dispositif d’accompagnement sur les étudiants et les accompagnants. L’analyse des résultats des étudiants, de leurs réponses à une enquête d’auto-évaluation, de celles des tuteurs lors d’entretiens semi-directifs indique que cette AMS contribue à l’acquisition de compétences et au développement de l’autonomie des étudiants. Les enseignants témoignent d’un changement de posture dans leur rôle d’accompagnant, changement qui transforme aussi leurs pratiques professionnelles dans d’autres cours.Within the framework of a master’s degree in Biological, Health and Environmental Engineering developed at the University of Lorraine in France, a multidisciplinary team offers first year students a Situational Awareness Activity (AMS). In groups of three or four, the students have to carry out scientific documentation research on a societal subject related to science and develop pro and con arguments that are then presented orally. The pedagogical team accompanies the students throughout the process, with the aim of fostering the integration and success of new students. It is also a question of reinforcing the skills built up in high school, in particular informational skills in order to facilitate the appropriation of university literacy. The article examines the effects of this support system on the students and their tutors. The analysis of the students' results, their answers to a self-evaluation survey and those of the tutors during semi-directive interviews indicate that this AMS contributes to the acquisition of skills and the development of students' autonomy. The teachers report a change of stance in their role as tutors, a change that also transforms their professional practices in other courses

Subchondral bone in osteoarthritis: a biologic link with articular cartilage leading to abnormal remodeling.

International audienceThis review deals with new findings highlighting the concept of cross-talk between subchondral bone tissue and articular cartilage that may be crucial for the initiation and/or progression of osteoarthritis. In this review, new factors either produced by subchondral bone tissue or modifying osteoblast metabolism, yet implicated in osteoarthritis, are discussed

Effect of retinoic acid on two glycosyltransferase activities in c6 cultured glioma cells

International audience1. Activity of two glycosyltransferases was studied in retinoic acid-treated C6 cultured glioma cells. 2. The beta-galactoside alpha 2,3-sialyltransferase transferring N-acetylneuramin onto the O-glycans residues of glycoproteins was activated up to twice after chronic treatment (from 24 to 96 hr) with all-trans retinoic acid. 3. No effect was observed for shorter treatments. 4. On the opposite, the N-glycan galactosyltransferase activity remained unchanged whatever the length of retinoic acid treatment was. 5. The activatory effect was not dependent on isomery, as all-trans and 13-cis retinoic acid isomers were both activators of the C6 glioma cell sialyltransferase. 6. Measurement of adhesion of retinoic acid-treated cells using labelled plasma membranes showed an enhancement of adhesion in correlation with enhancement of sialyltransferase activity

FACTEURS PREDICTIFS D'INSUFFISANCE RENALE AIGUE FONCTIONNELLE SOUS TRAITEMENT PAR INHIBITEURS DE L'ENZYME DE CONVERSION (ETUDE RETROSPECTIVE SUR DOSSIERS)

ANGERS-BU Médecine-Pharmacie (490072105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Study ofO-sialylation of glycoproteins in C6 glioma cells treated with retinoic acid

International audienc

Ascite chyleuse chez le cirrhotique (caractéristiques cliniques et prise en charge)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Study of o-glycan sialylation in c6 cultured glioma cells: Regulation of a β-galactoside α2,3 sialyltransferase activity by ca2+/calmodulin antagonists and phosphatase inhibitors

International audienc

Study of O-glycan sialylation in C6 cultured glioma cells: Evidence for post-translational regulation of Aβ-galactoside α2,3 sialyltransferase activity by N-glycosylation

International audienceWe have studied the Gal beta 1-3GalNAc-R alpha 2,3 sialyltransferase from C6 glioma cells transferring Neu5Ac from CMP-Neu5Ac onto O-glycans of glycoproteins. Using synchronized C6 glioma cells, we showed that the alpha 2,3 sialyltransferase activity was inhibited by tunicamycin to a greater extend than DNA and protein biosynthesis suggesting inhibition of N-glycosylation of this enzyme. Additional demonstration of N-glycosylation of the alpha 2,3 sialytransferase was provided through ConA-Sepharose binding. Treatment of partially purified alpha 2,3 sialytransferase by peptide-N-glycosidase F showed a significative inhibition demonstrating that N-glycan moiety is required for complete activity of the C6 glioma cell alpha 2,3 sialyltransferase