Exogenous glucosamine globally protects chondrocytes from the arthritogenic effects of IL-1β

The effects of exogenous glucosamine on the biology of articular chondrocytes were determined by examining global transcription patterns under normal culture conditions and following challenge with IL-1β. Chondrocytes isolated from the cartilage of rats were cultured in several flasks either alone or in the presence of 20 mM glucosamine. Six hours later, one-half of the cultures of each group were challenged with 10 ng/ml IL-1β. Fourteen hours after this challenge, RNA was extracted from each culture individually and used to probe microarray chips corresponding to the entire rat genome. Glucosamine alone had no observable stimulatory effect on the transcription of primary cartilage matrix genes, such as aggrecan, collagen type II, or genes involved in glycosaminoglycan synthesis; however, glucosamine proved to be a potent, broad-spectrum inhibitor of IL-1β. Of the 2,813 genes whose transcription was altered by IL-1β stimulation (P < 0.0001), glucosamine significantly blocked the response in 2,055 (~73%). Glucosamine fully protected the chondrocytes from IL-1-induced expression of inflammatory cytokines, chemokines, and growth factors as well as proteins involved in prostaglandin E(2 )and nitric oxide synthesis. It also blocked the IL-1-induced expression of matrix-specific proteases such as MMP-3, MMP-9, MMP-10, MMP-12, and ADAMTS-1. The concentrations of IL-1 and glucosamine used in these assays were supraphysiological and were not representative of the arthritic joint following oral consumption of glucosamine. They suggest, however, that the potential benefit of glucosamine in osteoarthritis is not related to cartilage matrix biosynthesis, but is more probably related to its ability to globally inhibit the deleterious effects of IL-1β signaling. These results suggest that glucosamine, if administered effectively, may indeed have anti-arthritic properties, but primarily as an anti-inflammatory agent

Action antagoniste de la glucosamine sur les effets délétères de l'interleukine-1 ou des compressions mécaniques sur la synthèse des protéoglycanes dans des cultures chondrocytaires

Texte intégral accessible uniquement aux membres de l'Université de LorraineEarly stages of articular disease are characterized by a breakdown of cartilage homeostasis notably due to a biosynthesis inhibition of matricial components. Our works concerns the IL-1 and mechanical compression deleterious effects in an articular cartilage damage observed in an origjnal model of chondrocyte culture .We first have determined the krey role of GIcAT-I (an enzyme implicated in GAGelongation chain) on the decrease of PG synthesis. Moreover, we have shown that glucosamine reserves the IL-1 mechanical compression-mediated effects on anabolic, catabolic enzymes and on differents pro-inflammatory parameters. The glucosamine beneficial effects can be in part explained by an action at the receptorial level and on activation of NF-kB. This study improves knowledge of beneficial glucosamine effects on articular osteoarthritic cartilage by the identification of two targets on IL-1 signaling pathways.Les phases précoces des atteintes articulaires se caractérisent par une rupture de l'homéostasie du cartilage due en particulier à une inhibition de synthèse des composants matriciels.Nos travaux étudient les effets délétères de l'IL-1 et de compressions mécaniques lors de l'atteinte cartilagineuse observée dans un modèle original de chondrocytes en culture. Nous avons dans un premier temps mis en évidence le rôle clé de la GIcAT-I (une enzyme impliquée dans l'élongation de la chaîne des GAGs) dans la baisse de synthèse des PGs.Nous montrons d'autre part que la glucosamine s'oppose aux effets induits par l''IL-I et/ou les compressions mécaniques à la fois sur des enzymes anaboliques, caraboliques, mais aussi sur différents paramètres pro-inflammatoires. Les effets bénéfiques de ceglucide s'expliquent en partie par une action an niveau réceptoriel sut la voie d'activation de NF-kB. Cette étude ameliore les connaissances de l'effet bénéfique de la glucosamine sur le cartilage articulaire arthrosique par l'identification de deux cibles de ce glucide sur la signalisation cellulaire de l'IL-L

Action antagoniste de la glucosamine sur les effets délétères de l'interleukine-1 ou des compressions mécaniques sur la synthèse des protéoglycanes dans des cultures chondrocytaires

Texte intégral accessible uniquement aux membres de l'Université de LorraineEarly stages of articular disease are characterized by a breakdown of cartilage homeostasis notably due to a biosynthesis inhibition of matricial components. Our works concerns the IL-1 and mechanical compression deleterious effects in an articular cartilage damage observed in an origjnal model of chondrocyte culture .We first have determined the krey role of GIcAT-I (an enzyme implicated in GAGelongation chain) on the decrease of PG synthesis. Moreover, we have shown that glucosamine reserves the IL-1 mechanical compression-mediated effects on anabolic, catabolic enzymes and on differents pro-inflammatory parameters. The glucosamine beneficial effects can be in part explained by an action at the receptorial level and on activation of NF-kB. This study improves knowledge of beneficial glucosamine effects on articular osteoarthritic cartilage by the identification of two targets on IL-1 signaling pathways.Les phases précoces des atteintes articulaires se caractérisent par une rupture de l'homéostasie du cartilage due en particulier à une inhibition de synthèse des composants matriciels.Nos travaux étudient les effets délétères de l'IL-1 et de compressions mécaniques lors de l'atteinte cartilagineuse observée dans un modèle original de chondrocytes en culture. Nous avons dans un premier temps mis en évidence le rôle clé de la GIcAT-I (une enzyme impliquée dans l'élongation de la chaîne des GAGs) dans la baisse de synthèse des PGs.Nous montrons d'autre part que la glucosamine s'oppose aux effets induits par l''IL-I et/ou les compressions mécaniques à la fois sur des enzymes anaboliques, caraboliques, mais aussi sur différents paramètres pro-inflammatoires. Les effets bénéfiques de ceglucide s'expliquent en partie par une action an niveau réceptoriel sut la voie d'activation de NF-kB. Cette étude ameliore les connaissances de l'effet bénéfique de la glucosamine sur le cartilage articulaire arthrosique par l'identification de deux cibles de ce glucide sur la signalisation cellulaire de l'IL-L

Action antagoniste de la glucosamine sur les effets délétères de l'interleukine-1 ou des compressions mécaniques sur la synthèse des protéoglycanes dans des cultures chondrocytaires

NANCY1-SCD Pharmacie-Odontologie (543952101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Application des techniques de thérapie génique aux maladies ostéo-articulaires

L’apparition du concept de gène médicament a considérablement élargi le champ d’application de la thérapie génique. Initialement développées pour les maladies génétiques ou certaines formes de cancer, les stratégies de transfert génique sont désormais étudiées en vue du traitement d’autres pathologies telles que les maladies ostéo-articulaires. La polyarthrite rhumatoïde a ainsi fait l’objet du premier essai clinique de thérapie génique pour le traitement d’une maladie non létale

Autologous endometrial cell co-culture improves human embryo development to high-quality blastocysts: a randomized controlled trial

International audienceDoes autologous endometrial cell co-culture (AECC) improve the number of good-quality blastocysts obtained by IVF/intracytoplasmic sperm injection (ICSI), compared with conventional embryo culture medium in a broad group of patients referred to assisted reproductive technology (ART)?Design: This interventional, randomized, double-blind study took place at Clinique Ovo from March 2013 to October 2015 and included 207 healthy patients undergoing an IVF or ICSI protocol, of which 71 were excluded before randomization. On the previous cycle, all participants underwent an endometrial biopsy at D5 to D7 post-ovulation, following which the endometrial cells were prepared for AECC.Results: The data demonstrated that AECC significantly increased the incidence of good-quality blastocysts compared with culture in conventional media (42.6% vs 28.4%, P < 0.001). No significant differences were found in pregnancy and live birth rates.Conclusion: This study demonstrated the benefits of AECC on blastocyst quality compared with conventional embryo culture medium, in a broader category of patients referred to ART as opposed to other studies that concentrated on specific causes of infertility only. However, limitations of the study design should be taken into consideration; the analysis was performed using embryos rather than patients and a follow-up of children born following the treatments could not be conducte