Une étude expérimentale de la fissuration de plaques métalliques en dynamique rapide

National audienceExperiments are achieved in dynamic cracking on thin notched metallic plates loaded by explosions. These experiments allowed to link the parameters - classes of materials with different ductilities, thickness of samples, kinds of loading - to the different ways of cracking. Cracking is characterised by the size and the shape of the crack, its fracture facies and propagation velocity.Des expérimentations sont réalisées sur la propagation dynamique de fissures dans des plaques métalliques minces, entaillées, sollicitées par explosions. Ces expériences ont permis de lier les paramètres - nature du matériau (en fonction de la ductilité), épaisseur des plaques, mode de chargement - à la fissuration qui se caractérise par la taille de fissure, son faciès et sa vitesse de propagation

Pharmacological disruption of insulin-like growth factor 1 binding to IGF-binding proteins restores anabolic responses in human osteoarthritic chondrocytes

Insulin-like growth factor 1 (IGF-1) has poor anabolic efficacy in cartilage in osteoarthritis (OA), partly because of its sequestration by abnormally high levels of extracellular IGF-binding proteins (IGFBPs). We studied the effect of NBI-31772, a small molecule that inhibits the binding of IGF-1 to IGFBPs, on the restoration of proteoglycan synthesis by human OA chondrocytes. IGFBPs secreted by human OA cartilage or cultured chondrocytes were analyzed by western ligand blot. The ability of NBI-31772 to displace IGF-1 from IGFBPs was measured by radiobinding assay. Anabolic responses in primary cultured chondrocytes were assessed by measuring the synthesis of proteoglycans in cetylpyridinium-chloride-precipitable fractions of cell-associated and secreted (35)S-labeled macromolecules. The penetration of NBI-31772 into cartilage was measured by its ability to displace (125)I-labeled IGF-1 from cartilage IGFBPs. We found that IGFBP-3 was the major IGFBP secreted by OA cartilage explants and cultured chondrocytes. NBI-31772 inhibited the binding of (125)I-labeled IGF-1 to IGFBP-3 at nanomolar concentrations. It antagonized the inhibitory effect of IGFBP-3 on IGF-1-dependent proteoglycan synthesis by rabbit chondrocytes. The addition of NBI-31772 to human OA chondrocytes resulted in the restoration or potentiation of IGF-1-dependent proteoglycan synthesis, depending on the IGF-1 concentrations. However, NBI-31772 did not penetrate into cartilage explants. This study shows that a new pharmacological approach that uses a small molecule inhibiting IGF-1/IGFBP interaction could restore or potentiate proteoglycan synthesis in OA chondrocytes, thereby opening exciting possibilities for the treatment of OA and, potentially, of other joint-related diseases

Nouveaux agents anti-inflammatoires en série N-(4-pyridyl)alcanesulfonamide

peer reviewedaudience: researcher, professional, studen