Toward diagnostic relevance of theαVβ5,αVβ3,andαVβ6 integrins in OA:expression within human cartilage and spinal osteophytes  

作　　者：Edith Charlier Céline Deroyer Sophie Neuville Zelda Plener Olivier Malaise Federica Ciregia Philippe Gillet Gilles Reuter Mallory Salvé Nadia Withofs Roland Hustinx Dominique de Seny Michel G.Malaise 

机构地区：[1]Laboratory of Rheumatology,GIGA-I3,CHULiège,ULiège,Liège,Belgium [2]Department of Orthopaedic Surgery,CHULiège,Liège,Belgium [3]Department of Neurosurgery,CHULiège,Liège,Belgium [4]Department of Nuclear Medicine,CHULiège,Liège,Belgium

出　　处：《Bone Research》2020年第4期458-472,共15页骨研究（英文版）

基　　金：This study was supported by the“Fond d’Investissement pour la Recherche Scientifique”(FIRS),CHU de Liège,Belgium.

摘　　要：We previously reported 18FPRGD2 uptake by the coxofemoral lining,intervertebral discs and facet joint osteophytes in OA using PET/SCAN imaging.However,the molecular mechanism by which the PRGD2 tracer interacts with joint tissues and osteophytes in OA remains unclear.As PRGD2 ligands are expected to belong to the RGD-specific integrin family,the purpose of this study was(i)to determine which integrin complexes display the highest affinity for PRGD2-based ligands,(ii)to analyze integrin expression in relevant tissues,and(iii)to test integrin regulation in chondrocytes using OA-related stimuli to increase the levels of fibrosis and ossification markers.To this end,the affinity of PRGD2-based ligands for five heterodimeric integrins was measured by competition with 125I-echistatin.In situ analyses were performed in human normal vs.OA cartilage and spinal osteophytes.Osteophytes were characterized by(immuno-)histological staining.Integrin subunit expression was tested in chondrocytes undergoing dedifferentiation,osteogenic differentiation,and inflammatory stimulation.The integrinsαVβ5,αVβ3,andαVβ6 presented the highest affinity for PRGD2-based ligands.In situ,the expression of these integrins was significantly increased in OA compared to normal cartilage.Within osteophytes,the mean integrin expression score was significantly higher in blood vessels,fibrous areas,and cells from the bone lining than in osteocytes and cartilaginous zones.In vitro,the levels of integrin subunits were significantly increased during chondrocyte dedifferentiation(except forβ6),fibrosis,and osteogenic differentiation as well as under inflammatory stimuli.In conclusion,anatomical zones(such as OA cartilage,intervertebral discs,and facet joint osteophytes)previously reported to show PRGD2 ligand uptake in vivo expressed increased levels ofαVβ5,αVβ3,andβ6 integrins,whose subunits are modulated in vitro by OA-associated conditions that increase fibrosis,inflammation,and osteogenic differentiation.These results suggest that the increa

关 键 词：CARTILAGE inflammation FEMORAL 

分 类 号：R684.3[医药卫生—骨科学]