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

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Bone Research 2020年第4期8卷 458-472页

作者： Edith charlier c.line 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 Laboratory of Rheumatology GIGA-I3CHULiègeULiègeLiègeBelgium Department of Orthopaedic Surgery CHULiègeLiègeBelgium Department of Neurosurgery CHULiègeLiègeBelgium Department of Nuclear Medicine CHULiègeLiègeBelgium

We previously reported 18FPRGD2 uptake by the coxofemoral lining,intervertebral discs and facet joint osteophytes in OA using PET/ScAN ***,the molecular mechanism by which the PRGD2 tracer interacts with joint tissues and osteophytes in OA remains *** 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 *** this end,the affinity of PRGD2-based ligands for five heterodimeric integrins was measured by competition with *** situ analyses were performed in human normal *** cartilage and spinal *** were characterized by(immuno-)histological *** subunit expression was tested in chondrocytes undergoing dedifferentiation,osteogenic differentiation,and inflammatory *** integrinsαVβ5,αVβ3,andαVβ6 presented the highest affinity for PRGD2-based *** situ,the expression of these integrins was significantly increased in OA compared to normal *** 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 *** vitro,the levels of integrin subunits were significantly increased during chondrocyte dedifferentiation(except forβ6),fibrosis,and osteogenic differentiation as well as under inflammatory *** 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.T

关键词： cartilage inflammation femoral

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