Characterization of osteoprotegerin binding to glycosaminoglycans by surface plasmon resonance: role in the interactions with receptor activator of nuclear factor kappaB ligand (RANKL) and RANK.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72680
Title:
Characterization of osteoprotegerin binding to glycosaminoglycans by surface plasmon resonance: role in the interactions with receptor activator of nuclear factor kappaB ligand (RANKL) and RANK.
Authors:
Théoleyre, S; Kwan Tat, S; Vusio, P; Blanchard, F; Gallagher, John T; Ricard-Blum, S; Fortun, Y; Padrines, M; Rédini, F; Heymann, D
Abstract:
Osteoprotegerin (OPG) is a decoy receptor for receptor activator of nuclear factor kappaB ligand (RANKL), a key inducer of osteoclastogenesis via its receptor RANK. We previously showed that RANK, RANKL, and OPG are able to form a tertiary complex and that OPG must be also considered as a direct effector of osteoclast functions. As OPG contains a heparin-binding domain, the present study investigated the interactions between OPG and glycosaminoglycans (GAGs) by surface plasmon resonance and their involvement in the OPG functions. Kinetic data demonstrated that OPG binds to heparin with a high-affinity (KD: 0.28 nM) and that the pre-incubation of OPG with heparin inhibits in a dose-dependent manner the OPG binding to the complex RANK-RANKL. GAGs from different structure/origin (heparan sulfate, dermatan sulfate, and chondroitin sulfate) exert similar activity on OPG binding. The contribution of the sulfation pattern and the size of the oligosaccharide were determined in this inhibitory mechanism. The results demonstrated that sulfation is essential in the OPG-blocking function of GAGs since a totally desulfated heparin loses its capacity to bind and to block OPG binding to RANKL. Moreover, a decasaccharide is the minimal structure that totally inhibits the OPG binding to the complex RANK-RANKL. Western blot analysis performed in 293 cells surexpressing RANKL revealed that the pre-incubation of OPG with these GAGs strongly inhibits the OPG-induced decrease of membrane RANKL half-life. These data support an essential function of the related glycosaminoglycans heparin and heparan sulfate in the activity of the triad RANK-RANKL-OPG.
Affiliation:
INSERM, ERI 7, Nantes, F-44035, France.
Citation:
Characterization of osteoprotegerin binding to glycosaminoglycans by surface plasmon resonance: role in the interactions with receptor activator of nuclear factor kappaB ligand (RANKL) and RANK. 2006, 347 (2):460-7 Biochem. Biophys. Res. Commun.
Journal:
Biochemical and Biophysical Research Communications
Issue Date:
25-Aug-2006
URI:
http://hdl.handle.net/10541/72680
DOI:
10.1016/j.bbrc.2006.06.120
PubMed ID:
16828054
Type:
Article
Language:
en
ISSN:
0006-291X
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorThéoleyre, S-
dc.contributor.authorKwan Tat, S-
dc.contributor.authorVusio, P-
dc.contributor.authorBlanchard, F-
dc.contributor.authorGallagher, John T-
dc.contributor.authorRicard-Blum, S-
dc.contributor.authorFortun, Y-
dc.contributor.authorPadrines, M-
dc.contributor.authorRédini, F-
dc.contributor.authorHeymann, D-
dc.date.accessioned2009-07-07T10:05:01Z-
dc.date.available2009-07-07T10:05:01Z-
dc.date.issued2006-08-25-
dc.identifier.citationCharacterization of osteoprotegerin binding to glycosaminoglycans by surface plasmon resonance: role in the interactions with receptor activator of nuclear factor kappaB ligand (RANKL) and RANK. 2006, 347 (2):460-7 Biochem. Biophys. Res. Commun.en
dc.identifier.issn0006-291X-
dc.identifier.pmid16828054-
dc.identifier.doi10.1016/j.bbrc.2006.06.120-
dc.identifier.urihttp://hdl.handle.net/10541/72680-
dc.description.abstractOsteoprotegerin (OPG) is a decoy receptor for receptor activator of nuclear factor kappaB ligand (RANKL), a key inducer of osteoclastogenesis via its receptor RANK. We previously showed that RANK, RANKL, and OPG are able to form a tertiary complex and that OPG must be also considered as a direct effector of osteoclast functions. As OPG contains a heparin-binding domain, the present study investigated the interactions between OPG and glycosaminoglycans (GAGs) by surface plasmon resonance and their involvement in the OPG functions. Kinetic data demonstrated that OPG binds to heparin with a high-affinity (KD: 0.28 nM) and that the pre-incubation of OPG with heparin inhibits in a dose-dependent manner the OPG binding to the complex RANK-RANKL. GAGs from different structure/origin (heparan sulfate, dermatan sulfate, and chondroitin sulfate) exert similar activity on OPG binding. The contribution of the sulfation pattern and the size of the oligosaccharide were determined in this inhibitory mechanism. The results demonstrated that sulfation is essential in the OPG-blocking function of GAGs since a totally desulfated heparin loses its capacity to bind and to block OPG binding to RANKL. Moreover, a decasaccharide is the minimal structure that totally inhibits the OPG binding to the complex RANK-RANKL. Western blot analysis performed in 293 cells surexpressing RANKL revealed that the pre-incubation of OPG with these GAGs strongly inhibits the OPG-induced decrease of membrane RANKL half-life. These data support an essential function of the related glycosaminoglycans heparin and heparan sulfate in the activity of the triad RANK-RANKL-OPG.en
dc.language.isoenen
dc.subject.meshBinding, Competitive-
dc.subject.meshBlotting, Western-
dc.subject.meshCarrier Proteins-
dc.subject.meshCell Line-
dc.subject.meshGlycoproteins-
dc.subject.meshGlycosaminoglycans-
dc.subject.meshHeparin-
dc.subject.meshHumans-
dc.subject.meshKinetics-
dc.subject.meshMembrane Glycoproteins-
dc.subject.meshModels, Biological-
dc.subject.meshOligosaccharides-
dc.subject.meshOsteoprotegerin-
dc.subject.meshProtein Binding-
dc.subject.meshRANK Ligand-
dc.subject.meshReceptor Activator of Nuclear Factor-kappa B-
dc.subject.meshReceptors, Cytoplasmic and Nuclear-
dc.subject.meshReceptors, Tumor Necrosis Factor-
dc.subject.meshSulfates-
dc.subject.meshSurface Plasmon Resonance-
dc.subject.meshTime Factors-
dc.titleCharacterization of osteoprotegerin binding to glycosaminoglycans by surface plasmon resonance: role in the interactions with receptor activator of nuclear factor kappaB ligand (RANKL) and RANK.en
dc.typeArticleen
dc.contributor.departmentINSERM, ERI 7, Nantes, F-44035, France.en
dc.identifier.journalBiochemical and Biophysical Research Communicationsen
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