Theoleyre, S., Tat, S.K., Vusio, P. et al. (7 more authors) (2006) Characterization of osteoprotegerin binding to glycosaminoglycans by surface plasmon resonance: Role in the interactions with receptor activator of nuclear factor kappa B ligand (RANKL) and RANK. Biochemical and Biophysical Research Communications, 347 (2). pp. 460-467. ISSN 0006-291X
Abstract
Osteoprotegerin (OPG) is a decoy receptor for receptor activator of nuclear factor κB 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2006 Elsevier Inc. All rights reserved. |
Keywords: | osteoprotegerin; RANKL; RANK; heparin-binding domain; glycosaminoglycan; proteoglycan; bone; bone matrix; surface plasmon resonance |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 14 Apr 2016 14:35 |
Last Modified: | 01 May 2016 01:24 |
Published Version: | http://dx.doi.org/10.1016/j.bbrc.2006.06.120 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.bbrc.2006.06.120 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:98252 |