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The glycosaminoglycan-binding domain of PRELP acts as a cell type–specific NF-κB inhibitor that impairs osteoclastogenesis

Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a glycosaminoglycan (GAG)- and collagen-binding anchor protein highly expressed in cartilage, basement membranes, and developing bone. We observed that PRELP inhibited in vitro and in vivo mouse osteoclastogenesis through its GAG-bindi...

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Autores principales: Rucci, Nadia, Rufo, Anna, Alamanou, Marina, Capulli, Mattia, Del Fattore, Andrea, Åhrman, Emma, Capece, Daria, Iansante, Valeria, Zazzeroni, Francesca, Alesse, Edoardo, Heinegård, Dick, Teti, Anna
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806584/
https://www.ncbi.nlm.nih.gov/pubmed/19951916
http://dx.doi.org/10.1083/jcb.200906014
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author Rucci, Nadia
Rufo, Anna
Alamanou, Marina
Capulli, Mattia
Del Fattore, Andrea
Åhrman, Emma
Capece, Daria
Iansante, Valeria
Zazzeroni, Francesca
Alesse, Edoardo
Heinegård, Dick
Teti, Anna
author_facet Rucci, Nadia
Rufo, Anna
Alamanou, Marina
Capulli, Mattia
Del Fattore, Andrea
Åhrman, Emma
Capece, Daria
Iansante, Valeria
Zazzeroni, Francesca
Alesse, Edoardo
Heinegård, Dick
Teti, Anna
author_sort Rucci, Nadia
collection PubMed
description Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a glycosaminoglycan (GAG)- and collagen-binding anchor protein highly expressed in cartilage, basement membranes, and developing bone. We observed that PRELP inhibited in vitro and in vivo mouse osteoclastogenesis through its GAG-binding domain ((hbd)PRELP), involving (a) cell internalization through a chondroitin sulfate– and annexin II–dependent mechanism, (b) nuclear translocation, (c) interaction with p65 nuclear factor κB (NF-κB) and inhibition of its DNA binding, and (d) impairment of NF-κB transcriptional activity and reduction of osteoclast-specific gene expression. (hbd)PRELP does not disrupt the mitogen-activated protein kinase signaling nor does it impair cell survival. (hbd)PRELP activity is cell type specific, given that it is internalized by the RAW264.7 osteoclast-like cell line but fails to affect calvarial osteoblasts, bone marrow macrophages, and epithelial cell lines. In vivo, (hbd)PRELP reduces osteoclast number and activity in ovariectomized mice, underlying its physiological and/or pathological importance in skeletal remodeling.
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spelling pubmed-28065842010-05-30 The glycosaminoglycan-binding domain of PRELP acts as a cell type–specific NF-κB inhibitor that impairs osteoclastogenesis Rucci, Nadia Rufo, Anna Alamanou, Marina Capulli, Mattia Del Fattore, Andrea Åhrman, Emma Capece, Daria Iansante, Valeria Zazzeroni, Francesca Alesse, Edoardo Heinegård, Dick Teti, Anna J Cell Biol Research Articles Proline/arginine-rich end leucine-rich repeat protein (PRELP) is a glycosaminoglycan (GAG)- and collagen-binding anchor protein highly expressed in cartilage, basement membranes, and developing bone. We observed that PRELP inhibited in vitro and in vivo mouse osteoclastogenesis through its GAG-binding domain ((hbd)PRELP), involving (a) cell internalization through a chondroitin sulfate– and annexin II–dependent mechanism, (b) nuclear translocation, (c) interaction with p65 nuclear factor κB (NF-κB) and inhibition of its DNA binding, and (d) impairment of NF-κB transcriptional activity and reduction of osteoclast-specific gene expression. (hbd)PRELP does not disrupt the mitogen-activated protein kinase signaling nor does it impair cell survival. (hbd)PRELP activity is cell type specific, given that it is internalized by the RAW264.7 osteoclast-like cell line but fails to affect calvarial osteoblasts, bone marrow macrophages, and epithelial cell lines. In vivo, (hbd)PRELP reduces osteoclast number and activity in ovariectomized mice, underlying its physiological and/or pathological importance in skeletal remodeling. The Rockefeller University Press 2009-11-30 /pmc/articles/PMC2806584/ /pubmed/19951916 http://dx.doi.org/10.1083/jcb.200906014 Text en © 2009 Rucci et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Rucci, Nadia
Rufo, Anna
Alamanou, Marina
Capulli, Mattia
Del Fattore, Andrea
Åhrman, Emma
Capece, Daria
Iansante, Valeria
Zazzeroni, Francesca
Alesse, Edoardo
Heinegård, Dick
Teti, Anna
The glycosaminoglycan-binding domain of PRELP acts as a cell type–specific NF-κB inhibitor that impairs osteoclastogenesis
title The glycosaminoglycan-binding domain of PRELP acts as a cell type–specific NF-κB inhibitor that impairs osteoclastogenesis
title_full The glycosaminoglycan-binding domain of PRELP acts as a cell type–specific NF-κB inhibitor that impairs osteoclastogenesis
title_fullStr The glycosaminoglycan-binding domain of PRELP acts as a cell type–specific NF-κB inhibitor that impairs osteoclastogenesis
title_full_unstemmed The glycosaminoglycan-binding domain of PRELP acts as a cell type–specific NF-κB inhibitor that impairs osteoclastogenesis
title_short The glycosaminoglycan-binding domain of PRELP acts as a cell type–specific NF-κB inhibitor that impairs osteoclastogenesis
title_sort glycosaminoglycan-binding domain of prelp acts as a cell type–specific nf-κb inhibitor that impairs osteoclastogenesis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806584/
https://www.ncbi.nlm.nih.gov/pubmed/19951916
http://dx.doi.org/10.1083/jcb.200906014
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