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Proteomic profile of osteoclast membrane proteins: Identification of Na+/H+ exchanger domain containing 2 and its role in osteoclast fusion

Cited 28 time in Web of Science Cited 27 time in Scopus
Authors
Ryoo, Hyun-Mo; Ha, Byung Geun; Hong, Jung Min; Park, Ju-Yong; Ha, Mi-Hyun; Kim, Tae-Ho; Cho, Je-Yeol; Choi, Je-Yong; Shin, Hong-In; Chun, So Young; Kim, Shin-Yoon; Park, Eui Kyun
Issue Date
2008-07
Publisher
Wiley-Blackwell
Citation
Proteomics 8, 2625-2639
Keywords
MacrophagesMembrane proteinsOsteoclastsRANKL
Abstract
Osteoclast formation and bone resorption are multiple processes that involve the participation of specialized membrane structures and their associated proteins. In this study, we used an MS to analyze the profile of proteins associated with osteoclast membranes and focused on the function of channel proteins in osteoclast differentiation and function. We filtered out with a SEQUEST score greater than 10 and a peptide hit number of more than 2, resulting in the identification of 499 proteins that were commonly found in both macrophages and osteoclasts, 96 proteins selectively found in osteoclasts, and 179 proteins selectively found in macrophages. The proteins that were selectively found in osteoclasts were classified based on their localizations: plasma membrane (17%), ER/Golgi and lysosome/endosome (15%), mitochondrion (18%), nucleus (13%), cytosol (19%), and unknown (18%). Proteins associated with osteoclast function such as v-ATPase, IGF2R, TRAP, and cathepsin K were found in osteoclasts as previously shown. We found several ion channel proteins such as Ank and Nhedc2 and signaling molecules such as Dock5 and RAB-10 in osteoclasts. Inhibition of the Na+/H+ exchanger family by amiloride suppressed RANKL-induced osteoclast fusion and bone resorption. In addition, shRNA for Nhedc2 inhibited osteoclast differentiation. Our results provide a proteomic profile of osteoclast membrane proteins and identify Nhedc2, which is probably associated with proton transport in osteoclasts, as a regulator of osteoclast function.
ISSN
1615-9853
Language
English
URI
http://hdl.handle.net/10371/68971
DOI
https://doi.org/10.1002/pmic.200701192
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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