このエントリーをはてなブックマークに追加
ID 34234
FullText URL
figs.pdf 2.84 MB
Author
Morimoto, Riyo
Uehara, Shunsuke
Yatsushiro, Shouki
Juge, Narinobu
Hua, Zhaolin
Senoh, Shigenori
Echigo, Noriko
Hayashi, Mitsuko
Mizoguchi, Toshihide
Ninomiya, Tadashi
Udagawa, Nobuyuki
Yamamoto, Akitsugu
Edwards, Robert H
Abstract
Osteoclasts are involved in the catabolism of the bone matrix and eliminate the resulting degradation products through transcytosis, but the molecular mechanism and regulation of transcytosis remain poorly understood. Upon differentiation, osteoclasts express vesicular glutamate transporter 1 (VGLUT1), which is essential for vesicular storage and subsequent exocytosis of glutamate in neurons. VGLUT1 is localized in transcytotic vesicles and accumulates L-glutamate. Osteoclasts secrete L-glutamate and the bone degradation products upon stimulation with KCl or ATP in a Ca2+-dependent manner. KCl- and ATP-dependent secretion of L-glutamate was absent in osteoclasts prepared from VGLUT1-/- knockout mice. Osteoclasts express mGluR8, a class III metabotropic glutamate receptor. Its stimulation by a specific agonist inhibits secretion of L-glutamate and bone degradation products, whereas its suppression by a specific antagonist stimulates bone resorption. Finally, it was found that VGLUT1-/- mice develop osteoporosis. Thus, in bone-resorbing osteoclasts, L-glutamate and bone degradation products are secreted through transcytosis and the released L-glutamate is involved in autoregulation of transcytosis. Glutamate signaling may play an important role in the bone homeostasis.
Keywords
osteoclast
vesicular glutamate transporter
transcytosis
bone resorption
Note
Digital Object Identifer:10.1038/sj.emboj.7601317
Published with permission from the copyright holder. This is the author's copy, as published in EMBO Journal, Sep 2006, Volume 25, Issue 18, Pages 4175-4186.
Publisher URL:http://dx.doi.org/10.1038/sj.emboj.7601317
Direct access to Thomson Web of Science record
Copyright © 2006 European Molecular Biology Organization
Published Date
2006-09-20
Publication Title
EMBO Journal
Volume
volume25
Issue
issue18
Publisher
European Molecular Biology Organization
Start Page
4175
End Page
4186
ISSN
0261-4189
NCID
AA10627582
Content Type
Journal Article
language
英語
Copyright Holders
European Molecular Biology Organization
File Version
author
Refereed
True
DOI
Submission Path
biochemistry/7