start-ver=1.4 cd-journal=joma no-vol=25 cd-vols= no-issue=18 article-no= start-page=4175 end-page=4186 dt-received= dt-revised= dt-accepted= dt-pub-year=2006 dt-pub=20060920 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Secretion of L-glutamate from osteoclasts through transcytosis en-subtitle= kn-subtitle= en-abstract= kn-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. en-copyright= kn-copyright= en-aut-name=MorimotoRiyo en-aut-sei=Morimoto en-aut-mei=Riyo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=UeharaShunsuke en-aut-sei=Uehara en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YatsushiroShouki en-aut-sei=Yatsushiro en-aut-mei=Shouki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=JugeNarinobu en-aut-sei=Juge en-aut-mei=Narinobu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HuaZhaolin en-aut-sei=Hua en-aut-mei=Zhaolin kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SenohShigenori en-aut-sei=Senoh en-aut-mei=Shigenori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=EchigoNoriko en-aut-sei=Echigo en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HayashiMitsuko en-aut-sei=Hayashi en-aut-mei=Mitsuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MizoguchiToshihide en-aut-sei=Mizoguchi en-aut-mei=Toshihide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NinomiyaTadashi en-aut-sei=Ninomiya en-aut-mei=Tadashi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=UdagawaNobuyuki en-aut-sei=Udagawa en-aut-mei=Nobuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=OmoteHiroshi en-aut-sei=Omote en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamamotoAkitsugu en-aut-sei=Yamamoto en-aut-mei=Akitsugu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=EdwardsRobert H en-aut-sei=Edwards en-aut-mei=Robert H kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=MoriyamaYoshinori en-aut-sei=Moriyama en-aut-mei=Yoshinori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= affil-num=1 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=2 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=3 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=4 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=5 en-affil= kn-affil=Departments of Neurology and Physiology, Graduate Programs in Neuroscience and Cell Biology, University of California San Francisco School of Medicine affil-num=6 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=7 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=8 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=9 en-affil= kn-affil=Institute for Oral Science, Matsumoto Dental University affil-num=10 en-affil= kn-affil=Institute for Oral Science, Matsumoto Dental University affil-num=11 en-affil= kn-affil=Department of Biochemistry, Matsumoto Dental University affil-num=12 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences affil-num=13 en-affil= kn-affil=Department of Cell Biology, Nagahama Institute of Bioscience and Technology affil-num=14 en-affil= kn-affil=Departments of Neurology and Physiology, Graduate Programs in Neuroscience and Cell Biology, University of California San Francisco School of Medicine affil-num=15 en-affil= kn-affil=Laboratory of Membrane Biochemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences en-keyword=osteoclast kn-keyword=osteoclast en-keyword=vesicular glutamate transporter kn-keyword=vesicular glutamate transporter en-keyword=transcytosis kn-keyword=transcytosis en-keyword=bone resorption kn-keyword=bone resorption END