{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T14:18:29Z","timestamp":1789395509703,"version":"build-2803163510"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T00:00:00Z","timestamp":1560384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H05131"],"award-info":[{"award-number":["16H05131"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17KT0051"],"award-info":[{"award-number":["17KT0051"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18H04971"],"award-info":[{"award-number":["18H04971"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17824969"],"award-info":[{"award-number":["17824969"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"DOI":"10.3389\/fphar.2019.00684","type":"journal-article","created":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T12:41:21Z","timestamp":1560429681000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["mTORC1 Activation in Osteoclasts Prevents Bone Loss in a Mouse Model of Osteoporosis"],"prefix":"10.3389","volume":"10","author":[{"given":"Manami","family":"Hiraiwa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kakeru","family":"Ozaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Iezaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyujin","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Fukasawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuhiro","family":"Horie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikari","family":"Kamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Tokumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Motono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyuki","family":"Kaneda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichi","family":"Hinoi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,6,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1038\/369756a0","article-title":"A mammalian protein targeted by G1-arresting rapamycin\u2013receptor complex","volume":"369","author":"Brown","year":"1994","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1002\/jbmr.2348","article-title":"mTORC2 signaling promotes skeletal growth and bone formation in mice","volume":"30","author":"Chen","year":"2015","journal-title":"J. Bone Miner. Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2848","DOI":"10.1242\/dev.108811","article-title":"mTORC1 signaling controls mammalian skeletal growth through stimulation of protein synthesis","volume":"141","author":"Chen","year":"2014","journal-title":"Development"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41413-017-0004-5","article-title":"mTOR signaling in skeletal development and disease","volume":"6","author":"Chen","year":"2018","journal-title":"Bone Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1074\/jbc.M116.764761","article-title":"Inactivation of regulatory-associated protein of mTOR (raptor)\/mammalian target of rapamycin complex 1 (mTORC1) signaling in osteoclasts increases bone mass by inhibiting osteoclast differentiation in mice","volume":"292","author":"Dai","year":"2017","journal-title":"J. Biol. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1146\/annurev-pathol-011110-130203","article-title":"Disorders of bone remodeling","volume":"6","author":"Feng","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"30918","DOI":"10.1038\/srep30918","article-title":"ATF3 controls proliferation of osteoclast precursor and bone remodeling","volume":"6","author":"Fukasawa","year":"2016","journal-title":"Sci. Rep."},{"key":"B8","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1016\/j.devcel.2006.10.007","article-title":"Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1","volume":"11","author":"Guertin","year":"2006","journal-title":"Dev. Cell."},{"key":"B9","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nature01660","article-title":"Control of osteoblast function and regulation of bone mass","volume":"423","author":"Harada","year":"2003","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.2353\/ajpath.2007.061039","article-title":"Glutamate suppresses osteoclastogenesis through the cystine\/glutamate antiporter","volume":"170","author":"Hinoi","year":"2007","journal-title":"Am. J. Pathol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/s42003-018-0028-4","article-title":"mTORC1 impedes osteoclast differentiation via calcineurin and NFATc1","volume":"1","author":"Huynh","year":"2018","journal-title":"Comm. Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.stemcr.2018.05.020","article-title":"Translational control of Sox9 RNA by mTORC1 Contributes to skeletogenesis","volume":"11","author":"Iezaki","year":"2018","journal-title":"Stem Cell. Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1002\/jbmr.2720","article-title":"The Transcriptional modulator interferon-related developmental regulator 1 in osteoblasts suppresses bone formation and promotes bone resorption","volume":"31","author":"Iezaki","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1038\/ncb1183","article-title":"Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive","volume":"6","author":"Jacinto","year":"2004","journal-title":"Nat. Cell. Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/nature11861","article-title":"mTOR is a key modulator of ageing and age-related disease","volume":"493","author":"Johnson","year":"2013","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1146\/annurev.cellbio.042308.113308","article-title":"Genetic control of bone formation","volume":"25","author":"Karsenty","year":"2009","journal-title":"Annu. Rev. Cell. Dev. Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/j.cub.2005.02.053","article-title":"Rheb binds and regulates the mTOR kinase","volume":"15","author":"Long","year":"2005","journal-title":"Curr. Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"6710","DOI":"10.1128\/MCB.24.15.6710-6718.2004","article-title":"mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells","volume":"24","author":"Murakami","year":"2004","journal-title":"Mol. Cell Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/j.bbadis.2013.03.010","article-title":"Repression of adipogenesis through promotion of Wnt\/beta-catenin signaling by TIS7 up-regulated in adipocytes under hypoxia","volume":"1832","author":"Nakamura","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"B20","doi-asserted-by":"publisher","first-page":"15461","DOI":"10.1074\/jbc.C200665200","article-title":"The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif","volume":"278","author":"Nojima","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"11818","DOI":"10.1073\/pnas.1716173114","article-title":"Twenty-five years of mTOR: uncovering the link from nutrients to growth","volume":"114","author":"Sabatini","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"B22","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/0092-8674(94)90570-3","article-title":"RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs","volume":"78","author":"Sabatini","year":"1994","journal-title":"Cell"},{"key":"B23","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.devcel.2006.08.013","article-title":"Multiallelic disruption of the rictor gene in mice reveals that mTOR complex 2 is essential for fetal growth and viability","volume":"11","author":"Shiota","year":"2006","journal-title":"Dev. Cell."},{"key":"B24","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1038\/nrg1122","article-title":"Genetic regulation of osteoclast development and function","volume":"4","author":"Teitelbaum","year":"2003","journal-title":"Nat. Rev. Genet."},{"key":"B25","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3389\/fcell.2017.00054","article-title":"Regulation of osteoclast growth and fusion by mTOR\/raptor and mTOR\/rictor\/Akt","volume":"5","author":"Tiedemann","year":"2017","journal-title":"Front. Cell. Dev. Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1359\/jbmr.090217","article-title":"Evaluation of pharmaceuticals with a novel 50-hour animal model of bone loss","volume":"24","author":"Tomimori","year":"2009","journal-title":"J. Bone Miner. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"24553","DOI":"10.1074\/jbc.M600939200","article-title":"Glutamate inhibits chondral mineralization through apoptotic cell death mediated by retrograde operation of the cystine\/glutamate antiporter","volume":"281","author":"Wang","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1111\/j.1476-5381.2012.01856.x","article-title":"The natural polyamines spermidine and spermine prevent bone loss through preferential disruption of osteoclastic activation in ovariectomized mice","volume":"166","author":"Yamamoto","year":"2012","journal-title":"Br J. Pharmacol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"11151","DOI":"10.1038\/ncomms11151","article-title":"mTORC1 regulates PTHrP to coordinate chondrocyte growth, proliferation and differentiation","volume":"7","author":"Yan","year":"2016","journal-title":"Nat. Commun."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1002\/jbmr.3172","article-title":"mTORC1 inhibits NF-kappaB\/NFATc1 signaling and prevents osteoclast precursor differentiation, in vitro and in mice","volume":"32","author":"Zhang","year":"2017","journal-title":"J. Bone Miner. Res."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2019.00684\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T12:41:23Z","timestamp":1560429683000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2019.00684\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,13]]},"references-count":30,"alternative-id":["10.3389\/fphar.2019.00684"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2019.00684","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,13]]},"article-number":"684"}}