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Here, we found that mTORC1 activity declined during osteoclast precursors differentiation in vitro and in vivo. We further targeted deletion of Raptor (mTORC1 key component) or Tsc1 (mTORC1 negative regulator) to constitutively inhibit or activate mTORC1 in osteoclast precursors (monocytes\/macrophages), using LyzM-cre mice. Osteoclastic formation was drastically increased in cultures of Raptor deficient bone marrow monocytes\/macrophages (BMMs), and Raptor-deficient mice displayed osteopenia with enhanced osteoclastogenesis. Conversely, BMMs lacking Tsc1 exhibited a severe defect in osteoclast-like differentiation and absorptive function, both of which were restored following rapamycin treatment. Importantly, expression of nuclear factor \u03ba-light-chain-enhancer of activated B cells (NF-\u03baB) and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), transcription factors that are essential for osteoclast differentiation was negatively regulated by mTORC1 in osteoclast lineages. These results provide evidence that mTORC1 plays as a critical role as an osteoclastic differentiation-limiting signal and suggest a potential drawback in treating bone loss\u2013related diseases with mTOR inhibitors clinically. \u00a9 2017 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.3172","type":"journal-article","created":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T12:44:03Z","timestamp":1495111443000},"page":"1829-1840","source":"Crossref","is-referenced-by-count":74,"title":["mTORC1 Inhibits NF-\u03baB\/NFATc1 Signaling and Prevents Osteoclast Precursor Differentiation, In Vitro and In Mice"],"prefix":"10.1093","volume":"32","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cell BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina"},{"name":"Academy of Orthopedics, Guangdong Province, The Third Affiliated HospitalSouthern Medical 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UniversityGuangzhouChina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daozhang","family":"Cai","sequence":"additional","affiliation":[{"name":"Academy of Orthopedics, Guangdong Province, The Third Affiliated HospitalSouthern Medical UniversityGuangzhouChina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhai","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Cell BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina"},{"name":"Academy of Orthopedics, Guangdong Province, The Third Affiliated HospitalSouthern Medical UniversityGuangzhouChina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mangmang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cell BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guozhi","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of BiochemistryRush University Medical CenterChicagoILUSA"},{"name":"Department of Biology and Shenzhen Key Laboratory of Cell MicroenvironmentSouth University of Science and Technology of ChinaShenzhenChina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Spine SurgeryThe Third Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cell BiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochun","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Cell 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