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In the current study, we generated TamCartSirt1\u2212\/\u2212 [Sirt1 conditional knockout (cKO)] mice to explore the role of Sirt1 during postnatal endochondral ossification. Compared with control mice, cKO mice exhibited growth retardation associated with inhibited chondrocyte proliferation and hypertrophy, as well as activated apoptosis. These effects were regulated by hyperactivation of mammalian target of rapamycin complex 1 (mTORC1) signaling, and thereby inhibition of autophagy and induction of endoplasmic reticulum stress in growth plate chondrocytes. IP injection of the mTORC1 inhibitor rapamycin to mice with Sirt1 deletion partially neutralized such inhibitory effects of Sirt1 ablation on longitudinal bone growth, indicating the causative link between SIRT1 and mTORC1 signaling in the growth plate. Mechanistically, SIRT1 interacted with tuberous sclerosis complex 2 (TSC2), a key upstream negative regulator of mTORC1 signaling, and loss of Sirt1 inhibited TSC2 expression, resulting in hyperactivated mTORC1 signaling in chondrocytes. In conclusion, our findings suggest that loss of Sirt1 may trigger mTORC1 signaling in growth plate chondrocytes and contributes to growth retardation, thus indicating that SIRT1 is an important regulator during chondrogenesis and providing new insights into the clinical potential of SIRT1 in bone development.<\/jats:p>","DOI":"10.1210\/en.2019-00427","type":"journal-article","created":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T14:40:52Z","timestamp":1571928052000},"page":"3001-3017","source":"Crossref","is-referenced-by-count":18,"title":["Cartilage Ablation of Sirt1 Causes Inhibition of Growth Plate Chondrogenesis by Hyperactivation of mTORC1 Signaling"],"prefix":"10.1210","volume":"160","author":[{"given":"Xinxin","family":"Jin","sequence":"first","affiliation":[{"name":"Center for Translational Medicine, The First Affiliated Hospital of Xi\u2019an Jiaotong University School of Medicine, Xi\u2019an, Shaanxi, People\u2019s Republic of 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