title: mTORC1 Signaling Promotes Osteoblast Differentiation from Preosteoblasts.
abstract: Preosteoblasts are precursor cells that are committed to the osteoblast lineage. Differentiation of these cells to mature osteoblasts is regulated by the extracellular factors and environmental cues. Recent studies have implicated mTOR signaling in the regulation of osteoblast differentiation. However, mTOR exists in two distinct protein complexes (mTORC1 and mTORC2), and the specific role of mTORC1 in regulating the progression of preosteoblasts to mature osteoblastis still unclear. In this study, we first deleted Raptor, a unique and essential component of mTORC1, in primary calvarial cells. Deletion of Raptor resulted in loss of mTORC1 but an increase in mTORC2 signaling without overtly affecting autophagy. Under the osteogenic culture condition, Raptor-deficient cells exhibited a decrease in matrix synthesis and mineralization. qPCR analyses revealed that deletion of Raptor reduced the expression of late-stage markers for osteoblast differentiation (Bglap, Ibsp, and Col1a), while slightly increasing early osteoblast markers (Runx2, Sp7, and Alpl). Consistent with the findings in vitro, genetic ablation of Raptor in osterix-expressing cells led to osteopenia in mice. Together, our findings have identified a specific role for mTORC1 in the transition from preosteoblasts to mature osteoblasts.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; Orthopedic Institute, Soochow University, Suzhou, Jiangsu, China.
authors.forename: Jianquan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Orthopedic Surgery, Washington University, St. Louis, Missouri, United States of America; Department of Medicine, Washington University, St. Louis, Missouri, United States of America; Department of Developmental Biology, Washington University, St. Louis, Missouri, United States of America.
authors.forename: Fanxin
authors.initials: F
authors.lastname: Long
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002113:Calcification, Physiologic / Q000235:genetics; D002454:Cell Differentiation; D005109:Extracellular Matrix / Q000378:metabolism; D017353:Gene Deletion; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D046912:Multiprotein Complexes / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism*; D011859:Radiography; D000076223:Regulatory-Associated Protein of mTOR; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D046912:Multiprotein Complexes; D000076223:Regulatory-Associated Protein of mTOR; C540162:Rptor protein, mouse; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases