دورية أكاديمية
أعرض في EDS

mTORC1 Plays an Important Role in Skeletal Development by Controlling Preosteoblast Differentiation.

التفاصيل البيبلوغرافية
العنوان: mTORC1 Plays an Important Role in Skeletal Development by Controlling Preosteoblast Differentiation.
المؤلفون: Fitter S; Myeloma Research Laboratory, Adelaide Medical School, Faculty of Health and Medical Science, University of Adelaide, Adelaide, Australia stephen.fitter@adelaide.edu.au.; Cancer Theme, South Australian Health and Medical Research Institute, Adelaide, Australia., Matthews MP; Myeloma Research Laboratory, Adelaide Medical School, Faculty of Health and Medical Science, University of Adelaide, Adelaide, Australia., Martin SK; Myeloma Research Laboratory, Adelaide Medical School, Faculty of Health and Medical Science, University of Adelaide, Adelaide, Australia.; Cancer Theme, South Australian Health and Medical Research Institute, Adelaide, Australia., Xie J; Nutrition and Metabolism, South Australian Health and Medical Research Institute, Adelaide, Australia., Ooi SS; Myeloma Research Laboratory, Adelaide Medical School, Faculty of Health and Medical Science, University of Adelaide, Adelaide, Australia.; Cancer Theme, South Australian Health and Medical Research Institute, Adelaide, Australia., Walkley CR; Stem Cell Regulation Unit, St Vincent's Institute of Medical Research, Melbourne, Victoria, Australia., Codrington JD; School of Mechanical Engineering, University of Adelaide, Adelaide, Australia., Ruegg MA; Biozentrum, University of Basel, Basel, Switzerland., Hall MN; Biozentrum, University of Basel, Basel, Switzerland., Proud CG; Nutrition and Metabolism, South Australian Health and Medical Research Institute, Adelaide, Australia.; School of Biological Sciences, University of Adelaide, Adelaide, Australia.; Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China., Gronthos S; Mesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, Australia.; Cancer Theme, South Australian Health and Medical Research Institute, Adelaide, Australia., Zannettino ACW; Myeloma Research Laboratory, Adelaide Medical School, Faculty of Health and Medical Science, University of Adelaide, Adelaide, Australia.; Cancer Theme, South Australian Health and Medical Research Institute, Adelaide, Australia.
المصدر: Molecular and cellular biology [Mol Cell Biol] 2017 Mar 17; Vol. 37 (7). Date of Electronic Publication: 2017 Mar 17 (Print Publication: 2017).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Taylor & Francis Country of Publication: United States NLM ID: 8109087 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1098-5549 (Electronic) Linking ISSN: 02707306 NLM ISO Abbreviation: Mol Cell Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2023- : [Philadelphia] : Taylor & Francis
Original Publication: [Washington, D.C.] : American Society for Microbiology, [c1981-
مواضيع طبية MeSH: Bone Development* , Cell Differentiation*, Multiprotein Complexes/*metabolism , Osteoblasts/*cytology , Osteoblasts/*metabolism , TOR Serine-Threonine Kinases/*metabolism, Adaptor Proteins, Signal Transducing/metabolism ; Adipose Tissue/metabolism ; Animals ; Animals, Newborn ; Gene Deletion ; Growth Plate/metabolism ; Mechanistic Target of Rapamycin Complex 1 ; Mice, Transgenic ; Organ Size ; Phenotype ; Regulatory-Associated Protein of mTOR ; Transcription, Genetic
مستخلص: The mammalian target of rapamycin complex 1 (mTORC1) is activated by extracellular factors that control bone accrual. However, the direct role of this complex in osteoblast biology remains to be determined. To investigate this question, we disrupted mTORC1 function in preosteoblasts by targeted deletion of Raptor ( Rptor ) in Osterix -expressing cells. Deletion of Rptor resulted in reduced limb length that was associated with smaller epiphyseal growth plates in the postnatal skeleton. Rptor deletion caused a marked reduction in pre- and postnatal bone accrual, which was evident in skeletal elements derived from both intramembranous and endochondrial ossification. The decrease in bone accrual, as well as the associated increase in skeletal fragility, was due to a reduction in osteoblast function. In vitro , osteoblasts derived from knockout mice display a reduced osteogenic potential, and an assessment of bone-developmental markers in Rptor knockout osteoblasts revealed a transcriptional profile consistent with an immature osteoblast phenotype suggesting that osteoblast differentiation was stalled early in osteogenesis. Metabolic labeling and an assessment of cell size of Rptor knockout osteoblasts revealed a significant decrease in protein synthesis, a major driver of cell growth. These findings demonstrate that mTORC1 plays an important role in skeletal development by regulating mRNA translation during preosteoblast differentiation.
(Copyright © 2017 American Society for Microbiology.)
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فهرسة مساهمة: Keywords: Raptor; mTORC1; osteoblast; osteogenesis
المشرفين على المادة: 0 (Adaptor Proteins, Signal Transducing)
0 (Multiprotein Complexes)
0 (Regulatory-Associated Protein of mTOR)
0 (Rptor protein, mouse)
EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
تواريخ الأحداث: Date Created: 20170111 Date Completed: 20170630 Latest Revision: 20211204
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5359426
DOI: 10.1128/MCB.00668-16
PMID: 28069737
قاعدة البيانات: MEDLINE
الوصف
تدمد:1098-5549
DOI:10.1128/MCB.00668-16