title: mTORC1 signaling controls mammalian skeletal growth through stimulation of protein synthesis.
abstract: Much of the mammalian skeleton is derived from a cartilage template that undergoes rapid growth during embryogenesis, but the molecular mechanism of growth regulation is not well understood. Signaling by mammalian target of rapamycin complex 1 (mTORC1) is an evolutionarily conserved mechanism that controls cellular growth. Here we report that mTORC1 signaling is activated during limb cartilage development in the mouse embryo. Disruption of mTORC1 signaling through deletion of either mTOR or the associated protein Raptor greatly diminishes embryonic skeletal growth associated with severe delays in chondrocyte hypertrophy and bone formation. The growth reduction of cartilage is not due to changes in chondrocyte proliferation or survival, but is caused by a reduction in cell size and in the amount of cartilage matrix. Metabolic labeling reveals a notable deficit in the rate of protein synthesis in Raptor-deficient chondrocytes. Thus, mTORC1 signaling controls limb skeletal growth through stimulation of protein synthesis in chondrocytes.
authors.affiliation: Department of Orthopaedic Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Jianquan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, Washington University School of Medicine, St Louis, MO 63110, USA Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA Department of Developmental Biology, Washington University School of Medicine, St Louis, MO 63110, USA longf@wudosis.wustl.edu.
authors.forename: Fanxin
authors.initials: F
authors.lastname: Long
mesh_terms: D000818:Animals; D001846:Bone Development; D001842:Bone and Bones / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D049109:Cell Proliferation; D048429:Cell Size; D002470:Cell Survival; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D006984:Hypertrophy; D008322:Mammals / Q000196:embryology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism*; D014176:Protein Biosynthesis; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: Cartilage; Chondrocyte; Mouse; Raptor; Rptor; mTOR; mTORC1