Journal Article

mTORC1 Signaling Promotes Osteoblast Differentiation from Preosteoblasts

Long, Fanxin, Chen, Jianquan

2015

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adaptor Proteins, Signal Transducing - genetics / Adenoviruses / Animals / Autophagy / Biocompatibility / Biomedical materials / Bone and Bones - diagnostic imaging / Bone and Bones - metabolism / Bone and Bones - pathology / Bone surgery / Calcification, Physiologic - genetics / Cbfa-1 protein / Cell culture / Cell death / Cell Differentiation / Clonal deletion / Differentiation / Enzymes / Extracellular Matrix - metabolism / Gene Deletion / Gene expression / Infections / Kinases / Laboratory animals / Markers / Mechanistic Target of Rapamycin Complex 1 / Mechanistic Target of Rapamycin Complex 2 / Mesenchymal Stromal Cells - cytology / Mesenchymal Stromal Cells - metabolism / Mice / Mice, Transgenic / Mineralization / Models, Animal / Multiprotein Complexes - metabolism / Osteoblastogenesis / Osteoblasts / Osteoblasts - cytology / Osteoblasts - metabolism / Osteopenia / Phagocytosis / Radiography / Regulatory-Associated Protein of mTOR / Signal Transduction / Signaling / Stem cells / Stem Cells - cytology / Stem Cells - metabolism / Studies / TOR protein / TOR Serine-Threonine Kinases - metabolism