RRC ID 51848
Author Jiang M, Fu X, Yang H, Long F, Chen J.
Title mTORC1 Signaling Promotes Limb Bud Cell Growth and Chondrogenesis.
Journal J Cell Biochem
Abstract mTORC1 signaling has been shown to promote limb skeletal growth through stimulation of protein synthesis in chondrocytes. However, potential roles of mTORC1 in prechondrogenic mesenchyme have not been explored. In this study, we first deleted Raptor, a unique and essential component of mTORC1, in prechondrogenic limb mesenchymal cells. Deletion of Raptor reduced the size of limb bud cells, resulting in overall diminution of the limb bud without affecting skeletal patterning. We then examined the potential role of mTORC1 in chondrogenic differentiation in vitro. Both pharmacological and genetic disruption of mTORC1 significantly suppressed the number and size of cartilage nodules in micromass cultures of limb bud mesenchymal cells. Similarly, inhibition of mTORC1 signaling in chondrogenic ATDC5 cells greatly impaired cartilage nodule formation, and decreased the expression of the master transcriptional factor Sox9, along with the cartilage matrix genes Acan and Col2a1. Thus, we have identified an important role for mTORC1 signaling in promoting limb mesenchymal cell growth and chondrogenesis during embryonic development. J. Cell. Biochem. 118: 748-753, 2017. © 2016 Wiley Periodicals, Inc.
Volume 118(4)
Pages 748-753
Published 2017-4-1
DOI 10.1002/jcb.25728
PMID 27606668
PMC PMC5296292
MeSH Adaptor Proteins, Signal Transducing / deficiency Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / physiology* Animals Cells, Cultured Chondrocytes / cytology Chondrocytes / drug effects Chondrocytes / physiology Chondrogenesis / drug effects Chondrogenesis / genetics Chondrogenesis / physiology* Embryonic Stem Cells / cytology Embryonic Stem Cells / physiology Female Limb Buds / cytology Limb Buds / embryology* Limb Buds / physiology Mechanistic Target of Rapamycin Complex 1 Mesenchymal Stem Cells / cytology Mesenchymal Stem Cells / physiology Mice Mice, Knockout Multiprotein Complexes / deficiency Multiprotein Complexes / genetics Multiprotein Complexes / physiology* Pregnancy Regulatory-Associated Protein of mTOR Signal Transduction Sirolimus / pharmacology TOR Serine-Threonine Kinases / deficiency TOR Serine-Threonine Kinases / genetics TOR Serine-Threonine Kinases / physiology*
IF 3.448
Times Cited 8
Human and Animal Cells ATDC5(RCB0565)