FAK Promotes Osteoblast Progenitor Cell Proliferation and Differentiation by Enhancing Wnt Signaling

ABSTRACT Decreased bone formation is often associated with increased bone marrow adiposity. The molecular mechanisms that are accountable for the negative correlation between bone mass and bone marrow adiposity are incompletely understood. Focal adhesion kinase (FAK) has critical functions in prolif...

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Bibliographic Details
Published in:Journal of bone and mineral research 2016-12, Vol.31 (12), p.2227-2238
Main Authors: Sun, Chunhui, Yuan, Hebao, Wang, Li, Wei, Xiaoxi, Williams, Linford, Krebsbach, Paul H, Guan, Jun‐Lin, Liu, Fei
Format: Article
Language:English
Subjects:
ADIPOCYTE
Adipogenesis
Animals
beta Catenin - metabolism
Bone Diseases, Metabolic - pathology
BONE MARROW
Bone Marrow Cells - cytology
Cell Differentiation
Cell Proliferation
FAK
Focal Adhesion Protein-Tyrosine Kinases - deficiency
Focal Adhesion Protein-Tyrosine Kinases - metabolism
Gene Deletion
Male
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - metabolism
Mice, Inbred C57BL
OSTEOBLASTS
Osteoblasts - cytology
Osteoblasts - metabolism
Osteogenesis
OSTEOPROGENITOR
Skull - cytology
Sp7 Transcription Factor - metabolism
Stem Cells - cytology
Stem Cells - metabolism
WNT
Wnt Signaling Pathway
β‐CATENIN
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Summary:ABSTRACT Decreased bone formation is often associated with increased bone marrow adiposity. The molecular mechanisms that are accountable for the negative correlation between bone mass and bone marrow adiposity are incompletely understood. Focal adhesion kinase (FAK) has critical functions in proliferation and differentiation of many cell types; however, its roles in osteoblast lineage cells are largely unknown. We show herein that mice lacking FAK in Osterix‐expressing cells exhibited decreased osteoblast number and low bone mass as well as increased bone marrow adiposity. The decreased bone mass in FAK‐deficient mice was accounted for by decreased proliferation, compromised osteogenic differentiation, and increased adipogenic differentiation of bone marrow Osterix‐expressing cells resulting from downregulation of Wnt/β‐catenin signaling due to the reduced expression of canonical Wnt ligands. In contrast, FAK loss in calvarial preosteoblasts had no adverse effect on their proliferation and osteogenic differentiation and these cells had intact Wnt/β‐catenin signaling. © 2016 American Society for Bone and Mineral Research.
ISSN:0884-0431
1523-4681
DOI:10.1002/jbmr.2908