title: 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 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.
authors.affiliation: Department of Biologic and Materials Sciences and Division of Prosthodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA.|Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Biologic and Materials Sciences and Division of Prosthodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Hebao
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Biologic and Materials Sciences and Division of Prosthodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biologic and Materials Sciences and Division of Prosthodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA.|Department of Orthodontics, Jilin University School and Hospital of Stomatology, Changchun, Jilin, China.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Biologic and Materials Sciences and Division of Prosthodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Linford
authors.initials: L
authors.lastname: Williams
authors.affiliation: Department of Biologic and Materials Sciences and Division of Prosthodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Krebsbach
authors.affiliation: Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Jun-Lin
authors.initials: JL
authors.lastname: Guan
authors.affiliation: Department of Biologic and Materials Sciences and Division of Prosthodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
mesh_terms: D050156:Adipogenesis; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000172:deficiency / Q000378:metabolism*; D017353:Gene Deletion; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D012886:Skull / Q000166:cytology; D000076182:Sp7 Transcription Factor / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D051176:beta Catenin; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: ADIPOCYTE; BONE MARROW; FAK; OSTEOBLASTS; OSTEOPROGENITOR; WNT; β-CATENIN