title: The role of focal adhesion kinase in BMP4 induction of mesenchymal stem cell adipogenesis.
abstract: Obesity is characterized by excessive adipocytic number growth and resultant adipose tissue hyperplasia. However, molecular mechanisms of abnormal recruitment of new adipocytes from precursor cells are not fully known. Several studies showed that bone morphogenetic proteins (BMPs) also play a role in inducing mesenchymal stem cells (MSCs) to commit to adipocytes. We tested the hypothesis that focal adhesion kinase (FAK), one of the vital focal adhesion signaling molecules, is required for BMP4 induction of MSC adipogenesis. BMP4 exposure triggered FAK activation at pY397 auto-phosphorylation site in murine C3H10T1/2 MSCs. Interestingly, silencing FAK by small hairpin RNA (shRNA) significantly suppressed BMP4 induction of MSC adipogenic activities, including lipid accumulation and expression of key adipogenic genes (C/EBPα, PPARγ, aP2), as relative to shRNA vector control. As a potential molecular mechanism, BMP4-triggered phosphorylation in Smad1/5/8 and p38 was significantly downregulated by shRNA-FAK. Pharmacological FAK inhibitor 14 provided similar results in BMP4-mediated MSC adipogenesis and Smad/p38 signaling. Our data clearly suggest a link between FAK and BMP4 induction of MSC adipogenesis, and may indicate a potential therapeutic approach targeting FAK for dealing with obesity.
authors.affiliation: Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE 68588, USA.
authors.forename: Jeong Soon
authors.initials: JS
authors.lastname: Lee
authors.forename: Ligyeom
authors.initials: L
authors.lastname: Ha
authors.forename: Il Keun
authors.initials: IK
authors.lastname: Kwon
authors.forename: Jung Yul
authors.initials: JY
authors.lastname: Lim
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology*; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D051416:Focal Adhesion Protein-Tyrosine Kinases