title: Sprouty 2, an Early Response Gene Regulator of FosB and Mesenchymal Stem Cell Proliferation During Mechanical Loading and Osteogenic Differentiation.
abstract: Sprouty 2 (Spry2), an inhibitor of MAP kinase signaling was previously shown by our group to be induced during mechanical loading of mesenchymal stem cells (MSCs). Here, we studied the implication of Spry2 activation during mechanical loading and chemically induced MSC differentiation. Spry 2 expression showed an immediate early response during mechanical loading and chemical induction of osteogenic differentiation and followed the same pattern as osteogenic associated gene FosB and was necessary for the induction of FosB, as Spry 2 knock down also abrogated the upregulation of FosB expression. Spry 2 knock down was, also associated with an early response of the osteogenic genes Runx-2 and ALP. Neither the knock-down of Spry 2 nor the subsequent reduction in FosB had any effect on mid-late osteogenesis or mineralization but was associated with a significant increase in proliferation of MSC. These effects were possibly governed by negative regulation of MEK/Erk signaling as Spry 2 knock down resulted in an increase in phosphorylation of Erk1/2. In summary, our results shows the involvement of Spry2 in regulation of FosB and Runx2 genes, MAPK signaling and proliferation of MSC. Taken together these results suggest a possible role for Spry2 in regulation of MSC functions in response to mechanical loading and osteogenic differentiation. J. Cell. Biochem. 118: 2606-2614, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Division of Tissue Engineering and Biophotonics, Dental Institute, King's College London, Tower Wing, Guy's Hospital, London, SE1 9RT, UK.
authors.forename: A Kristin
authors.initials: AK
authors.lastname: Schneider
authors.affiliation: Division of Tissue Engineering and Biophotonics, Dental Institute, King's College London, Tower Wing, Guy's Hospital, London, SE1 9RT, UK.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cama
authors.affiliation: Division of Tissue Engineering and Biophotonics, Dental Institute, King's College London, Tower Wing, Guy's Hospital, London, SE1 9RT, UK.
authors.forename: Mandeep
authors.initials: M
authors.lastname: Ghuman
authors.affiliation: Division of Tissue Engineering and Biophotonics, Dental Institute, King's College London, Tower Wing, Guy's Hospital, London, SE1 9RT, UK.
authors.forename: Francis J
authors.identifier: 0000-0001-9073-8962
authors.initials: FJ
authors.lastname: Hughes
authors.affiliation: Division of Tissue Engineering and Biophotonics, Dental Institute, King's College London, Tower Wing, Guy's Hospital, London, SE1 9RT, UK.
authors.forename: Borzo
authors.initials: B
authors.lastname: Gharibi
mesh_terms: D002454:Cell Differentiation; D049109:Cell Proliferation; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis; D010766:Phosphorylation / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C064269:FOSB protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016760:Proto-Oncogene Proteins c-fos; C493709:RUNX2 protein, human; C485561:SPRY2 protein, human; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: DIFFERENTIATION; FosB; MECHANICAL LOADING; MESENCHYMAL STEM CELL; PROLIFERATION; Sprouty2