title: Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism.
abstract: It has long been suspected, but never directly shown, that bone formed to accommodate an increase in mechanical loading is related to the creation of osteoblasts from skeletal stem cells. Indeed, biophysical stimuli potently regulate osteogenic lineage commitmentin vitro In this study, we transplanted bone marrow cells expressing green fluorescent protein, to enable lineage tracing, and subjected mice to a biophysical stimulus, to elicit a bone-forming response. We detected cells derived from transplanted progenitors embedded within the bone matrix near active bone-forming surfaces in response to loading, demonstrating for the first time, that mechanical signals enhance the homing and attachment of bone marrow cells to bone surfaces and the commitment to an osteogenic lineage of these cellsin vivo Furthermore, we used an inducible Cre/Lox recombination system to delete kinesin family member 3A (Kif3a), a gene that is essential for primary cilia formation, at will in transplanted cells and their progeny, regardless of which tissue may have incorporated them. Disruption of the mechanosensing organelle, the primary cilium in a progenitor population, significantly decreased the amount of bone formed in response to mechanical stimulation. The collective results of our study directly demonstrate that, in a novel experimental stem cell mechanobiology model, mechanical signals enhance osteogenic lineage commitmentin vivoand that the primary cilium contributes to this process.-Chen, J. C., Hoey, D. A., Chua, M., Bellon, R., Jacobs, C. R. Mechanical signals promote osteogenic fate through a primary cilia-mediated mechanism.
authors.affiliation: *Department of Biomedical Engineering and Department of Chemical Engineering, Columbia University, New York, New York, USA; Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, and Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland; Department of Mechanical, Aeronautical, and Biomedical Engineering, Centre for Applied Biomedical Engineering Research, Materials and Surface Science Institute, University of Limerick, Limerick, Ireland; and Department of Biotechnology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Chen
authors.affiliation: *Department of Biomedical Engineering and Department of Chemical Engineering, Columbia University, New York, New York, USA; Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, and Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland; Department of Mechanical, Aeronautical, and Biomedical Engineering, Centre for Applied Biomedical Engineering Research, Materials and Surface Science Institute, University of Limerick, Limerick, Ireland; and Department of Biotechnology, University of British Columbia, Vancouver, British Columbia, Canada david.hoey@ul.ie.
authors.forename: David A
authors.initials: DA
authors.lastname: Hoey
authors.affiliation: *Department of Biomedical Engineering and Department of Chemical Engineering, Columbia University, New York, New York, USA; Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, and Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland; Department of Mechanical, Aeronautical, and Biomedical Engineering, Centre for Applied Biomedical Engineering Research, Materials and Surface Science Institute, University of Limerick, Limerick, Ireland; and Department of Biotechnology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Mardonn
authors.initials: M
authors.lastname: Chua
authors.affiliation: *Department of Biomedical Engineering and Department of Chemical Engineering, Columbia University, New York, New York, USA; Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, and Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland; Department of Mechanical, Aeronautical, and Biomedical Engineering, Centre for Applied Biomedical Engineering Research, Materials and Surface Science Institute, University of Limerick, Limerick, Ireland; and Department of Biotechnology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Raymond
authors.initials: R
authors.lastname: Bellon
authors.affiliation: *Department of Biomedical Engineering and Department of Chemical Engineering, Columbia University, New York, New York, USA; Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, and Department of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland; Department of Mechanical, Aeronautical, and Biomedical Engineering, Centre for Applied Biomedical Engineering Research, Materials and Surface Science Institute, University of Limerick, Limerick, Ireland; and Department of Biotechnology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods; D002478:Cells, Cultured; D002923:Cilia / Q000502:physiology*; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D013314:Stress, Mechanical
chemical_list: C490202:Kif3a protein, mouse; D049452:Green Fluorescent Proteins; D016547:Kinesins
keywords: bone; homing; mesenchymal stem cell; primary cilium; ulna loading