title: Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation.
abstract: Bone formation requires the recruitment, proliferation and osteogenic differentiation of mesenchymal progenitors. A potent stimulus driving this process is mechanical loading, yet the signalling mechanisms underpinning this are incompletely understood. The objective of this study was to investigate the role of the mechanically-stimulated osteocyte and osteoblast secretome in coordinating progenitor contributions to bone formation. Initially osteocytes (MLO-Y4) and osteoblasts (MC3T3) were mechanically stimulated for 24 hrs and secreted factors within the conditioned media were collected and used to evaluate mesenchymal stem cell (MSC) and osteoblast recruitment, proliferation and osteogenesis. Paracrine factors secreted by mechanically stimulated osteocytes significantly enhanced MSC migration, proliferation and osteogenesis and furthermore significantly increased osteoblast migration and proliferation when compared to factors secreted by statically cultured osteocytes. Secondly, paracrine factors secreted by mechanically stimulated osteoblasts significantly enhanced MSC migration but surprisingly, in contrast to the osteocyte secretome, inhibited MSC proliferation when compared to factors secreted by statically cultured osteoblasts. A similar trend was observed in osteoblasts. This study provides new information on mechanically driven signalling mechanisms in bone and highlights a contrasting secretome between cells at different stages in the bone lineage, furthering our understanding of loading-induced bone formation and indirect biophysical regulation of osteoprogenitors.
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, Ireland; Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Ireland; Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland, Ireland; Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick, Ireland.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Brady
authors.affiliation: Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland, Ireland; Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Ireland; Advanced Materials and BioEngineering Research Centre (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland, Ireland.
authors.forename: Fergal J
authors.initials: FJ
authors.lastname: O'Brien
authors.affiliation: Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Ireland; Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick, Ireland; The Centre for Applied Biomedical Engineering Research, University of Limerick, Ireland; Materials & Surface Science Institute, University of Limerick, Ireland. Electronic address: david.hoey@ul.ie.
authors.forename: David A
authors.initials: DA
authors.lastname: Hoey
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002633:Chemotaxis; D017077:Culture Media, Conditioned / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology*; D010011:Osteocytes / Q000166:cytology / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects; D010812:Physical Stimulation
chemical_list: D017077:Culture Media, Conditioned
keywords: Differentiation; Fluid flow; Mesenchymal stem cell; Migration; Osteocyte; Paracrine signalling