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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 24hrs 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. - Highlights: •more » Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting secretome between osteocytes and osteoblasts.« less

Authors:
 [1];  [2];  [3];  [2];  [1];  [2];  [3];  [4];  [2];  [2];  [2]
  1. Tissue Engineering Research Group, Dept. of Anatomy, Royal College of Surgeons in Ireland (Ireland)
  2. (Ireland)
  3. (AMBER), Trinity College Dublin & Royal College of Surgeons in Ireland (Ireland)
  4. Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin (Ireland)
Publication Date:
OSTI Identifier:
22461980
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 459; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BONE CELLS; COMPARATIVE EVALUATIONS; FLUID FLOW; LOADING; MIGRATION; REGULATIONS; SKELETON; STEM CELLS

Citation Formats

Brady, Robert T., Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Advanced Materials and BioEngineering Research Centre, Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick, O'Brien, Fergal J., Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Advanced Materials and BioEngineering Research Centre, Hoey, David A., E-mail: david.hoey@ul.ie, Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick, The Centre for Applied Biomedical Engineering Research, University of Limerick, and Materials & Surface Science Institute, University of Limerick. Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation. United States: N. p., 2015. Web. doi:10.1016/J.BBRC.2015.02.080.
Brady, Robert T., Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Advanced Materials and BioEngineering Research Centre, Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick, O'Brien, Fergal J., Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Advanced Materials and BioEngineering Research Centre, Hoey, David A., E-mail: david.hoey@ul.ie, Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick, The Centre for Applied Biomedical Engineering Research, University of Limerick, & Materials & Surface Science Institute, University of Limerick. Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation. United States. doi:10.1016/J.BBRC.2015.02.080.
Brady, Robert T., Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Advanced Materials and BioEngineering Research Centre, Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick, O'Brien, Fergal J., Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin, Advanced Materials and BioEngineering Research Centre, Hoey, David A., E-mail: david.hoey@ul.ie, Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick, The Centre for Applied Biomedical Engineering Research, University of Limerick, and Materials & Surface Science Institute, University of Limerick. Fri . "Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation". United States. doi:10.1016/J.BBRC.2015.02.080.
@article{osti_22461980,
title = {Mechanically stimulated bone cells secrete paracrine factors that regulate osteoprogenitor recruitment, proliferation, and differentiation},
author = {Brady, Robert T. and Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin and Advanced Materials and BioEngineering Research Centre and Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick and O'Brien, Fergal J. and Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin and Advanced Materials and BioEngineering Research Centre and Hoey, David A., E-mail: david.hoey@ul.ie and Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick and The Centre for Applied Biomedical Engineering Research, University of Limerick and Materials & Surface Science Institute, University of Limerick},
abstractNote = {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 24hrs 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. - Highlights: • Physically stimulated osteocytes secrete factors that regulate osteoprogenitors. • These factors enhance recruitment, proliferation and osteogenic differentiation. • Physically stimulated osteoblasts secrete factors that also regulate progenitors. • These factors enhance recruitment but inhibit proliferation of osteoprogenitors. • This study highlights a contrasting secretome between osteocytes and osteoblasts.},
doi = {10.1016/J.BBRC.2015.02.080},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 459,
place = {United States},
year = {Fri Mar 27 00:00:00 EDT 2015},
month = {Fri Mar 27 00:00:00 EDT 2015}
}