Mechanical stretch induces osteogenesis through the alternative activation of macrophages
- 26 February 2021
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 236 (9), 6376-6390
- https://doi.org/10.1002/jcp.30312
Abstract
For reconstructive surgeons, critically skeletal damage represents a major challenge. Growing evidence indicate that bone repair is dynamically regulated by the mesenchymal stem cell (MSC)‐macrophage interaction. Mechanical strain plays a fundamental role in bone repair and regeneration by influencing MSCs differentiation. Recently, a few findings indicate that macrophages may be mechanically sensitive and their phenotype can be regulated, in part, by mechanical cues. However, how macrophages subjected mechanical stretch influence the osteogenic differentiation of MSCs remain unclear. Thus, the purpose of this study is to explore the effect of macrophages stimulated with mechanical stretch on MSCs osteogenesis. By using a coculture system, we discover that macrophages efficiently induce osteogenic differentiation of MSCs under specific stretch conditions. A synergy mechanism between M2 polarization and YAP/BMP2 axis are identified through molecular and genetic analyses. Macrophages are activated by cyclic stretch and polarized to M2 phenotype that produce anti‐inflammatory cytokines such as IL‐10 and TGF‐β to regulate the local inflammatory microenvironment. Furthermore, mechanical stretch induces YAP activation and nuclear translocation, subsequently regulates downstream BMP2 expression to facilitate MSCs osteogenesis. These findings not only advance our understanding of the complex influence among the mechanical strain, macrophage inflammatory response as well as the osteogenic differentiation of MSCs, but also reveal a control system from mechanical signals to chemical response then to cell behaviors during bone repair and regeneration.Funding Information
- National Natural Science Foundation of China (11532004, 31270990, 31600762)
This publication has 45 references indexed in Scilit:
- BMP2 and mechanical loading cooperatively regulate immediate early signalling events in the BMP pathwayBMC Biology, 2012
- Induction of Osteogenesis in Mesenchymal Stem Cells by Activated Monocytes/Macrophages Depends on Oncostatin M SignalingThe International Journal of Cell Cloning, 2012
- The determination of stem cell fate by 3D scaffold structures through the control of cell shapeBiomaterials, 2011
- Infection, Inflammation, and Bone Regeneration: a Paradoxical RelationshipJournal of Dental Research, 2011
- Differential Regulation of Protrusion and Polarity by PI(3)K during Neutrophil Motility in Live ZebrafishDevelopmental Cell, 2010
- Cytoskeleton-based forecasting of stem cell lineage fatesProceedings of the National Academy of Sciences of the United States of America, 2009
- A Comprehensive Analysis of the Dual Roles of BMPs in Regulating Adipogenic and Osteogenic Differentiation of Mesenchymal Progenitor CellsStem Cells and Development, 2009
- Mechanotransduction in vascular physiology and atherogenesisNature Reviews Molecular Cell Biology, 2009
- Exploring the full spectrum of macrophage activationNature Reviews Immunology, 2008
- Collagen synthesis by mesenchymal stem cells and aortic valve interstitial cells in response to mechanical stretchCardiovascular Research, 2006