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Tissue-Specific Stem Cells
Article first published online: 22 MAY 2013
Copyright © 2013 AlphaMed Press
Volume 31, Issue 6, pages 1170–1180, June 2013
How to Cite
Sun, D., Junger, W. G., Yuan, C., Zhang, W., Bao, Y., Qin, D., Wang, C., Tan, L., Qi, B., Zhu, D., Zhang, X. and Yu, T. (2013), Shockwaves Induce Osteogenic Differentiation of Human Mesenchymal Stem Cells Through ATP Release and Activation of P2X7 Receptors. STEM CELLS, 31: 1170–1180. doi: 10.1002/stem.1356
Author contributions: D.S.: performed experiments and wrote the manuscript; W.G.J.: helped with study design and finalizing manuscript; C.Y.: provided administrative support; W.Z.: provided study material; Y.B.: prepared figures; D.Q. and C.W.: prepared samples; L.T. and B.Q.: performed experiments and collected data; D.Z. and X.Z.: provided administrative support; T.Y.: Developed concept, designed the study, provided overall guidance, and finalized manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
first published online in STEM CELLS EXPRESS February 13, 2013.
- Issue published online: 22 MAY 2013
- Article first published online: 22 MAY 2013
- Accepted manuscript online: 13 FEB 2013 06:18AM EST
- Manuscript Accepted: 29 JAN 2013
- Manuscript Revised: 13 JAN 2013
- Manuscript Received: 16 OCT 2012
- National Natural Science Foundation of China. Grant Numbers: 81172183, 30500132, 31270202, 10832012, 11272134
- Human mesenchymal stem cells;
- Osteogenic differentiation;
- p38 MAPK;
Shockwave treatment promotes bone healing of nonunion fractures. In this study, we investigated whether this effect could be due to adenosine 5′-triphosphate (ATP) release-induced differentiation of human mesenchymal stem cells (hMSCs) into osteoprogenitor cells. Cultured bone marrow-derived hMSCs were subjected to shockwave treatment and ATP release was assessed. Osteogenic differentiation and mineralization of hMSCs were evaluated by examining alkaline phosphatase activity, osteocalcin production, and calcium nodule formation. Expression of P2X7 receptors and c-fos and c-jun mRNA was determined with real-time reverse transcription polymerase chain reaction and Western blotting. P2X7-siRNA, apyrase, P2 receptor antagonists, and p38 MAPK inhibitors were used to evaluate the roles of ATP release, P2X7 receptors, and p38 MAPK signaling in shockwave-induced osteogenic hMSCs differentiation. Shockwave treatment released significant amounts (∼7 μM) of ATP from hMSCs. Shockwaves and exogenous ATP induced c-fos and c-jun mRNA transcription, p38 MAPK activation, and hMSC differentiation. Removal of ATP with apyrase, targeting of P2X7 receptors with P2X7-siRNA or selective antagonists, or blockade of p38 MAPK with SB203580 prevented osteogenic differentiation of hMSCs. Our findings indicate that shockwaves release cellular ATP that activates P2X7 receptors and downstream signaling events that caused osteogenic differentiation of hMSCs. We conclude that shockwave therapy promotes bone healing through P2X7 receptor signaling, which contributes to hMSC differentiation. STEM Cells 2013;31:1170–1180