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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sun, Dahui Junger, Wolfgang G. Yuan, Changji Zhang, Wenyan Bao, Yi Qin, Daming Wang, Chengxue Tan, Lei Qi, Baochang Zhu, Dong Zhang, Xizheng Yu, Tiecheng |
| Description | Author Affiliation: Sun D ( Department of Orthopedics, The First Norman Bethune Hospital of Jilin University, Changchun, People's Republic of China.) |
| Abstract | 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. |
| File Format | HTM / HTML |
| ISSN | 10665099 |
| e-ISSN | 15494918 |
| DOI | 10.1002/stem.1356 |
| Journal | STEM CELLS |
| Issue Number | 6 |
| Volume Number | 31 |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2013-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Cell Biology Discipline Embryology Adenosine Triphosphate Metabolism Lithotripsy Mesenchymal Stromal Cells Cytology Receptors, Purinergic P2x7 Alkaline Phosphatase Genetics Apyrase Bone Marrow Physiology Calcium Cell Differentiation Cells, Cultured Enzymology Osteocalcin Osteogenesis Proto-oncogene Proteins C-fos Proto-oncogene Proteins C-jun Rna, Messenger Signal Transduction P38 Mitogen-activated Protein Kinases Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Developmental Biology Medicine Molecular Medicine |
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