cAMP/PKA pathway activation in human mesenchymal stem cells in vitro results in robust bone formation in vivo

Share/Save/Bookmark

Siddappa, Ramakrishnaiah and Martens, Anton and Doorn, Joyce and Leusink, Anouk and Olivo, Cristina and Licht, Ruud and Rijn van, Linda and Gaspar, Claudia and Fodde, Riccardo and Janssen, Frank and Blitterswijk van, Clemens and Boer de, Jan (2008) cAMP/PKA pathway activation in human mesenchymal stem cells in vitro results in robust bone formation in vivo. Proceedings of the National Academy of Sciences of the United States of America, PNAS, 105 (20). pp. 7281-7286. ISSN 0027-8424

[img]
Preview
PDF (Article)
682Kb
[img]PDF (Supporting Information)
Restricted to UT campus only
: Request a copy
2043Kb
Abstract:Tissue engineering of large bone defects is approached through implantation of autologous osteogenic cells, generally referred to as multipotent stromal cells or mesenchymal stem cells (MSCs). Animal-derived MSCs successfully bridge large bone defects, but models for ectopic bone formation as well as recent clinical trials demonstrate that bone formation by human MSCs (hMSCs) is inadequate. The expansion phase presents an attractive window to direct hMSCs by pharmacological manipulation, even though no profound effect on bone formation in vivo has been described so far using this approach. We report that activation of protein kinase A elicits an immediate response through induction of genes such as ID2 and FosB, followed by sustained secretion of bone-related cytokines such as BMP-2, IGF-1, and IL-11. As a consequence, PKA activation results in robust in vivo bone formation by hMSCs derived from orthopedic patients.
Item Type:Article
Copyright:© 2008 National Academy of Sciences of the United States of America
Faculty:
Science and Technology (TNW)
Research Group:
Link to this item:http://purl.utwente.nl/publications/60305
Official URL:http://dx.doi.org/10.1073/pnas.0711190105
Export this item as:BibTeX
EndNote
HTML Citation
Reference Manager

 

Repository Staff Only: item control page

Metis ID: 253659