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

Ramakrishnaiah Siddappa, Anton Martens, Joyce Doorn, Anouk Leusink, Cristina Olivo, Ruud Licht, Linda van Rijn, Claudia Gaspar, Riccardo Fodde, Frank Janssen, Clemens van Blitterswijk, Jan de Boer

Research output: Contribution to journalArticleAcademicpeer-review

171 Citations (Scopus)
114 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)7281-7286
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number20
DOIs
Publication statusPublished - 2008

Keywords

  • METIS-253659
  • IR-60305

Fingerprint Dive into the research topics of 'cAMP/PKA pathway activation in human mesenchymal stem cells in vitro results in robust bone formation in vivo'. Together they form a unique fingerprint.

  • Cite this