Abstract
Original language | Undefined |
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Pages (from-to) | 356-365 |
Journal | Journal of tissue engineering and regenerative medicine |
Volume | 4 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2010 |
Keywords
- parathyroid hormone
- IR-72586
- osteogenic differentiation
- GPCR ligands
- Human mesenchymal stem cells
- prostaglandin E2
- protein kinase A
Cite this
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Timing, rather than the concentration of cyclic AMP, correlates to osteogenic differentiation of human mesenchymal stem cells. / Siddappa, R.; Doorn, J.; Liu, J.; Langerwerf, Eli; Arends, Roel; van Blitterswijk, Clemens; de Boer, Jan.
In: Journal of tissue engineering and regenerative medicine, Vol. 4, No. 5, 2010, p. 356-365.Research output: Contribution to journal › Article › Academic
TY - JOUR
T1 - Timing, rather than the concentration of cyclic AMP, correlates to osteogenic differentiation of human mesenchymal stem cells
AU - Siddappa, R.
AU - Doorn, J.
AU - Liu, J.
AU - Langerwerf, Eli
AU - Arends, Roel
AU - van Blitterswijk, Clemens
AU - de Boer, Jan
PY - 2010
Y1 - 2010
N2 - Previously, we demonstrated that protein kinase A (PKA) activation using dibutyryl-cAMP in human mesenchymal stem cells (hMSCs) induces in vitro osteogenesis and bone formation in vivo. To further investigate the physiological role of PKA in hMSC osteogenesis, we tested a selection of G-protein-coupled receptor ligands which signal via intracellular cAMP production and PKA activation. Treatment of hMSCs with parathyroid hormone, parathyroid hormone-related peptide, melatonin, epinephrine, calcitonin or calcitonin gene-related peptide did not result in accumulation of cAMP or induction of alkaline phosphatase (ALP) expression. The only ligand that did induce cAMP, prostaglandin E2, even inhibited ALP expression and mineralization, suggesting that physiological levels of cAMP may inhibit osteogenesis. Furthermore, intermittent exposure of hMSCs to dibutyryl-cAMP inhibited ALP expression, whereas we did not observe an inhibitive effect at low dibutyryl-cAMP concentrations. Taken together, our results demonstrate that cAMP can either stimulate or inhibit osteogenesis in hMSCs, depending on the duration, rather than the strength, of the signal provided.
AB - Previously, we demonstrated that protein kinase A (PKA) activation using dibutyryl-cAMP in human mesenchymal stem cells (hMSCs) induces in vitro osteogenesis and bone formation in vivo. To further investigate the physiological role of PKA in hMSC osteogenesis, we tested a selection of G-protein-coupled receptor ligands which signal via intracellular cAMP production and PKA activation. Treatment of hMSCs with parathyroid hormone, parathyroid hormone-related peptide, melatonin, epinephrine, calcitonin or calcitonin gene-related peptide did not result in accumulation of cAMP or induction of alkaline phosphatase (ALP) expression. The only ligand that did induce cAMP, prostaglandin E2, even inhibited ALP expression and mineralization, suggesting that physiological levels of cAMP may inhibit osteogenesis. Furthermore, intermittent exposure of hMSCs to dibutyryl-cAMP inhibited ALP expression, whereas we did not observe an inhibitive effect at low dibutyryl-cAMP concentrations. Taken together, our results demonstrate that cAMP can either stimulate or inhibit osteogenesis in hMSCs, depending on the duration, rather than the strength, of the signal provided.
KW - parathyroid hormone
KW - IR-72586
KW - osteogenic differentiation
KW - GPCR ligands
KW - Human mesenchymal stem cells
KW - prostaglandin E2
KW - protein kinase A
U2 - 10.1002/term.246
DO - 10.1002/term.246
M3 - Article
VL - 4
SP - 356
EP - 365
JO - Journal of tissue engineering and regenerative medicine
JF - Journal of tissue engineering and regenerative medicine
SN - 1932-6254
IS - 5
ER -