EMD273316 & EMD95833, type 4 phosphodiesterase inhibitors, stimulate fibroblastic-colony formation by bone marrow cells via direct inhibition of PDE4 and the induction of endogenous prostaglandin synthesis

BMC Pharmacology
Andrew ScuttClaus Fittschen

Abstract

Type 4 phosphodiesterase (PDE4) inhibitors have been shown to stimulate bone formation in vivo and to stimulate osteoblastic differentiation in vitro. As one possible mechanism for the stimulation of bone formation is the recruitment of osteoprogenitor cells from the bone marrow, we have investigated the effect of the PDE4 inhibitors EMD273316, EMD95833, EMD249615 and EMD 219906 on fibroblastic colony formation by whole bone marrow cells and on the ability of these colonies to adopt an osteoblastic phenotype. All four agents stimulated colony formation in a concentration dependent manner, however, in the case of EMD273316 & EMD95833, the effect was evident at lower concentrations and the addition of prostaglandin E2 (PGE2) was not necessary for maximal stimulation. It was subsequently found that co-incubation with indomethacin reduced the stimulatory effects of EMD273316 & EMD95833 but had no effect on the actions of EMD249615 and EMD 219906 and that EMD273316 & EMD95833 stimulated the synthesis of endogenous PGE2 by whole bone marrow cells whereas EMD249615 and EMD 219906 had no significant effect. These data suggest that EMD249615, EMD 219906, EMD273316 & EMD95833 can promote the recruitment of bone marrow osteoprogenitor cel...Continue Reading

References

Mar 1, 1995·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·A Scutt, P Bertram
Oct 23, 1997·Biochemical Pharmacology·K MiyamotoK Ohya
Mar 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·L FawcettS C Phillips
Nov 16, 2002·Prostaglandins & Other Lipid Mediators·Ikuo Morita
Aug 22, 2003·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Ken-ichi MiyamotoHideomi Yamagami

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Citations

Feb 27, 2010·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Christiane StollGundula Schulze-Tanzil
Apr 23, 2013·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Tanya ZappitelliJane E Aubin
Mar 24, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Shinsaku TogoStephen I Rennard

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Datasets Mentioned

BETA
EMD219906
EMD249615

Methods Mentioned

BETA
ELISA

Software Mentioned

Bioimage " Intelligent Quantifier
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