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Forskolin enhances in vivo bone formation by human mesenchymal stromal cells.
MedLine Citation:
PMID:  21942968     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Activation of the protein kinase A (PKA) pathway with dibutyryl-cAMP (db-cAMP) was recently shown to enhance osteogenic differentiation of human mesenchymal stromal cells (hMSCs) in vitro as well as bone formation in vivo. The major drawback of this compound is its inhibitory effect on proliferation of hMSCs. Therefore, we investigated if fine-tuning of the dose and timing of PKA activation could potentially enhance bone formation even further, with minimum effects on proliferation. To test this, we selected two different PKA activators, 8-bromo-cAMP and forskolin, and tested their effects on proliferation and osteogenic differentiation, in comparison with db-cAMP. We found that indeed ALP levels, bone specific target genes and secretion of insulin-like growth factor-1 were induced by all three compounds, although 8-br-cAMP induced adipogenic differentiation in long term cultures and was thus considered unsuitable for further in vivo testing. All three compounds inhibited proliferation of hMSCs in a dose-dependent manner, with forskolin inhibiting proliferation most. The effect of forskolin on in vivo bone formation was tested by pre-treating hMSCs prior to implantations and we observed increased amounts of bone using forskolin compared to db-cAMP. Our data shows forskolin as a novel agent that can be used to increase bone formation and also suggests a role for PKA in the delicate balance between adipogenic and osteogenic differentiation.
Authors:
Joyce Doorn; Ramakrishnaiah Siddappa; Clemens van Blitterswijk; Jan De Boer
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-26
Journal Detail:
Title:  Tissue engineering. Part A     Volume:  -     ISSN:  1937-335X     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101466659     Medline TA:  Tissue Eng Part A     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
University of Twente, MIRA Institute for Biomedical Technology and Technical Medicine, Dept. of Tissue Regeneration, Enschede, Netherlands; joycedoorn1@gmail.com.
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