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Submitted on December 18, 2006
Accepted on February 9, 2007
in bone marrow stromal cells and favours osteoblastogenesis at the expense of adipogenesis
INSERM U890, St-Etienne, F-42023 France; Université Jean Monnet, St Etienne, F-42023 France.; Experimental Orthopaedics and Biomechanics, Philipps University, Baldingerst, D-35033 Marburg, Germany
* To whom correspondence should be addressed. E-mail: Alain.Guignandon{at}univ-st-etienne.fr.
Because a lack of mechanical information favors the development of adipocytes at the expense of osteoblasts, we hypothesized that the PPAR
-dependent balance between osteoblasts and adipocytes is affected by mechanical stimuli. We tested the robustness of this hypothesis in in vivo rodent osteogenic exercise, in vitro cyclic loading of cancellous haversian bone samples and cyclic stretching of primary stromal and C3H10T1/2 cells. We found that running rats exhibit a decreased marrow fat volume associated with an increased bone formation, presumably through recruitment of osteoprogenitors. In the tissue culture model and primary stromal cells cyclic loading induced higher Runx2 and lower PPAR2 protein levels. Given the pro-adipocytic and anti-osteoblastic activities of PPAR, we studied the effects of cyclic stretching in C3H10T1/2 cells, treated either with the PPAR activator, Rosiglitazone, or with GW9662, a potent antagonist of PPAR. We found, through both cytochemistry and analysis of lineage marker expression, that under Roziglitazone cyclic stretch partially overcomes the induction of adipogenesis and is still able to favor osteoblast differentiation. Conversely, cyclic stretch has additive effects with GW9662 in inducing osteoblastogenesis. In conclusion, we provide evidence that mechanical stimuli are potential PPAR modulators counteracting adipocyte differentiation and inhibition of osteoblastogenesis.
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Runx2 •
bioreactor •
FlexerCell •
running rats •
C3H10T1/2
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