Mechanical loading down-regulates peroxisome proliferator-activated receptor γ in bone marrow stromal cells and favors osteoblastogenesis at the expense of adipogenesis

Valentin David, Aline Martin, Marie Hélène Lafage-Proust, Luc Malaval, Sylvie Peyroche, David B. Jones, Laurence Vico, Alain Guignandon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

232 Scopus citations

Abstract

Because a lack of mechanical information favors the development of adipocytes at the expense of osteoblasts, we hypothesized that the peroxisome proliferator-activated receptor γ (PPARγ)-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 PPARγ2 protein levels. Given the proadipocytic and antiosteoblastic activities of PPARγ, we studied the effects of cyclic stretching in C3H10T1/2 cells, treated either with the PPARγ activator, Rosiglitazone, or with GW9662, a potent antagonist of PPARγ. 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 PPARγ modulators counteracting adipocyte differentiation and inhibition of osteoblastogenesis.

Original languageEnglish (US)
Pages (from-to)2553-2562
Number of pages10
JournalEndocrinology
Volume148
Issue number5
DOIs
StatePublished - May 2007

ASJC Scopus subject areas

  • Endocrinology

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