title: Mechanical loading down-regulates peroxisome proliferator-activated receptor gamma in bone marrow stromal cells and favors osteoblastogenesis at the expense of adipogenesis.
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 gamma (PPARgamma)-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 PPARgamma2 protein levels. Given the proadipocytic and antiosteoblastic activities of PPARgamma, we studied the effects of cyclic stretching in C3H10T1/2 cells, treated either with the PPARgamma activator, Rosiglitazone, or with GW9662, a potent antagonist of PPARgamma. 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 PPARgamma modulators counteracting adipocyte differentiation and inhibition of osteoblastogenesis.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 890, Université Jean Monnet, F-42023 Saint-Etienne Cedex 2, France.
authors.forename: Valentin
authors.initials: V
authors.lastname: David
authors.forename: Aline
authors.initials: A
authors.lastname: Martin
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Lafage-Proust
authors.forename: Luc
authors.initials: L
authors.lastname: Malaval
authors.forename: Sylvie
authors.initials: S
authors.lastname: Peyroche
authors.forename: David B
authors.initials: DB
authors.lastname: Jones
authors.forename: Laurence
authors.initials: L
authors.lastname: Vico
authors.forename: Alain
authors.initials: A
authors.lastname: Guignandon
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000502:physiology; D050156:Adipogenesis / Q000502:physiology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology*; D002417:Cattle; D002454:Cell Differentiation / Q000502:physiology; D002461:Cell Line, Transformed; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology* / Q000502:physiology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D013977:Tibia / Q000166:cytology / Q000502:physiology
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D047495:PPAR gamma