title: Prostaglandin E2 impairs osteogenic and facilitates adipogenic differentiation of human bone marrow stromal cells.
abstract: The synthetic glucocorticoid dexamethasone (dex) is a mandatory additive to induce osteogenic differentiation of bone marrow stromal cell (BMSC) in vitro; however it is also known to promote the pathogenesis of osteoporotic bone disease in vivo. In this study human (h)BMSC were cultured in osteogenic medium containing β-glycerophosphate and ascorbate (OM) and in OM containing dex (OM/D). It was seen that dex induced in human (h)BMSC both, osteogenic and adipogenic differentiation markers. Dex reveals its anti-inflammatory effect by reducing endogenous prostaglandin E2 (PGE2) formation and by suppressing the inducible enzymes cyclooxygenase 2 and microsomal PGE2 synthase 1. It was further seen that dex enhanced the expression of prostaglandin receptors, mainly EP2 and EP4 receptor subtypes. We thus hypothesized that dex enforces the susceptibility of hBMSC to respond to exogenous PGE2. Permanent exposure of hBMSC which were cultured in OM/D to PGE2, decreased osteogenic and increased adipogenic differentiation markers. The effects of PGE2 were preferentially mediated by receptor subtypes EP2 and EP4; EP1 was partially involved in pro-adipogenic effects, and EP3 was partially involved in anti-osteogenic effects. These results suggest that dex suppresses the formation of endogenous PGE2 but also enables hBMSC to respond to PGE2 due to the induction of PGE2 receptors EP2 and EP4. PGE2 then shifts in hBMSC the balance from osteogenic to adipogenic differentiation.
authors.affiliation: Institute of Physiological Chemistry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Fiedlerstrasse 42, D-01307 Dresden, Germany. Electronic address: Carolin.Noack@crt-dresden.de.
authors.forename: Carolin
authors.initials: C
authors.lastname: Noack
authors.affiliation: Institute of Physiological Chemistry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Fiedlerstrasse 42, D-01307 Dresden, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Hempel
authors.affiliation: Institute of Physiological Chemistry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Fiedlerstrasse 42, D-01307 Dresden, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Preissler
authors.affiliation: Institute of Physiological Chemistry, Carl Gustav Carus Faculty of Medicine, Technische Universität Dresden, Fiedlerstrasse 42, D-01307 Dresden, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Dieter
mesh_terms: D050156:Adipogenesis / Q000187:drug effects*; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism
chemical_list: D003470:Culture Media; C545644:PTGER2 protein, human; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D003907:Dexamethasone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone
keywords: Adipogenic differentiation; Dexamethasone; Human bone marrow stromal cells; Inflammation; Osteogenic differentiation; Prostaglandin E(2)