Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor

Official URL:https://doi.org/10.1016/j.cmet.2010.05.005
PubMed:View item in PubMed
Creators Name:Rauch, A. and Seitz, S. and Baschant, U. and Schilling, A.F. and Illing, A. and Stride, B. and Kirilov, M. and Mandic, V. and Takacz, A. and Schmidt-Ullrich, R. and Ostermay, S. and Schinke, T. and Spanbroek, R. and Zaiss, M.M. and Angel, P.E. and Lerner, U.H. and David, J.P. and Reichardt, H.M. and Amling, M. and Schuetz, G. and Tuckermann, J.P.
Journal Title:Cell Metabolism
Journal Abbreviation:Cell Metab
Volume:11
Number:6
Page Range:517-531
Date:9 June 2010
Keywords:Apoptosis, Cell Differentiation, Dimerization, Glucocorticoids, Interleukin-11, Osteoblasts, Osteogenesis, Glucocorticoid Receptors, Transcription Factor AP-1, Animals, Mice
Abstract:Development of osteoporosis severely complicates long-term glucocorticoid (GC) therapy. Using a Cre-transgenic mouse line, we now demonstrate that GCs are unable to repress bone formation in the absence of glucocorticoid receptor (GR) expression in osteoblasts as they become refractory to hormone-induced apoptosis, inhibition of proliferation, and differentiation. In contrast, GC treatment still reduces bone formation in mice carrying a mutation that only disrupts GR dimerization, resulting in bone loss in vivo, enhanced apoptosis, and suppressed differentiation in vitro. The inhibitory GC effects on osteoblasts can be explained by a mechanism involving suppression of cytokines, such as interleukin 11, via interaction of the monomeric GR with AP-1, but not NF-kappaB. Thus, GCs inhibit cytokines independent of GR dimerization and thereby attenuate osteoblast differentiation, which accounts, in part, for bone loss during GC therapy.
ISSN:1550-4131
Publisher:Cell Press (U.S.A.)
Item Type:Article

Repository Staff Only: item control page

Open Access
MDC Library