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| Item Type: | Article |
|---|---|
| Title: | Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor |
| Creators Name: | Rauch, A., Seitz, S., Baschant, U., Schilling, A.F., Illing, A., Stride, B., Kirilov, M., Mandic, V., Takacz, A., Schmidt-Ullrich, R., Ostermay, S., Schinke, T., Spanbroek, R., Zaiss, M.M., Angel, P.E., Lerner, U.H., David, J.P., Reichardt, H.M., Amling, M., Schuetz, G. and Tuckermann, J.P. |
| 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. |
| Keywords: | Apoptosis, Cell Differentiation, Dimerization, Glucocorticoids, Interleukin-11, Osteoblasts, Osteogenesis, Glucocorticoid Receptors, Transcription Factor AP-1, Animals, Mice |
| Source: | Cell Metabolism |
| ISSN: | 1550-4131 |
| Publisher: | Cell Press |
| Volume: | 11 |
| Number: | 6 |
| Page Range: | 517-531 |
| Date: | 9 June 2010 |
| Official Publication: | https://doi.org/10.1016/j.cmet.2010.05.005 |
| PubMed: | View item in PubMed |
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