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Glucocorticoids sup...
Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor.
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Rauch, Alexander (author)
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Seitz, Sebastian (author)
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Baschant, Ulrike (author)
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Schilling, Arndt F (author)
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Illing, Anett (author)
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Stride, Brenda (author)
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Kirilov, Milen (author)
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Mandic, Vice (author)
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Takacz, Andrea (author)
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Schmidt-Ullrich, Ruth (author)
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Ostermay, Susanne (author)
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Schinke, Thorsten (author)
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Spanbroek, Rainer (author)
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Zaiss, Mario M (author)
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Angel, Peter E (author)
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- Lerner, Ulf H (author)
- Umeå universitet,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine,Oral cellbiologi
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David, Jean-Pierre (author)
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Reichardt, Holger M (author)
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Amling, Michael (author)
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Schütz, Günther (author)
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Tuckermann, Jan P (author)
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(creator_code:org_t)
- Elsevier BV, 2010
- 2010
- English.
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In: Cell metabolism. - : Elsevier BV. - 1932-7420 .- 1550-4131. ; 11:6, s. 517-31
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Animals
- Apoptosis
- Cell Differentiation
- Dimerization
- Glucocorticoids
- toxicity
- Interleukin-11
- metabolism
- Mice
- Mice
- Knockout
- Osteoblasts
- cytology
- drug effects
- Osteogenesis
- drug effects
- Receptors
- Glucocorticoid
- genetics
- metabolism
- Transcription Factor AP-1
- metabolism
- induced osteoporosis; gene-expression; dna-binding; cell-cycle; mice; inhibition; interleukin-11; osteoclast; mechanisms; phenotype
- Cell biology
- odontologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Rauch, Alexander
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Seitz, Sebastian
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Baschant, Ulrike
-
Schilling, Arndt ...
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Illing, Anett
-
Stride, Brenda
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show more...
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Kirilov, Milen
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Mandic, Vice
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Takacz, Andrea
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Schmidt-Ullrich, ...
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Ostermay, Susann ...
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Schinke, Thorste ...
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Spanbroek, Raine ...
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Zaiss, Mario M
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Angel, Peter E
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Lerner, Ulf H
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David, Jean-Pier ...
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Reichardt, Holge ...
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Amling, Michael
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Schütz, Günther
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Tuckermann, Jan ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Cell metabolism
- By the university
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University of Gothenburg
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Umeå University