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


  • A. Rauch
  • S. Seitz
  • U. Baschant
  • A.F. Schilling
  • A. Illing
  • B. Stride
  • M. Kirilov
  • V. Mandic
  • A. Takacz
  • R. Schmidt-Ullrich
  • S. Ostermay
  • T. Schinke
  • R. Spanbroek
  • M.M. Zaiss
  • P.E. Angel
  • U.H. Lerner
  • J.P. David
  • H.M. Reichardt
  • M. Amling
  • G. Schuetz
  • J.P. Tuckermann


  • Cell Metabolism


  • Cell Metab 11 (6): 517-531


  • 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.