Event:

Glucocorticoids have profound effects on the immune system and on bone leading to immune suppression and glucocorticoid-induced osteoporosis, respectively. The glucocorticoid receptor (GR) is a hormone-induced transcription factor controlling gene expression as a monomer or dimeric molecule. We demonstrated- in contrast to the prevailing view - that the induction of genes by dimeric GR molecules suppresses inflammation in disease models. This function of the GR is required to induce inflammation resolving macrophages by either cell-autonomous or cell-non-autonomous effects. In contrast the monomer GR mediates inhibition of bone formation and bone loss. Using high content screen analysis, we identified novel modulators that abrogate the deleterious effects of glucocorticoids on bone. Our mechanistic studies provide new drug targets and rationales for improved steroid therapy with lesser side effects.