Glucocorticoid receptor signaling in bone cells

Glucocorticoids are used for treating a wide range of diseases including inflammation and autoimmune disorders. However, there are drawbacks, primarily due to adverse effects on bone cells resulting in osteoporosis. Evidence indicates that the ratio of benefits to adverse effects depends greatly on glucocorticoid receptor (GR)-mediated mechanisms. Delineating GR-mediated signaling in bone cells will allow development of selective GR ligands/agonists (SEGRAs), which would dissociate the positive therapeutic (anti-inflammatory) effects from the negative effects on the skeleton. The present review provides an in-depth account of the current knowledge of GR-mediated transcriptional regulation of specific genes and proteins engaged in the proliferation, differentiation, and apoptosis of bone cells (osteoblasts, osteocytes, osteoclasts). We hope this knowledge will advance research in the development of SEGRAs with improved benefit/risk ratios.