title: Genetic approaches to determine the role of glucocorticoid signaling in osteoblasts.
abstract: A variety of in vivo and in vitro experimental models have been used to explore the effects of glucococorticoids in bone. Chronically high levels of glucocorticoids typically decrease bone mass in humans and animals and inhibit markers of bone formation in organ and cell cultures. However, under certain experimental conditions, glucocorticoids can stimulate osteoblast differentiation and bone formation in vitro. The relevance of these effects seen in culture models to the role of endogenous glucocorticoids in bone remains unclear. In this article, we briefly review possible pathways for the opposing effects of glucocorticoids on bone formation and propose several genetic loss-of-function mouse models in which disruption of glucocorticoid signaling in cells of the osteoblast lineage would provide a means to determine the role of endogenous glucocorticoids in bone.
authors.affiliation: Department of Orthodontics, School of Dental Medicine, University of Connecticut Health Center, Farmington, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Harrison
authors.forename: Henning W
authors.initials: HW
authors.lastname: Woitge
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Kream
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000818:Animals; D001846:Bone Development; D015870:Gene Expression; D005938:Glucocorticoids / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D014162:Transfection
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D006913:Hydroxysteroid Dehydrogenases; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human