title: Glucocorticoid regulation of osteoclast differentiation and expression of receptor activator of nuclear factor-kappaB (NF-kappaB) ligand, osteoprotegerin, and receptor activator of NF-kappaB in mouse calvarial bones.
abstract: In the present study, dexamethasone treatment of neonatal mouse calvarial bones increased mRNA expression of tartrate-resistant acid phosphatase, calcitonin receptor (CTR), cathepsin K, carbonic anhydrase II, osteoprotegerin (OPG), and receptor activator of nuclear factor-kappaB (RANK) as well as mRNA and protein expression of RANK ligand (RANKL). The increase in OPG mRNA noted with dexamethasone was in contrast to 1,25(OH)(2)-vitamin D3 (D3) treatment, which decreased OPG expression. Stimulation of (45)Ca release by dexamethasone and hydrocortisone in calvariae was blocked by OPG. Stimulation of RANKL, RANK, OPG, and CTR mRNA expression by dexamethasone in calvariae was blocked by the glucocorticoid receptor antagonist RU 38,486. Greater than additive potentiations of CTR mRNA and RANKL mRNA and protein were observed when D3 and dexamethasone were combined. Vitamin D receptor mRNA was increased by dexamethasone and D3, whereas glucocorticoid receptor (GR) mRNA was decreased by dexamethasone and unaffected by D3. No synergistic interaction between dexamethasone and D3 on either vitamin D receptor or GR mRNA expression was noted. The data demonstrate that dexamethasone-induced bone resorption in calvarial bones is associated with increased differentiation of osteoclasts and regulation of the RANKL-RANK-OPG system. The increase in OPG expression and the decrease of GR expression noted with dexamethasone offer an explanation for why bone breakdown in mouse calvariae treated with glucocorticoids is less than that caused by resorptive agents like D3. The synergistic stimulation of RANKL by dexamethasone and D3 offers an explanation of how glucocorticoids and D3 interact to potentiate bone resorption.
authors.affiliation: Department of Oral Cell Biology, Umeå University, Umeå SE-901 87, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Swanson
authors.forename: Mattias
authors.initials: M
authors.lastname: Lorentzon
authors.forename: H Herschel
authors.initials: HH
authors.lastname: Conaway
authors.forename: Ulf H
authors.initials: UH
authors.lastname: Lerner
mesh_terms: D000818:Animals; D001862:Bone Resorption; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology; D005938:Glucocorticoids / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology*; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D012886:Skull / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D005938:Glucocorticoids; D006023:Glycoproteins; D008024:Ligands; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D011965:Receptors, Glucocorticoid; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D015735:Mifepristone; D003907:Dexamethasone