title: Dexamethasone stimulates osteoclast-like cell formation by directly acting on hemopoietic blast cells and enhances osteoclast-like cell formation stimulated by parathyroid hormone and prostaglandin E2.
abstract: Although an excess of glucocorticoid induces secondary osteoporosis, the mechanism still remains unclear, particularly in regard to glucocorticoid-stimulated bone resorption. We examined the effects of dexamethasone (Dex) on osteoclast-like cell formation and bone-resorbing activity by employing mouse bone and spleen cell cultures and further investigated whether Dex would modulate osteoclast-like cell formation stimulated by several bone-resorbing factors. Dex stimulated osteoclast-like cell formation in stromal cell-containing mouse bone cell cultures in a concentration-dependent manner. Also, Dex significantly stimulated osteoclast-like cell formation from hemopoietic blast cells in spleen cell cultures derived from 5-fluorouracil-pretreated mice. In contrast, Dex (10(-8) M) did not affect the bone-resorbing activity of mature osteoclasts. Pretreatment with 10(-8) M Dex significantly enhanced osteoclast-like cell formation in unfractionated mouse bone cell cultures stimulated by 10(-8) M human (h) parathyroid hormone (PTH) (1-34), 10(-8) M hPTH-related protein (1-34) and 10(-6) M prostaglandin E2, but not by 10(-8) M 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Moreover, pretreatment with 10(-8) M Dex significantly enhanced osteoclast-like cell formation stimulated by both forskolin and dbcAMP. In contrast, pretreatment with 10(-8) M Dex significantly inhibited osteoclast-like cell formation in mouse spleen cell cultures stimulated by both 10(-8) M hPTH(1-34) and 10(-8) M 1,25(OH)2D3. These findings suggest that Dex stimulates osteoclast-like cell formation, at least in part by directly acting on hemopoietic blast cells. They further suggest that Dex enhances osteoclast-like cell formation stimulated by PTH and prostaglandin E2 through an indirect pathway via cells other than hemopoietic blast cells.
authors.affiliation: Department of Medicine, Kobe University School of Medicine, Chuo-ku, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kaji
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
authors.forename: M
authors.initials: M
authors.lastname: Kanatani
authors.forename: K
authors.initials: K
authors.lastname: Nishiyama
authors.forename: K
authors.initials: K
authors.lastname: Chihara
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced; D002117:Calcitriol / Q000494:pharmacology; D002458:Cell Fractionation; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013268:Stimulation, Chemical
chemical_list: D005938:Glucocorticoids; D010281:Parathyroid Hormone; D003907:Dexamethasone; D002117:Calcitriol; D015232:Dinoprostone