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  • 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.
    Author: Kaji H, Sugimoto T, Kanatani M, Nishiyama K, Chihara K.
    Journal: J Bone Miner Res; 1997 May; 12(5):734-41. PubMed ID: 9144339.
    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.
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