Dexamethasone stimulates osteoclast-like cell formation by inhibiting granulocyte-macrophage colony-stimulating factor production in mouse bone marrow cultures.
We investigated the effect of glucocorticoid on the generation of osteoclasts. In mouse bone marrow culture systems, dexamethasone, a synthetic glucocorticoid analog, enhanced osteoclast-like cell formation induced by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in a dose-dependent manner. Conversely, dexamethasone inhibited the endogenous production of granulocyte-macrophage colony-stimulating factor (GM-CSF) in bone marrow cultures. GM-CSF, when added exogenously, suppressed not only the osteoclast-like cell formation induced by 1,25-(OH)2D3, but also the stimulatory effect of dexamethasone, and addition of anti-GM-CSF neutralizing antibody to the cultures significantly increased the osteoclast-like cell formation induced by 1,25-(OH)2D3. These observations suggest that dexamethasone directly affects bone marrow cells and enhances osteoclast generation by inhibiting the endogenous production of GM-CSF, which may function as a negative regulator of osteoclast formation.
Shuto
T
T
Department of Biochemistry, Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
Kukita
T
T
Hirata
M
M
Jimi
E
E
Koga
T
T
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology; D046508:Culture Techniques; D003907:Dexamethasone / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism
D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase; D002117:Calcitriol