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.