Characterization of zinc effect to inhibit osteoclast-like cell formation in mouse marrow culture: interaction with dexamethasone

Abstract

The inhibitory effect of zinc compounds on osteoclast-like cell formation in mouse marrow culture in vitro was characterized. The bone marrow cells were cultured for 7 days in alpha-minimal essential medium containing a well-known bone resorbing agent, 1,25-dihydroxyvitamin D3[1,25(OH)2D3] or prostaglandin E2 (PGE2). Osteoclast-like cell formation was estimated by staining for tartrate-resistant acid phosphatase (TRACP), a marker enzyme of osteoclasts. The presence of 1,25(OH)2D3 (10(-8) M) or PGE2 (10(-6) M) induced a remarkable increase in osteoclast-like multinucleated cells. These increases were enhanced by the presence of dexamethasone (10(-9) to 10(-6) M). The dexamethasone (10(-7) M)-enhanced osteoclast-like cell formation was not inhibited by the presence of zinc sulfate (10(-6) M) or zinc-chelating dipeptide (beta-alanyl-L-histidinato zinc; 10(-6) M), although the zinc compounds had an inhibitory effect on osteoclastic formation in the absence of the steroid. The effect of dexamethasone was not seen, when the steroid was added at the later stage of culture with bone-resorbing agents. In this case, the inhibitory effect of zinc compounds was clearly revealed. This effect of zinc compounds disappeared in the presence of Ca2+-chelating agent (0.5 mM EGTA). The present study suggests that zinc compounds have an inhibitory effect at the stage of differentiation of preosteoclastic cells in bone marrow cell culture system.