HIGH EXTRACELLULAR CALCIUM STIMULATES OSTEOCLAST-LIKE CELL-FORMATION AND BONE-RESORBING ACTIVITY IN THE PRESENCE OF OSTEOBLASTIC CELLS

The present study aas performed to examine the effect of the high conc entration of extracellular calcium ([Ca2+](e)) on osteoclast-like cell formation and bone-resorbing activity in the presence or absence of o steoblasts. High [Ca2+](e) (3 and 5 mM) significantly stimulated osteo clast-like cell formation in osteoblast-containing mouse bone cell cul tures, although high [Ca2+](e) did not affect the formation of osteocl ast-like cells from hemopoietic blast cells supported by granulocyte-m acrophage colony-stimulating factor in mouse spleen cell cultures. The osteoclast-like cells, newly formed by high [Ca2+](e) in the presence of osteoblasts, possessed the ability to form pits on the dentine sli ces, The conditioned medium from osteoblastic MC3T3-E1 cells treated w ith high [Ca2+](e) (5 mM) significantly increased the formation of ost eoclast-like cells from hemopoietic blast cells, compared with the con trol medium, Dantrolene, an inhibitor of calcium mobilization from the intracellular calcium pool, and indomethacin significantly blocked hi gh [Ca2+](e)-stimulated osteoclast-like cell formation in the presence of osteoblasts, although voltage-dependent calcium channel blockers a nd anti-insulin-like growth factor I antibody did not affect it. High [Ca2+](e), however, significantly stimulated the bone-resorbing activi ty of mature osteoclasts in osteoblast-containing mouse bone cell cult ures, although high [Ca2+](e) inhibited bone-resorbing activity in iso lated rabbit osteoclasts. An increase in the extracellular magnesium c oncentration (5 mM) affected neither osteoclast-like cell formation no r bone-resorbing activity. In conclusion, high [Ca2+](e) stimulated os teoclast-like cell formation and bone-resorbing activity of mature ost eoclasts, presumably via osteoblasts.