CONCANAMYCIN-B, A VACUOLAR H-ATPASE SPECIFIC INHIBITOR SUPPRESSES BONE-RESORPTION IN-VITRO()

Effects of concanamycin B, a specific inhibitor of the vacuolar type H +-ATPase (V-ATPase), on the stimulation of bone resorption induced by parathyroid hormone (PTH) were examined in vitro. Concanamycin B was f ound to inhibit PTH-stimulated osteoclastic pit formation and to suppr ess the acidification of vacuolar organelles by V-ATPase in the osteoc lasts. PTH-stimulated Ca-45 release from prelabelled chick embryonic c alvariae was also inhibited by concanamycin B in a dose-dependent mann er, These results suggest that osteoclastic acidification of lacunae b y V-ATPase plays an essential role in mineral dissolution and degradat ion of the organic matrix during bone resorption.