Concanamycin B, a Vacuolar H⁺-ATPase Specific Inhibitor Suppresses Bone Resorption in Vitro

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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 found to inhibit PTH-stimulated osteoclastic pit formation and to suppress the acidification of vacuolar organelles by V-ATPase in the osteoclasts. PTH-stimulated ⁴⁵Ca release from prelabelled chick embryonic calvariae was also inhibited by concanamycin B in a dose-dependent manner. These results suggest that osteoclastic acidification of lacunae by V-ATPase plays an essential role in mineral dissolution and degradation of the organic matrix during bone resorption.