There is increasing evidence that
calpain contributes to the reorganization of the cytoskeleton in the
integrin-mediated signaling pathway. Osteoclastic
bone resorption requires cell-matrix contact, an event mediated by
integrin alphavbeta3, and subsequent cytoskeletal reorganization to form characteristic membrane domains such as the sealing zone and ruffled border. In this study, therefore, we investigated whether
calpain is involved in osteoclastic
bone resorption. Membrane-permeable
calpain inhibitors suppress the resorption activity of human osteoclasts, but an impermeable inhibitor does not. Upon the attachment of osteoclasts to bone, micro-
calpain is translocated from the cytosolic to the cytoskeletal fraction and is autolytically activated. Both the activation of micro-
calpain and the formation of actin-rings, the cytoskeletal structures essential for
bone resorption, are inhibited by membrane-permeable
calpain inhibitors. The activated micro-
calpain in osteoclasts selectively cleaves
talin, which links the matrix-recognizing
integrin to the actin cytoskeleton. These findings suggest that
calpain is a regulator of the
bone resorption activity of osteoclasts through reorganization of the cytoskeleton related to actin-ring formation.