Cathepsin B Inhibitor CA-074 Me Inhibits Osteoclastogenesis In Vivo and Promotes Calcineurin Cleavage in Murine Bone Marrow-der

INTRODUCTION: Osteoclasts are multinucleated, specialized cells responsible for bone resorption and play important roles in the maintenance of normal bone structure and function. At least dozens of genes have been shown to positively and negatively regulate osteoclastogenesis and osteoclast activation.TRAP and cathepsin K are the two mail enzymes responsible for the degradation of bone mineral and collagen matrices, and cathepsin K knockout mice were shown to develop osteopetrosis due to a deficit in matrix degradation. It is demonstrated that cathepsin K is the predominant cysteine protease expressed in human osteoclast, however, cathepsins B, D and L are also detected in the rat osteoclasts. Cathepsin B is implicated a number of inflammatory diseases and pathological conditions, such as bronchitis, rheumatoid arthritis, acute pancreatisis and cancer progression. To elucidate its role in the bone, in the present study, we examined the role of cathepsin B in the regulation of RANKL-supported osteoclastogenesis.