Distinct roles of cathepsin K and cathepsin L in osteoclastic bone resorption

The role of cathepsin K (CAK), cloned as a novel collagenolytic cysteine pr otease (CCP), cathepsin L (CAL) and cathepsin B (CAB) in bone resorption wa s investigated. In mouse calvarial organ culture medium, GAL, detected in t race amounts in control conditions, and CCP activity were increased by stim ulants of bone resorption: 1 alpha,25-(0H)(2)D-3 parathyroid hormone (PTH), IL-1 alpha, IL-6 or TNF-alpha. CAK was the most abundantly detected CCP an d was not increased by these stimulants. In the absence of the stimulants, only antisense oligodeoxynucleotide (AS-ODN) for CAK suppressed collagenoly sis and CCP activity. On the other hand, in the presence of the stimulants, AS-ODN for both CAK and CAL suppressed collagenolysis and CCP activity, an d these activities were additive. AS-ODN for CAB did not suppress collageno lysis. These results suggested CAK was constitutively synthesized as the ma in CCP, and CAL was synthesized as an inducible CCP in osteoclasts to degra de type-I collagen in combination with CAK.