Distinct roles of cathepsin K and cathepsin L in osteoclastic bone resorption.
The role of cathepsin K (CAK), cloned as a novel collagenolytic cysteine protease (CCP), cathepsin L (CAL) and cathepsin B (CAB) in bone resorption was investigated. In mouse calvarial organ culture medium, CAL, detected in trace amounts in control conditions, and CCP activity were increased by stimulants of bone resorption: 1alpha,25-(OH)2D3 parathyroid hormone (PTH), IL-1alpha, IL-6 or TNF-alpha. CAK was the most abundantly detected CCP and was not increased by these stimulants. In the absence of the stimulants, only antisense oligodeoxynucleotide (AS-ODN) for CAK suppressed collagenolysis 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, and these activities were additive. AS-ODN for CAB did not suppress collagenolysis. These results suggested CAK was constitutively synthesized as the main CCP, and CAL was synthesized as an inducible CCP in osteoclasts to degrade type-I collagen in combination with CAK.
Discovery Research Laboratory, Takeda Chemical Industries, Ltd., Osaka, Japan.
N
N
Furuyama
Y
Y
Fujisawa
D000818:Animals; D001862:Bone Resorption; D001842:Bone and Bones / Q000196:embryology / Q000502:physiology; D002117:Calcitriol / Q000494:pharmacology; D056657:Cathepsin K; D056668:Cathepsin L; D002403:Cathepsins / Q000502:physiology*; D002454:Cell Differentiation; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009924:Organ Culture Techniques; D010010:Osteoclasts / Q000502:physiology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D016376:Oligonucleotides, Antisense; D010281:Parathyroid Hormone; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L; C534278:Ctsl protein, mouse; D056657:Cathepsin K; C534132:Ctsk protein, mouse; D002117:Calcitriol