Participation of cathepsin L on bone resorption.
The proteinase responsible for bone collagen degradation in osteo-resorption was examined. The bone pit formation induced by parathyroid hormone (PTH) was markedly suppressed by leupeptin, E-64 and cystatin A, while no inhibition was observed by CA-074, a specific inhibitor of cathepsin B. Pig leucocyte cysteine proteinase inhibitor (PLCPI), a specific inhibitor of cathepsin L, and chymostatin, a selective inhibitor of cathepsin L, completely inhibited the pit formation. Cathepsin L activity in osteoclasts was much higher than the other cathepsin activities. Serum calcium in rats placed on a low calcium diet was decreased by treatment of E-64 or cystatin A, but not by CA-074. These findings suggest that cathepsin L is the main proteinase responsible for bone collagen degradation.
Kakegawa
H
H
Institute for Health Sciences, Tokushima Bunri University, Japan.
Nikawa
T
T
Tagami
K
K
Kamioka
H
H
Sumitani
K
K
Kawata
T
T
Drobnic-Kosorok
M
M
Lenarcic
B
B
Turk
V
V
Katunuma
N
N
D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption / Q000201:enzymology / Q000503:physiopathology*; D002118:Calcium / Q000097:blood; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D010450:Endopeptidases; D008297:Male; D010010:Osteoclasts / Q000187:drug effects / Q000201:enzymology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013379:Substrate Specificity
D015853:Cysteine Proteinase Inhibitors; D010281:Parathyroid Hormone; D011480:Protease Inhibitors; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; D056668:Cathepsin L; C534280:Ctsl protein, rat; D002118:Calcium