The proteinase responsible for bone collagen degradation in osteo-reso
rption was examined. The bone pit formation induced by parathyroid hor
mone (PTH) was markedly suppressed by leupeptin, E-64 and cystatin A,
while no inhibition was observed by CA-074, a specific inhibitor of ca
thepsin B. Pig leucocyte cysteine proteinase inhibitor (PLCPI), a spec
ific inhibitor of cathepsin L, and chymostatin, a selective inhibitor
of cathepsin L, completely inhibited the pit formation. Cathepsin L ac
tivity in osteoclasts was much higher than the other cathepsin activit
ies. 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 c
ollagen degradation.