The role of pp60c-src activity in the synthesis and secretion of the collag
enolytic cysteine proteases (CCPs), cathepsin K (CAK), cathepsin L (CAL), a
nd cathepsin B (CAB), by osteoclasts was investigated. Synthesis and secret
ion of CAL were up-regulated by 1 alpha,25-(OH)(2)D-3, but neither those of
CAK dominant relative to GAL, nor CAB, barely detectable, levels changed i
n the experiments. Though PP1, a pp60(c-sre) inhibitor, had no effect on CC
Ps synthesis, suppressed the CAK and CAL secretion. Wortmannin, a phosphati
dylinositol 3-kinase (PI3-kinase) inhibitor that works as a second messenge
r for pp60(c-src), and cytochalasin B, an inhibitor of actin polymerization
, suppressed the secretion of both CAK and CAL without suppressing synthesi
s. Hydroxyproline release, an indicator of degradation of type-I collagen,
and F-actin ring formation, a structure linked to osteoclastic bone resorpt
ion, were suppressed by PP1, cytochalasin B or wortmannin. These results su
ggested inhibition of pp60(c-src) activity affected the osteoclastic cytosk
eleton, which in turn reflected the suppression of bone resorption. (C) 200
0 Academic Press.