SECRETION AND PROCESSING MECHANISMS OF PROCATHEPSIN-L IN BONE-RESORPTION

Secretion of procathepsin L into the culture medium from a bone cell m ixture was markedly enhanced by addition of parathyroid hormone (PTH), 1 alpha,25-(OH)(2)D-3 or tumor necrosis factor alpha (TNF alpha), The se stimulators of secretion of procathepsin L enhanced bone pit format ion, which was inhibited by E-64, but not by CA-074, a specific inhibi tor of cathepsin B. Procathepsin L may thus participate in the process of bone collagenolysis during bone resorption, Procathepsin L partial ly purified from rat long bones under cold conditions was rapidly conv erted to the mature form under acidic conditions at room temperature, This conversion was inhibited by E-64, suggesting that the procathepsi n L secreted into lacunae is catalytically converted to the mature enz yme by cysteine proteinase(s).