Secretion and processing mechanisms of procathepsin L in bone resorption

Secretion of procathepsin L into the culture medium from a bone cell mixture was markedly enhanced by addition parathyroid hormone (PTH), 1α,25-(OH) 2D 3 or tumor necrosis factor α (TNF α). These stimulators of secretion of procathepsin L enhanced bone pit formation, which was inhibited by E-64, but not by CA-074, a specific inhibitor of cathepsin B. Procathepsin L may thus participate in the process of bone collagenolysis during bone resorption. Procathepsin L partially purified from rat long bones under cold conditions was rapidly converted to the mature form under acidic conditions at room temperature. This conversion was inhibited by E-64, suggesting that the procathepsin L secreted into lacunae is catalytically converted to the mature enzyme by cysteine proteinase(s).