| Research Abstract |
Osteoclastic bone resorption is associated with both the removal of bone mineral and the degradation of bone organic matrix through hydrolytic enzymes secreted by the cells. The present study was designed to investigate the role of lysosomal membrane proteins in the formation of acidic conditions of the bone resorption lacuna and the functional importance of lysosomal proteinases in the bone resorbing process. For this purpose, the levels and localizations of a major 107 kDa lysosomal membrane glycoprotein (designated as LGP107) and lysosomal proteinases (cathepsins B,L and D) in rat osteoclasts were determined by immunocytochemical techniques using antibodies specific for each enzyme. LGP107 was exclusively confined to the apical plasma membrane at the ruffled border of active osteoclasts, where the cells were contact with the bone surface. The ruffled border membrane detached from the bone surface showed a marked decrease in the extent of the immunolabeling. Since LGP107 is highly sialylated and has the very low pI, the protein is likely to contribute to the formation and maintenance of the bone resorption lacuna. Extracellular localization of cathepsins B and L, lysosomal cysteine proteinases, was clearly shown along the bone resorption lacuna and the intracellular immunoreactivity of both cathepsins was weak compared with that of cathepsin D,a lysosomal aspartic proteinase. Cathepsin D was intensely observed in the granules and vacuoles of the osteoclasts, but its extracellular localization was either negligible or not detected along the bone resorption lacuna. These results suggest that these proteinases have their shares of the degradation of the bone matrix.
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