Bone resorbing osteoclasts reveal two basal plasma membrane domains and transcytosis of degraded matrix material

Abstract

<div lang="en" class="abs"><p class="abs_header">Abstract</p><p>Changes of cellular polarity in osteoclasts during resorption cycle was studied. Targeting of vesicular stomatitis virus (VSV) G-protein has earlier been studied in epithelial cells and in neurons, in which it serves as a basolateral or dendritic marker protein, respectively. In osteoclasts it occupied only the peripheral parts of the circulation facing basal membrane, but not ruffled border membrane or sealing zone area. Apical or axonal markers including Influenza A haemagglutinin were neither targeted to ruffled border area. Instead, they were transported to a limited area in the middle of the osteoclast basal surface. This membrane domain also showed staining for organic bone matrix components. Further works were done to find out the route of degraded bone matrix components to this membrane domain. It is shown in the confocal laser scanning and transmission electron microscopic level that osteoclasts take both organic and inorganic bone matrix dissolution products into intracellular vesicles which then are transcytosed to basal surface and finally exocytosed. One biological function to the new membrane domain seems to be to serve as an endpoint for intracellular handling of degraded bone matrix components, and as a final secretion point to release these components to circulation. This specialized membrane area is named as functional secretory domain (FSD) in this study. Membrane associated fine structures on the FSD area showed some novel membrane associsted structures. Their appearance and amount correlated to the resorption activity of osteoclasts suggesting that these new structures, termed clastosomes and debris, could be directly involved in the handling of bone degradation products during resorption. It is also shown that the bone matrix itself has effect on the resorption activity of cultured osteoclasts.</p></div>