Department of Cell Biology, University Medical Center, Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Traffic. 2011 Jul;12(7):912-24. doi: 10.1111/j.1600-0854.2011.01203.x. Epub 2011 May 5.
Osteoclasts are specialized cells that secrete lysosomal acid hydrolases at the site of bone resorption, a process critical for skeletal formation and remodeling. However, the cellular mechanism underlying this secretion and the organization of the endo-lysosomal system of osteoclasts have remained unclear. We report that osteoclasts differentiated in vitro from murine bone marrow macrophages contain two types of lysosomes. The major species is a secretory lysosome containing cathepsin K and tartrate-resistant acid phosphatase (TRAP), two hydrolases critical for bone resorption. These secretory lysosomes are shown to fuse with the plasma membrane, allowing the regulated release of acid hydrolases at the site of bone resorption. The other type of lysosome contains cathepsin D, but little cathepsin K or TRAP. Osteoclasts from Gnptab(-/-) (gene encoding GlcNAc-1-phosphotransferase α, β-subunits) mice, which lack a functional mannose 6-phosphate (Man-6-P) targeting pathway, show increased secretion of cathepsin K and TRAP and impaired secretory lysosome formation. However, cathepsin D targeting was intact, showing that osteoclasts have a Man-6-P-independent pathway for selected acid hydrolases.
破骨细胞是一种专门的细胞，能够在骨吸收部位分泌溶酶体酸性水解酶，这一过程对骨骼的形成和重塑至关重要。然而，这种分泌的细胞机制和破骨细胞内溶酶体系统的组织仍然不清楚。我们报告称，体外从鼠骨髓巨噬细胞分化而来的破骨细胞含有两种类型的溶酶体。主要的溶酶体是一种分泌性溶酶体，含有组织蛋白酶 K 和抗酒石酸酸性磷酸酶（TRAP），这两种水解酶对骨吸收至关重要。这些分泌性溶酶体被证明可以与质膜融合，允许在骨吸收部位有调节地释放酸性水解酶。另一种类型的溶酶体含有组织蛋白酶 D，但几乎没有组织蛋白酶 K 或 TRAP。缺乏功能性甘露糖 6-磷酸（Man-6-P）靶向途径的 Gnptab(-/-)（编码 GlcNAc-1-磷酸转移酶 α、β 亚基的基因）小鼠的破骨细胞显示出组织蛋白酶 K 和 TRAP 的分泌增加以及分泌性溶酶体形成受损。然而，组织蛋白酶 D 的靶向是完整的，表明破骨细胞有一个 Man-6-P 非依赖性途径用于特定的酸性水解酶。
