Zhao H, Laitala-Leinonen T, Parikka V, Väänänen H K
Department of Anatomy, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland.
J Biol Chem. 2001 Oct 19;276(42):39295-302. doi: 10.1074/jbc.M010999200. Epub 2001 Aug 20.
During skeletal growth and remodeling the mineralized bone matrix is resorbed by osteoclasts through the constant secretion of protons and proteases to the bone surface. This relies on the formation of specialized plasma membrane domains, the sealing zone and the ruffled border, and vectorial transportation of intracellular vesicles in bone-resorbing osteoclasts. Here we show that Rab7, a small GTPase that is associated with late endosomes, is highly expressed and is predominantly localized at the ruffled border in bone-resorbing osteoclasts. The decreased expression of Rab7 in cultured osteoclasts by antisense oligodeoxynucleotides disrupted the polarization of the osteoclasts and the targeting of vesicles to the ruffled border. These impairments caused a significant inhibition of bone resorption in vitro. The results indicate that the late endocytotic pathway is involved in the osteoclast polarization and bone resorption and underscore the importance of Rab7 in osteoclast function.
在骨骼生长和重塑过程中，矿化的骨基质被破骨细胞通过持续向骨表面分泌质子和蛋白酶来进行吸收。这依赖于骨吸收破骨细胞中特殊质膜结构域（封闭区和皱褶缘）的形成以及细胞内囊泡的定向运输。在此我们表明，Rab7，一种与晚期内体相关的小GTP酶，在骨吸收破骨细胞中高表达且主要定位于皱褶缘。通过反义寡脱氧核苷酸降低培养破骨细胞中Rab7的表达，破坏了破骨细胞的极化以及囊泡向皱褶缘的靶向运输。这些损伤导致体外骨吸收显著受抑制。结果表明晚期内吞途径参与破骨细胞极化和骨吸收，并强调了Rab7在破骨细胞功能中的重要性。
