Khadeer Mohammed A, Sahu Surasri N, Bai Guang, Abdulla Sunia, Gupta Anandarup
Department of Biomedical Sciences, Dental School, University of Maryland, 666 West Baltimore Street, Baltimore, MD 21201, USA.
Bone. 2005 Sep;37(3):296-304. doi: 10.1016/j.bone.2005.04.035.
Zinc has been previously demonstrated to be a potent inhibitor of osteoclastogenesis and osteoclast function. The mechanisms for cellular uptake of zinc into osteoclasts have not been characterized. We have corroborated previous studies on the reduction of osteoclastogenesis in the presence of extracellular zinc. We demonstrate that osteoclasts express a ubiquitous plasma membrane zinc transporter, namely ZIP1, which was diffusely distributed throughout the cytoplasm. Following an adenoviral-mediated overexpression of ZIP1 in murine osteoclasts, ZIP1 was predominantly colocalized with actin at the sealing zone and significantly inhibited osteoclast function, as assessed by resorptive activity. Finally, overexpression of ZIP1 negatively impacted NF-kappaB binding activity, as assessed by electrophoretic mobility shift assays. In conclusion, these data both corroborate previous studies on regulation of osteoclast formation and activity by zinc and reveal the presence of a zinc uptake mechanism that exerts an important effect on osteoclast activity.
锌先前已被证明是破骨细胞生成和破骨细胞功能的有效抑制剂。锌进入破骨细胞的细胞摄取机制尚未明确。我们证实了先前关于细胞外锌存在时破骨细胞生成减少的研究。我们证明破骨细胞表达一种普遍存在的质膜锌转运体，即ZIP1，它在整个细胞质中呈弥散分布。在小鼠破骨细胞中通过腺病毒介导ZIP1过表达后，ZIP1主要在封闭区与肌动蛋白共定位，并通过吸收活性评估显著抑制破骨细胞功能。最后，通过电泳迁移率变动分析评估，ZIP1过表达对核因子κB结合活性产生负面影响。总之，这些数据既证实了先前关于锌对破骨细胞形成和活性调节的研究，又揭示了一种对破骨细胞活性有重要影响的锌摄取机制的存在。
