Expression of the zinc transporter ZIP1 in osteoclasts.

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.