Abstract: Objective To explore the effect of zoledronate (ZOL) on osteoclast differentiation and expressions of transient
receptor potential vanilloid 5 channel (TRPV5) and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). Methods
RAW264.7 cells were divided into two groups for treatment with RANKL for 5 days (group A) or with additional ZOL
treatment in the last 2 days of RANKL treatment (group B). Osteoclastogenesis of the cells and the mRNA and protein
expressions of TRPV5 and NFATc1 after the treatments were examined. Results In group B, the number of newly generated
osteoclasts (≥3 nuclei), number and size of dentin resorption lacunaes were 29.0 ± 2.4, 24.8 ± 1.1, and 2 030.0 ± 165.7 μm2,
respectively, which were significantly lower than those in group A (56.5±4.5, 49.3±0.9, and 3 946.7±367.5 μm2, respectively, P<
0.01). Fluorescent intensity of TRPV5 and NFATc1 were also significantly decreased in group B (P<0.01). Compared with those
in group A, TRPV5 mRNA and protein expressions in group B were down-regulated by 50.4% and 37.8%, and those of NFATc1
by 68.0% and 48.4%, respectively (P<0.01). Conclusion ZOL can significantly inhibit osteoclastogenesis and bone resorption,
which may be attributed, at least partly, to ZOL-induced inhibition of TRPV5 and NFATc1 expressions.