[Zoledronate inhibits TRPV5 and NFATc1 expression during differentiation of osteoclasts]

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).

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.

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).

ZOL can significantly inhibit osteoclastogenesis and bone resorption, which may be attributed, at least partly, to ZOL-induced inhibition of TRPV5 and NFATc1 expressions.