Bisphosphonates (BPs) reduce bone pain and fractures by balancing the osteoblast/ osteoclast ratio. The behavior of ion channels in the presence of BPs is not known. To investigate this, the effect of zoledronic acid BP (ZOL) (3 × 10 −8 to 5 × 10 −4 M) treatment, on ion channels, cell proliferation, and mineralization, has been investigated on preosteoclast-like cells, RAW264.7, preosteoblast-like cells MC3T3-E1, and rat/mouse native bone marrow-derived osteoblasts. In whole-cell patch clamp on cell line-and bone marrow-derived osteoblasts, ZOL potentiated outward currents. On RAW264.7, ZOL (10 −4 M)-evoked current was reduced by the Kv channel blocker tetraethylammonium hydrochloride (TEA), but not by the selective TRPV1-channel antagonist capsazepine. On MC3T3-E1 cells and bone marrow-derived osteoblasts, ZOL-evoked current (5 × 10 −8 to 10 −4 M) was reduced by capsazepine, whereas the selective TRPV1-channel agonist capsaicin potentiated the control current. In the cell proliferation assay, 72 h incubation of RAW264.7 and MC3T3-E1 cells with ZOL reduced proliferation, with IC 50 values of 2.62 × 10 −7 M and 2.02 × 10 −5 M, respectively. Mineralization of MC3T3-E1 cells and bone marrow-derived osteoblasts was observed in the presence of capsaicin and ZOL (5 × 10 −8 –10 −7 M); ZOL effects were antagonized by capsazepine. In summary, the ZOL-induced activation of TRPV1 channel mediates the mineralization of osteoblasts and counterbalances the antiproliferative effects, increasing the IC 50 . This mechanism is not operative in osteoclasts lacking the TRPV1 channel.
|Titolo:||Zoledronic acid modulation of TRPV1 channel currents in osteoblast cell line and native rat and mouse bone marrow-derived osteoblasts: Cell proliferation and mineralization effect|
TRICARICO, Domenico (Corresponding)
|Data di pubblicazione:||2019|
|Appare nelle tipologie:||1.1 Articolo in rivista|