Effect of NaィイD1+ィエD1/CaィイD12+ィエD1 exchanger inhibitor on osteoclast formation and activation

Na - D1+ D1/Ca - D12+ D1 exchanger (NCX) catalyzes the electrogenic exchange of 3na - D1+ D1 for 1Ca D12+ D12 across the plasma membrane in many mammalian cells. We已预先报告the Na - D1+ c - D12+ c - D1 exchange activity had an important role for CSF-1-induced osteoclastdifferentiation. In the present study，我们尝试确认the role of NCX1，one of the isoforms of NCX and imports Ca into the cells from extracellular in the reversemode,in osteoclast differentiation.osteoclast formation was studied in mouse bone marrow cells culturedfor 6-day in the presence of sRANKLigand and CSF-1, Treatment with KB-R7943, a new NCX1 inhibitor，不只是blocked the reverse mode of NCX1 activity，但也有osteoclast differentiation and boneresorption induced by CSF-1. It also dose-dependently inhibited Na - D1+ D145 -dependent - D1Cauptake In mature osteoclasts. However, Ouabaina Na - D1+ D1K - D1ATPase inhibitor stimulated osteoclast form . in addition，NCX1 antisense oligodeoxynucleotide (ODN) reduced the number of tartrate-resistant acidphosphatase-positive multinucleated cells and decreased the amount of NCX1，while non-sense or mismatched ODN did not.In conclusion，the activation of NCX1是CSF-1-induced osteoclast differentiation。

NaィイD1+ィエD1/CaィイD12+ィエD1 exchanger (NCX) catalyzes the electrogenic exchange of 3 NaィイD1+ィエD1 for 1 CaィイD12+ィエD1 across the plasma membrane in many mammalian cells. We have previously reported that the NaィイD1+ィエD1/CaィイD12+ィエD1 exchange activity had an important role for CSF-1-induced osteoclast differentiation. In the present study, we sought to confirm the role of NCX1, one of the isoforms of NCX and imports CaィイD12+ィエD1 into the cells from extracellular in the reverse mode, in osteoclast differentiation.Osteoclast formation was studied in mouse bone marrow cells cultured for 6-day in the presence of sRANKLigand and CSF-1, Treatment with KB-R7943, a new NCX1 inhibitor, not only blocked the reverse mode of NCX1 activity but also the osteoclast differentiation and bone resorption induced by CSF-1. It also dose-dependently inhibited NaィイD1+ィエD1-dependent ィイD145ィエD1Ca uptake In mature osteoclasts. However, Ouabain, a NaィイD1+ィエD1KィイD1+ィエD1ATPase inhibitor stimulated osteoclast formation.In addition, NCX1 antisense oligodeoxynucleotide (ODN) reduced the number of tartrate-resistant acid phosphatase-positive multinucleated cells and decreased the amount of NCX1, while non-sense or mismatched ODN did not.In conclusion, the activation of NCX1 is essential for CSF-1-induced osteoclast differentiation.