1999 Fiscal Year Final Research Report Summary
Effect of NaィイD1+ィエD1/CaィイD12+ィエD1 exchanger inhibitor on osteoclast formation and activation
| Project/Area Number |
10671749
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Showa University |
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Principal Investigator |
AMANO Hitoshi Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (90212571)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Keiko Showa University, School of Dentistry, Assistant Professor, 歯学部, 講師 (50119187)
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| Project Period (FY) |
1998 – 1999
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| Keywords | CSF-1 / osteoclast / NCX1 / PLCγ / KB-R7943 / osteoporosis / intracellular CaィイD12+ィエD1 / bone resorption / 骨粗鬆症 |
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| Research Abstract |
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.
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Research Products
(14 results)
