2003 Fiscal Year Final Research Report Summary
Regulatory mechanisms of proton extrusion in osteoclasts via RANKL-TRAF signal.
| Project/Area Number |
14571784
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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 | Fukuoka Dental College |
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Principal Investigator |
OKABE Koji Fukuoka Dental College, DENTISTRY, Professor (80224046)
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| Project Period (FY) |
2002 – 2003
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| Keywords | RANKL / osteoclas / H^+ extrusion / intracellular pH / H^+ pump / NHE / human odontoclast / OPG |
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| Research Abstract |
Although RANKL (receptor activator of NF-kB ligand) is well known to be the essential factorfor osteoclastgenesis, it remains unknown how RANKL regulates osteoclastic H^+ transporter in bone resorption. In this study, we examined effects of RANKL on H^+ extrusion activity in resorbing rat osteoclasts using intracellular pH (pHi) indicator, BCECF (2'7'-bis-(2-carboxyethyl)-5-carboxyfluorescein). Both basal pHi and H^+ extrusion activity in cultured resorbing osteoclasts, which were identified by forming the resorbing pits on calcium phosphate-coated quartz coverslips, were significantly both higher than those of non-resorbing osteoclasts. Pharmacological classification showed that resorbing osteoclasts expressed two types of H^+ -extruding systems : bafilomycin A_1- and amiloride-sensitive H^+ extrusion systems (vacuolar type proton pump (V-ATPase)-and Na^+ /H^+ exchanger (NHE)-mediated H^+ extrusion, respectively). RANKL increased both H^+ extrusion activities in mouse osteoclasts. On the other hand, pretreatment with osteoprotegerin (OPG : decoy receptor of RANKL) suppressed the RANKL-induced action.
These results indicate that RANKL up-regulates the intracellular H^+ production and activates the H^+ extrusion generated by V-ATPase and NHE. These mechanisms of H^+ transport by RANKL are likely to contribute to its regulation of bone resorption. Furthermore, we investigated the effects of RNKL in human odontoclasts (osteoclast-like cells) collected from human deciduous tooth. RANKL also promoted the bone resorption in human osteoclast-like cells, suggesting that human osteoclasts be useful in the following experiment system.
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Research Products
(14 results)
