2006 Fiscal Year Final Research Report Summary
CLCN7 POINT MUTANT INHIBITED Cl-EXTRUSION, RESUTLING IN OSTEOPETROSIS
| Project/Area Number |
17591957
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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 |
KAJIYA Hiroshi FUKUOKA DENTAL COLLEGE, FACULTY OF DENTISTRY, ASSISTANT PROFERSSOR, 歯学部, 助教 (80177378)
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| Co-Investigator(Kenkyū-buntansha) |
OKABE Koji FUKUOKA DENTAL COLLEGE, FACULTY OF DENTISTRY, PROFFESSOR, 歯学部, 教授 (80224046)
OKAMOTO Fujio FUKUOKA DENTAL COLLEGE, FACULTY OF DENTISTRY, LECTURE, 歯学部, 講師 (60153938)
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| Project Period (FY) |
2005 – 2006
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| Keywords | OSTEOCLAST / CLCN7 / Cl-CHANNEL / AUTOSOMAL OSTEOPETROSIS TYPE II / ACID ACTIVATION |
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| Research Abstract |
ClC7 Cl^- channels are crucial for osteoclastic bone resorption since they play an important role for acid secretion. Mice with a deficient ClC7 gene (CLCN7) have impaired osteoclastic Cl extrusion during bone resorption, resulting in severe osteopetrosis. It also has been reported that autosomal osteopetrosis type II (ADO II) results from heterozygous mutations in CLCN7. Although extracellular acidification is known to induce ClC7 Cl^- current in CLCN7 transfected oocytes, other characteristics of this acid-induced Cl^- current as well as effects of mutant CLCN7 in ADO II on osteoclastic Cl^- extrusion activity are unknown. The aim of present study was to characterize the ClC7 Cl^- currents cloned from mammalian osteoclasts and to clarify the effect of point mutations found in ADO II patients on Cl^- extrusion activity. Extracellular acidification (pH 6.0) evoked small native Cl^- currents in mouse osteoclasts. Transient expression of wild type human CLC7 in HEK293 cells induced significant Cl^- currents compared to mock-transfected cells. These acid-activated Cl^- currents were independent of intracellular acidification or [Ca^<2+>]i increase. In contrast, CLCN7 mutant gene expression in HEK293 cells did not display these acid-activated Cl currents. Furthermore, RAW 264.7 with the CLCN7 mutation at G215R demonstrated no change in osteoclast differentiation potential but a significant decrease in bone resorption activity compared to wild type CLCN7 expression. In summary, our results indicate that a CLCN7 mutation at the G215R locus associated with ADO II results in suppression of Cl extrusion activity during osteoclastic bone resorption.
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[Journal Article] α9β1 : A novel osteoclast integrin that regulates osteoclast formation and function.2006
Author(s)
Rao H, Lu G, Kajiya H, Garcia-Palacios V, Kurihara N, Anderson J, Partrene K, Sheppard D, Blair HC, Windle JJ, Choi SJ, Roodman GD
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Journal Title
Journal of Bone and Mineral Research 21巻10号
Pages: 1657-1665
Description
「研究成果報告書概要(和文)」より
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[Journal Article] A novel osteoclast integrin that regulates osteoclast formation and function.2006
Author(s)
Rao H, Lu G, Kajiya H, Garcia-Palacios V, Kurihara N, Anderson J, Partrene K, Sheppard D, Blair HC, Windle JJ, Choi SJ, Roodman GD: α9β1
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Journal Title
Journal of Bone and Mineral Research 27
Pages: 1657-1665
Description
「研究成果報告書概要(欧文)」より
