1999 Fiscal Year Final Research Report Summary
INHIBITORS FOR VACUOLAR THPE HィイD1+ィエD1-ATPaseINDUCES APOTOSIS IN OSTEOCLASTS
| Project/Area Number |
10671729
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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 |
Morphological basic dentistry
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| Research Institution | NATIONAL INSTITUTE OF INFECTIOUS DISEASES |
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Principal Investigator |
OKAHASHI Nobuo NATIONAL INSTITUTE OF INFECTIOUS DISEASES, DEPARTMENT OF ORAL SCIENCE SENIOR RESEARCHER, 口腔科学部, 主任研究員 (40150180)
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| Project Period (FY) |
1998 – 1999
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| Keywords | OSTEOCLAST / APOPTOSIS / PERIODONTITIS / CASPASE / LIPOPOLYSACCHARIDE / CYTOKINE |
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| Research Abstract |
Osteoclasts are multinucleated bone resorbing giant cells. Osteoclasts resorb bone minerals by acid. Production of acid by osteoclast is controlled by carbonic anhydrase and vacuolar type ATPase. Recently, we found that the inhibitors of vacuolar type ATPase trigger apoptotic cell death of osteoclasts. In this research project, we investigate the cellular mechanism of apoptotic events induced by the ATPase inhibitors.
Purified osteoclasts were prepared from mouse bone marrow cultures. Vacuolar type ATPase inhibitors, concanamycin A and bafilomycin induced cell death of purified osteoclast within 24 h. Hoechst stain and FITC-TUNEL revealed apoptotic features of this cell death of osteoclasts. Measurement of caspase activities revealed that ATPase inhibitors activated caspase-1 and caspase-3 during apoptotic events of osteoclasts. Furthermore, activation of caspase-8 and caspase-9 also detected. Fluorescenece labeling of osteoclastic mitochondorial membrene by MitAlert revealed that the mitochondoria membrane was destroyed by the ATPase inhibitors. These results suggested that vacuolar type ATPase plays an important role in bone resorption as well as survival of osteoclasts.
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