2001 Fiscal Year Final Research Report Summary
Novel cell surface Fusion Regulartory Molecule involved in osteoclastogenesis: Morphological analysis of precursor fusion
| Project/Area Number |
12671775
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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 | KYUSHU UNIVERSITY |
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Principal Investigator |
KUKITA Toshio Kyushu University, Faculty of Dental Science, Associate professor, 大学院・歯学研究院, 助教授 (70150464)
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| Co-Investigator(Kenkyū-buntansha) |
KUKITA Akiko Saga Medical School, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30153266)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Membrane Fusion / Osteoclast / Adrenomedullin / Kat1 antigen / MFR / RAW cell clone / MIP1a |
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| Research Abstract |
Fine regulation of osteoclastogenesis is mediated through cell surface molecules expressed on osteoclast precursors. Lines of evidence suggest that peptides regulating the vascular system also modulate osteoclast differentiation and function. We have previously found a unique cell surface antigen (Kat1-antigen) expressed on rat osteoclasts, which is involved in the functional regulation of the calcitonin receptor (CTR). Here we show that adrenomedullin (ADM), a member of the calcitonin family peptides and a potent vasodilator, provoked a significant stimulation in osteoclastogenesis only in the presence of calcitonin but not in the absence of calcitonin. Such stimulatory effects mediated by ADM was disappeared by the addition of the anti-Kat1-Ag monoclonal antiboby (mAb Kat1). 125I -labelled ADM binding experiments demonstrated that specific receptors for ADM was detected in cultures for osteoclastogenesis and the binding of 125I-ADM was significantly inhibited by the addition of mAb Kat1. Further autoradiographic studies demonstrated that mononuclear precursors of osteoclasts expressed functional ADM receptor and specific binding of 125I-labelled ADM was markedly inhibited by mAb Kat1, suggesting a close relationship of the Kat1-Ag with the functional ADM receptor expressed on mononuclear osteoclast precursors. Specific ADM receptor was not detected on osteoclast-like multinucleated cells while these cells express a high level of Kat1-Ag. Modulation of osteoclastogenesis via ADM receptors is thought to be important in a fine regulation of osteoclast differentiation.
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