| Project/Area Number |
09672094
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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 |
矯正・小児・社会系歯学
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| Research Institution | The University of Tokushima |
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Principal Investigator |
MORIYAMA Keiji The University of Tokushima, School of Dentistry, Professor, 歯学部, 教授 (20262206)
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| Co-Investigator(Kenkyū-buntansha) |
BABA Yoshiyuki Tokyo Medical and Dental University, School of Dentistry, Research Associate, 歯学部, 助手 (70251535)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | mechanical stress / IL-6 / soluble IL-6receptor / gp130 / MAP kinase / JAK-STAT / osteoblast / メカニカメストレス / 歯根膜細胞 / 力学的刺激 / チロシンリン酸化 / src |
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| Research Abstract |
Studies on interleukin-6 (IL-6) in bone metabolism in response to mechanical stress have been accumulating. However, its effects on osteoblasts are still unclear because the results are conflicting depending on the study models employed. We reasoned that these conflicting data are due to variable expression levels of membrane-bound IL-6 receptors (IL-6Rs). In the present study, we found that IL-6 in combination with soluble IL-6R (sIL-6R) consistently caused a marked elevation of alkaline phosphatase and a decrease in proliferation in the human osteoblastic cell line MG-63, which expressed no detectable membrane-bound IL-6R and failed to respond to IL-6. These effects of IL-6/sIL-6R were blocked by neutralizing antibodies to the IL-6 signal transducer gp 130, suggesting an involvement of IL-6 signaling in the elicitation of the effects of IL-6/sIL6R.Upon stimulation with IL-6/sIL-6R, the gp 130, cytoplasmic Janus kinases JAK1 and JAK2 were tyrosine phosphorylated. Moreover, signal transducers and activators of transcription STAT1 and STAT3 were also tyrosine phosphorylated, translocated to the nucleus, and bound to the putative STAT-binding DNA elements. In addition, mitogen-activated protein (MAP) kinase was also activated in response to IL-6/sIL-6R.These data demonstrate that sIL-SR may enhance the responsiveness of MG-63 cells to IL-6. Thus, IL-6 in collaboration with sIL-6R may modulate differentiation and proliferation of osteoblastic cells, presumably by activating two distinct signaling pathways of JAK-STAT and MAP kinase.
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