2013 Fiscal Year Final Research Report
Subcellular behavior of RANKL in osteocytes
Project/Area Number |
24890048
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Single-year Grants |
Research Field |
Orthopaedic surgery
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Research Institution | The University of Tokyo |
Principal Investigator |
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Project Period (FY) |
2012-08-31 – 2014-03-31
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Keywords | 骨代謝 / 骨細胞 / 破骨細胞活性化 / RANKL / 骨粗鬆症 |
Research Abstract |
Although the significance of RANKL expressed in osteocytes has been elucidated very recently, the detailed mechanisms behind it remained unclear. We have approached this by constructing a culture system which enables long term culture of osteocytes without losing their properties. Analyses based on this system have reveled that the direct cell-to-cell contact between osteocytes and osteoclast progenitor cells plays crucial roles in osteoclastogenesis. It has been also elucidated that OPG expressed in osteocytes regulates RANKL lysosomal sorting and that stimulation-triggered RANKL release from lysosome in osteocytes is key to efficient osteoclastogenesis. These study outcomes are marked in that the critical role of live osteocytes was unraveled while osteocyte death had been shown to induce osteoclastognesis previously. Furthermore, these findings have enhanced and will potentially promote the understanding of bone homeostasis and its related disorders.
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