Analysis on the spatiotemporal regulation of osteoclasts maturation via the osteocytic apoptosis

• Project/Area Number: 15K15537
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: The University of Tokyo
• Principal Investigator: Ikebuchi Yuki 東京大学, 医学部附属病院, 助教 (20645725)
• Research Collaborator: HONMA Masashi 東京大学, 医学部附属病院, 講師 (60401072)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 骨代謝 / 骨細胞 / 細胞間ネットワーク

Outline of Final Research Achievements

Using the established culturing system of primary osteocytes in collagen hydrogel, we analyzed on the regulatory mechanism of RANKL expression in apoptotic osteocytes induced by mechanical loading. As mimicking micro-cracks, hydrogels were cut by scalpel and osteocytes were collected in time- and distance-dependent manner. As a result, apoptosis was occurred and the elevation of RANKL expression was observed in osteocytes, especially located near the cutting section, as observed in mice in vivo model. These effects were suppressed in the presence of pan-caspase inhibitor. Furthermore, disturbing direct cell to cell communications using the porous membrane also showed the similar effect. These results indicated that any signals were transferred to neighboring cells from the apoptotic osteocytes through the direct cell to cell contact, and it would contribute to the efficient osteoclasts activation.

Research Products

• [Remarks] 東京大学医学部附属病院薬剤部試験研究室／臨床薬物動態学教室
  • URL: http://plaza.umin.ac.jp/~todaiyak/