Examination of bone regeneration in cleft palate using RANKL binding peptide

• Project/Area Number: 16K20419
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: KATO Genki 東京医科歯科大学, 歯学部, 非常勤講師 (00770231)
• Research Collaborator: AOKI Kazuhiro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 非侵襲的骨再生 / RANKL結合ペプチド / BMP-2 / ゼラチンハイドロゲル / 粒子状担体 / 注射 / 上顎骨骨造成 / ペプチド / 注射による骨造成法 / ＢＭＰ－２ / 骨形成促進ペプチド / 骨造成 / 上顎骨 / 骨形成 / 口蓋裂

Outline of Final Research Achievements

We investigated the time-course study after the injection of bone formation materials toward the application of a bone-reconstruction method to the cleft-palate patients. The gelatin hydrogel, the carrier of bone formation materials, was provided from the department of regeneration science and engineering of biomaterials, Institute for frontier medical sciences, Kyoto University. The thickness of the maxilla bone in 8-week-old male mice did not increase by an injection of BMP-2 incorporated with the carrier, but it increased by BMP-2 with RANKL-binding peptide. The bone mineral density was increased gradually in 7 weeks after the injections even when we used granule type of carrier whose diameter was less than 20 μm. The bone mineral density of basal bone (mouse maxilla) after the injection of bone-forming material was significantly higher when compared to the non-injection case.

Academic Significance and Societal Importance of the Research Achievements

本研究は日々の歯科医療に必要な骨造成法の開発であり、特に幼い頃から何度も観血処置をしなければならない口蓋裂患者の非侵襲的な骨造成法の開発につながる研究でもある。本研究により、手術をせずに注射で骨を増やす方法が発展した。経時的な骨の成熟度合いが明らかとなったことにより、注射法の臨床応用に期待が高まった。また、局所の骨形成促進剤であるBMP-2では不可能であった足場材料よりも厚みのある骨を造成することをRANKL分子に結合するペプチドの添加により可能にした。そのペプチドの骨形成促進メカニズムは、我々が2018年にNatureに掲載された新たな骨形成メカニズムにより説明でき、学術的にも意義がある。

Research Products

• [Journal Article] Coupling of bone resorption and formation by RANKL reverse signalling. (2018)
  • Author(s): Ikebuchi Y, Aoki S, Honma M, Hayashi M, Sugamori Y, Khan M, Kariya Y, Kato G, Tabata Y, Penninger JM, Udagawa N, Aoki K, Suzuki H
  • Journal Title: Nature Volume: 561 Issue: 7722 Pages: 195-200
  • DOI: 10.1038/s41586-018-0482-7
  • Peer Reviewed / Open Access / Int'l Joint Research