Development for low side effect anti-bone resorption medicines of pediatric steroidal osteoporosis

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11968
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Kyushu Dental College
• Principal Investigator: Maki Kenshi 九州歯科大学, 歯学部, 教授 (60209400)
• Co-Investigator(Kenkyū-buntansha): 松原 琢磨 九州歯科大学, 歯学部, 准教授 (00423137) ; 古株 彰一郎 九州歯科大学, 歯学部, 教授 (30448899) ; 青木 和広 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (40272603) ; 自見 英治郎 九州大学, 歯学研究院, 教授 (40276598)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 骨代謝 / 骨芽細胞 / 破骨細胞 / Bif-1 / Endophilin B1 / SH3GLB1

Outline of Final Research Achievements

Bif-1-deficient (Bif-1 -/- ) mice showed increased trabecular bone volume and trabecular number. Histological analyses indicated that the osteoclast numbers increased in Bif-1 -/- mice. Consistent with the in vivo results, osteoclastogenesis induced by RANKL was accelerated in Bif-1 -/- mice without affecting RANKL-induced activation of RANK downstream signals, such as NF-κB and MAPKs, CD115/RANK expression in osteoclast precursors, osteoclastic bone-resorbing activity and the survival rate. Unexpectedly, both the bone formation rate and osteoblast surface substantially increased in Bif-1 -/- mice. Osteoblastic differentiation and mineralization were enhanced in Bif-1 -/- mice. Finally, bone marrow cells from Bif-1 -/- mice showed a significantly higher colony-forming efficacy, suggesting that cells from Bif-1 -/- mice had higher clonogenicity and self-renewal activity than those from WT mice.

Free Research Field

小児歯科学、骨代謝

Academic Significance and Societal Importance of the Research Achievements

Bif-1欠損マウスでは骨梁の数と骨量が増加する。そのメカニズムが解明できたことにより、Bif-1をターゲットにした新たな骨代謝治療薬創出につながる可能性がある。