Multiple regulation of skeletal formation

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K11027
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Tsurumi University
• Principal Investigator: Nakashima Kazuhisa 鶴見大学, 歯学部, 講師 (90252692)
• Co-Investigator(Kenkyū-buntansha): 二藤 彰 鶴見大学, 歯学部, 教授 (00240747) ; 出野 尚 鶴見大学, 歯学部, 助教 (40435699)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 骨芽細胞 / 破骨細胞

Outline of Final Research Achievements

1)Annexin A5 (Anxa5) plays a critical role in the regulation of bone ridge outgrowth at enthesis. The sizes of bone ridges at the entheses of the long bones were increased in Anxa5 null mice. 8 weeks after hindlimb unloading, Anxa5 null mice showed a decrease in bone overgrowth to similar extents to wild-type mice, suggesting that Anxa5 regulates biological responses to mechanical forces. 2) Osterix (Osx) is a transcription factor that is necessary for osteoblast differentiation. Sirt7 null mice developed osteopenia characterized by decreased bone formation. Interaction of SIRT7 with OSX thorough C-terminal region results in activation of OSX activity. 3) Adenovirus-mediated gene transduction to osteoclast precursors inhibited osteoclast formation in vitro. Adenoviruses without a protein coding cDNA did not affect osteoclast formation, suggesting that modification protein production in osteoclast precursors has a negative impact on osteoclast formation.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

脊椎動物の骨形成過程には内軟骨性骨形成と内膜性骨形成の２つの異なる過程がある。両過程において骨芽細胞が骨基質の産生と石灰化と骨基質を溶解する破骨細胞の分化を制御する。骨芽細胞と破骨細胞の機能的平衡状態が破綻すると、骨粗鬆症、骨硬化症あるいは癌細胞の骨転移などの骨格病変を引き起こす。加えて、骨組織は靭帯と腱組織により筋肉組織と結合することにより機能的な動きを獲得して生理的な役割を果たす。本研究では骨芽細胞分化とenthesisの発達、並びに破骨細胞分化の制御機構に焦点を当てており、新たな知見を得た。この応用を目指すことによって、骨格と筋組織の調和のとれた成長とその障害が解明されると期待できる。