Mechanism of the regulation of osteoblast process formation by Runx2 through Tln2 regulation during osteoblast maturation

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18947
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Nagasaki University
• Principal Investigator: SAKANE Chiharu 長崎大学, 先導生命科学研究支援センター, 助教 (40792578)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 骨芽細胞突起形成 / Runx2 / Tln2

Outline of Final Research Achievements

Runx2 is an essential transcription factor for the differentiation of mesenchymal stem cells into osteoblasts. Runx2 is highly expressed in immature osteoblasts and the expression reduces during osteoblast maturation. In Runx2 transgenic mice under the control of 2.3 kb Col1a1 promoter, osteoblast maturation is inhibited, the number of osteocytes is reduced, the direction of collagen fibers is disturbed, and the number of processes in osteoblasts and osteocytes is reduced.
We identified Tln2 as a target gene of Runx2 in the regulation of osteoblast process formation. In this study, we generated Tln2 knockout mice and crossed them with Runx2 transgenic mice under the control of 2.3 kb Col1a1 promoter, and examined the involvement of Tln2 in the regulation of osteoblast process formation by Runx2.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

Tln2の生理的機能を明らかにした報告は少なく、骨芽細胞の分化・形態・機能および骨代謝に関する報告はない。本研究で Tln2ノックアウトマウスの骨組織を調べたところ、骨のコラーゲン繊維の走行にTln2が関与している可能性が示唆された。
また、骨芽細胞特異的にRunx2を過剰発現させたトランスジェニックマウスをTln2ノックアウトマウスと掛け合わせることによって、骨に見られる異常の一部が回復していた。得られた結果をもとに研究を発展させることは、Runx2による骨格形成制御の分子メカニズムの解明を進展させるとともに、骨の成熟を促進させる方法を提供し、骨代謝研究に大きく貢献する。