Analysis of the function of CTNNBL1 in osteoblast differentiation

• Project/Area Number: 18K09111
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kagoshima University
• Principal Investigator: Kawamura Ichiro 鹿児島大学, 医歯学域鹿児島大学病院, 助教 (90535832)
• Co-Investigator(Kenkyū-buntansha): 前田 真吾 鹿児島大学, 医歯学総合研究科, 特任准教授 (60353463) ; 永野 聡 鹿児島大学, 医歯学域医学系, 教授 (50373139) ; 瀬戸口 啓夫 鹿児島大学, 医歯学総合研究科, 客員研究員 (40423727)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: CTNNBL1 / CDC5L / 骨芽細胞分化 / 軟骨細胞分化 / WNTシグナル / BMPシグナル

Outline of Final Research Achievements

We initially analyzed the function of CTNNBL1 in osteochondrogenic differentiation, but the phenotype was not reproducible, so we proceeded to analyze the function of its binding partner CDC5L. In a series of analyses, CDC5L was found to promote early chondrogenic differentiation and inhibit osteoblast differentiation. In addition, CDC5L may inhibit the differentiation of undifferentiated mesenchymal cells into tendons and ligaments. These results suggest that CDC5L may be a molecular switch from osteochondral progenitor cells to chondrocyte differentiation. It was suggested that it may play an important role in the initial ligamentous cartilage degeneration during the ossification process, or in the chondrocyte differentiation of interstitial and vascular cells.

Academic Significance and Societal Importance of the Research Achievements

Catenin-beta-like 1(CTNNBL1)との結合パートナーであるCDC5L (cell division cycle 5-like)遺伝子は脊椎後縦靭帯骨化症(OPLL)患者のゲノムワイド関連解析で得られた疾患感受性領域の候補遺伝子群の１つである。それぞれの間葉系幹細胞の分化選別スイッチとして、軟骨細胞を選別する役割を解明することで、内軟骨性骨化のメカニズムの1つを明らかにし、特に脊柱靭帯骨化症の病態解明の手掛かりの一助となりえる結果である。

Research Products

• [Journal Article] BMP-induced Atoh8 attenuates osteoclastogenesis by suppressing Runx2 transcriptional activity and reducing the Rankl/Opg expression ratio in osteoblasts (2020)
  • Author(s): Yahiro Yuhei、Maeda Shingo、Morikawa Masato、Koinuma Daizo、Jokoji Go、Ijuin Toshiro、Komiya Setsuro、Kageyama Ryoichiro、Miyazono Kohei、Taniguchi Noboru
  • Journal Title: Bone Research Volume: 8 Issue: 1 Pages: 32-32
  • DOI: 10.1038/s41413-020-00106-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Examining cartilage metabolism in regard to TGF-b/BMP signaling and spinal ligament ossification (2021)
  • Author(s): 前田真吾
  • Organizer: 第33回日本軟骨代謝学会
• [Presentation] CDC5L, a genetically associated gene of the Ossification of the Posterior Longitudinal Ligamen of the Ossification of the Posterior Longitudinal Ligament(OPLL) is expressed (2020)
  • Author(s): Go Jokoji, Shingo maeda, Ichiro Kawamura
  • Organizer: Orthopaedic Research Society Annual Meeting 2020
  • Int'l Joint Research
• [Presentation] 脊椎後縦靭帯骨化症原因候補遺伝子CDC5Lの機能解析 (2019)
  • Author(s): 城光寺豪 前田真吾 河村一郎
  • Organizer: 第３４回日本整形外科学会基礎学術集会
• [Book] OPLL Ossification of the Posterior Longitudinal Ligament (2020)
  • Author(s): Okawa A, Matsumoto M, Iwasaki M, Kawaguchi Y Editors (pp39-46. Maeda S, Kawamura I, Tominaga H, Taniguchi N)
  • Total Pages: 278
  • Publisher: Springer