Development of therapeutic approach and exploration of molecules activating the central and peripheral organ for the treatment of musculoskeletal disorders

• Project/Area Number: 17H04409
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Saitama Medical University
• Principal Investigator: Sato Tsuyoshi 埼玉医科大学, 医学部, 准教授 (60406494)
• Co-Investigator(Kenkyū-buntansha): 臼井 通彦 九州歯科大学, 歯学部, 准教授 (10453630) ; 古株 彰一郎 九州歯科大学, 歯学部, 教授 (30448899) ; 有吉 渉 九州歯科大学, 歯学部, 教授 (40405551)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000); Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: Auts2 / 骨芽細胞 / コンディショナルノックアウトマウス / Tas1R3 / 神経細胞 / 骨 / 神経 / 自閉症 / 骨形成促進薬 / Tas1r3 / 骨芽細胞特異的 / 遺伝子 / 脳 / 遺伝子導入 / 運動器疾患 / 超音波

Outline of Final Research Achievements

In this study, AUTS2 gene which is expressed by neurons was upregulated during osteoblast differentiation. In AUTS2-knock out osteoblasts, Runx2 expression was downregulated by adding BMP and the calcification was inhibited. We generated osteoblasts-specific AUTS2-deficient mice and found that bone volume was decreased in these mice. Under the non-contact co-culture, Schwann cells and osteocytes differentiate each other via humoral factors. Moreover, we showed that the calcification was inhibited in mesenchymal stem cells derived from Tas1r3 knock out mice.

Academic Significance and Societal Importance of the Research Achievements

神経系と骨代謝は密接に関係していると考えられている。本研究では、AUTS2という神経系で豊富に発現している遺伝子が、骨組織においても発現が高いことを見出しており、骨分化に伴い発現が上昇したことを、in vitro実験で発見した。また、in vivoにおいても、骨特異的にAUTS2遺伝子を欠失させたノックアウトマウスの骨量が低下していた。これらのことから、AUTS2は骨組織において重要な役割を果たしていると考えられる。神経系で重要な分子が骨代謝にも重要であることから、神経系疾患と骨代謝疾患の病態解明に寄与する研究であり、学術的意義は大きい結果をもたらすと思われる。

Research Products

• [Journal Article] Vascular endothelial growth factor-D upregulation in mesenchymal stem cells derived from melanocortin 2 receptor-deficient mice during osteoblast differentiation (2022)
  • Author(s): Yuki Takaku, Ko Ito, Dai Chida, Tsuyoshi Sato
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: in press
  • Peer Reviewed
• [Journal Article] Soluble factors mediate the interaction between Schwann cells and osteocytes (2020)
  • Author(s): Eiji Ikami, Tsuyoshi Sato, Taketo Tomoda, Yosuke Fukushima, Shoichiro Kokabu, Tetsuya Yoda
  • Journal Title: Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology Volume: in press Issue: 5 Pages: 394-399
  • DOI: 10.1016/j.ajoms.2019.12.004
  • Peer Reviewed / Int'l Joint Research