Investigation of small molecule compounds for hypophosphatasia

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17333
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Shimane University
• Principal Investigator: Takahashi Tomoo 島根大学, 医学部, 特別協力研究員 (10624934)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 低ホスファターゼ症 / 間葉系幹細胞 / 遺伝子発現プロファイル

Outline of Final Research Achievements

Comprehensive genetic expression analysis using mesenchymal stem cells and osteoblasts derived from patients with hypophosphatasia (HPP) revealed that not only bone and cartilage differentiation, but also DNA replication, cell cycle, nucleic acid metabolism such as RNA metabolism and ribosome biosynthesis fluctuated. We also identified that genetic profile of HPP were involved in several biological processes including extracellular matrix, embryonic development, keratin metabolism, skeletal remodeling, relaxin　signaling pathways, and Wnt signaling pathways. The target route of the therapeutic drug has not yet been identified, but we plan to further investigate it in the future together with the results of metabolome analysis.

Free Research Field

先天代謝異常

Academic Significance and Societal Importance of the Research Achievements

これまで重症HPPの間葉系幹細胞（MSC）および骨芽細胞(Ost)に関する網羅的遺伝子発現解析は国内外で行われていない。今回、HPPのMSCとOstが骨分化・軟骨分化以外の生物学的プロセスに関与していること、そして、ALPが細胞外で働く酵素として考えられていたが、ALPが多くの細胞内機能に影響を及ぼしていることを明らかにできたことはHPPだけでなくALPが関与する多くの疾患において学術的な意義が高いと思われる。