2023 Fiscal Year Final Research Report

Control of Mechano-signalling Evoked by Hydrostatic Pressure and Its Application to Tissue Engineering

Research Project

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Project/Area Number	19H01173
Research Category	Grant-in-Aid for Scientific Research (A)
Allocation Type	Single-year Grants
Section	一般
Review Section	Medium-sized Section 90:Biomedical engineering and related fields
Research Institution	The University of Tokyo
Principal Investigator	Ushida Takashi 東京大学, 大学院工学系研究科(工学部), 名誉教授 (50323522)
Co-Investigator(Kenkyū-buntansha)	上田太郎早稲田大学, 理工学術院, 教授 (90356551) 古川克子東京大学, 大学院工学系研究科(工学部), 准教授 (90343144) 伊藤弓弦筑波大学, 生命環境系, 教授 (30500079) 佐藤正人東海大学, 医学部, 教授 (10056335)
Project Period (FY)	2019-04-01 – 2023-03-31
Keywords	軟骨細胞 / 静水圧
Outline of Final Research Achievements	Hydrostatic pressure is known one of the physical stimulations which are physiologically loaded to articular chondrocytes. This research tried to verify which kinds of intracellular signals are evoked by hydrostatic pressure loading, then how gene expressions are changed, and how hydrostatic pressure loading promotes articular cartilage regeneration. For those purposes, we tried to verify whether Ras might be activated by hydrostatic pressure in vitro conditions, then we found the possibility that Ras itself is activated without any upper stream signals. Additionally, we found gene families (mRNA, miRNA, lincRNA) responding to hydrostatic pressure loading through transcriptome analysis. Then, we developed a system where chondrocytes can be simultaneously loaded with hydrostatic pressure and compressive stress. The system could design quasi-optimal conditions of physical stimulations adequate for articular cartilage regeneration.
Free Research Field	バイオメカニクス
Academic Significance and Societal Importance of the Research Achievements	物理刺激が細胞に及ぼす影響については，特にずり応力，引っ張り応力について多く研究されてきており，血管内皮細胞，血管平滑筋細胞，骨芽細胞，筋芽細胞などで多くの成果が出ている．一方，静水圧刺激については，MPaオーダー負荷システムを構築することの困難さなどから，研究論文も少ないと言った背景がある．その中で本研究が明らかにした静水圧刺激に対する軟骨細胞の応答の，シグナルレベル，遺伝子発現レベルそして組織再生レベルでの知見は，この分野の研究の発展を促進させる学術的な意味を持つ．また我が国だけでも一千万人オーダーで罹患している変形性関節症治療の新たな指針の一つとなり得る意味での社会的意義がある．