Role of YAP/TAZ mechanotransduction in 3D culture clumps of MSCs/ECM complexes

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K17351
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Periodontology
• Research Institution: Hiroshima University
• Principal Investigator: Kajiya Mikihito 広島大学, 医系科学研究科(歯), 助教 (00633041)
• Research Collaborator: Komatsu Nao
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 間葉系幹細胞 / C-MSCs / YAP/TAZ / メカノトランスダクション

Outline of Final Research Achievements

Floating culture clumps of MSCs/ECM complexes (C-MSCs) consist of cells and self-produced ECM. Previous studies have demonstrated that C-MSCs can be transplanted into bony lesions without an artificial scaffold to induce bone regeneration.　Moreover, osteoinductive medium (OIM)-treated C-MSCs (OIM-C-MSCs) have shown rapid and increased new bone formation in vivo. To apply C-MSCs for novel cell therapy, their cellular properties at the molecular level must be elucidated. This study investigated the role of YAP/TAZ mechanotransduction in C-MSCs/OIM-C-MSCs.
C-MSCs cultured in floating conditions lost their actin cytoskeleton to down-regulate YAP/TAZ activity, which directed cells to undergo adipogenesis/chondrogenesis. OIM treatment induced abundant COL1 deposition, which facilitated Intβ1-dependent actin fiber formation and YAP/TAZ activity in C-MSCs. Importantly, elevation of YAP/TAZ activity via OIM was associated with COL1 deposition, suggesting a positive feedback loop in OIM-C-MSCs.

Free Research Field

歯周治療

Academic Significance and Societal Importance of the Research Achievements

これまでに骨分化誘導を施したC-MSCsの移植が、人工材料を用いたMSCsの移植と比較して効果的に歯周組織再生を促進することが示されていた。本研究の成果によって、C-MSCsの細胞性質がメカのトランスダクションの観点から明らかになったことは、臨床応用のための科学的根拠の取得につながると期待できる。
さらに、本研究で発見されたC-MSCsにおけるYAP/TAZメカノトランスダクションの意義を応用し、in vitroでC-MSCsから骨様組織を作製できる可能性が示されたことは、より効果的な骨再生医療の開発に貢献できる可能性が高い。