Mechanical stress response of senescent osteocytes: an intercellular communication between bone resident cells mediated by specific secreted factors.

2024 Fiscal Year Final Research Report

• Project/Area Number: 22K09403
• 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: Kyushu University
• Principal Investigator: Uehara Norihisa 九州大学, 歯学研究院, 助教 (30368211)
• Project Period (FY): 2022-04-01 – 2025-03-31
• Keywords: osteocyte / senescence / mechanical stress

Outline of Final Research Achievements

In this study, we established a fluid shear stress model capable of generating physiological mechanical forces. Using this model, we applied mild exercise-equivalent shear stress (1 Pa, 1 Hz) to normal and senescent osteocytes. Transcriptomic analysis by RNA-seqrevealed the molecular responses to mechanical stimulation. We found that both normal and senescent osteocytes commonly upregulated genes related to growth factors, anti-inflammatory cytokines, and extracellular matrix components involved in wound healing. Additionally, conditioned media from both cell types following mechanical stimulation promoted myotune formation, suggesting that mechanically stimulated osteocytes may influence muscle regeneration even in a senescent state.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究では、力学的刺激に応答して分泌される骨細胞に特徴的な増殖因子、抗炎症サイトカイン、創傷治癒に関連する細胞外マトリクス分子の同定に成功するとともに、老化骨細胞においても、力学的刺激が筋組織に影響を及ぼす分泌因子の産生を誘導することを明らかにした。これらの結果は、高齢者における骨細胞への力学的刺激、すなわち適度な運動負荷が、筋量の維持や健康寿命の延伸に寄与する可能性を示唆している。さらに、加齢に伴い蓄積し、加齢関連疾患の進展に関与するとされる老化細胞であっても、力学的刺激に対する応答性を保持しており、一定の生理的意義を有する可能性が示された。