Purpose <p>Osteocytes are force-sensitive cells possessing a complex lacunar-canalicular system (LCS), embedded within a piezoelectric bone matrix. TRPV4, as a key mechanosensor, plays a crucial role in osteocyte mechanotransduction and related bone disorders. However, the mechanisms underlying its force sensing, mechanical signaling pathways, and biomechanical response remain poorly understood.</p> Methods <p>To address this issue, this study established a finite element model incorporating multiple mechanosensors—including bone matrix, LCS, osteocytes, and TRPV4—based on the piezoelectric effect. By integrating the multiphysics coupling of solid mechanics, fluid mechanics, and electric fields to simulate the complex effects on osteocytes, the model calculated stress, strain, and fluid shear stress (FSS) on TRPV4.</p> Results <p>Result indicate that piezoelectricity significantly increases stress and strain in TRPV4, particularly FSS. Biomechanical parameters of TRPV4 exhibit significant variations across different locations, with the highest stress levels observed at the cell processes (Maximum increase of approximately 300%). Stress distribution patterns also differ across distinct regions, while stress concentration in TRPV4 primarily occurs in its transmembrane domain and ion channel regions. This study reveals that upon coupling with primary cilia and RhoA, the mechanical response mechanism of TRPV4 undergoes significant alteration. TRPV4 exhibits greater sensitivity to fluid shear stress, whereas Piezo1 responds more strongly to membrane stress.</p> Conclusions <p>This study elucidates the microscopic mechanical response mechanism and gating activation mechanism of TRPV4 within complex bone cell environments. It clarifies the interaction mechanisms between TRPV4 and other cellular structures, providing a research pathway for understanding bone cell mechanical transduction mechanisms and complex interactions across multiple scales. This work offers theoretical insights into the pathogenesis and therapeutic approaches for TRPV4-related bone disorders.</p>

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Mechanobiological Response of Osteocyte TRPV4 Base on the Piezoelectricity of Bone Matrix

  • Shibo Gu,
  • Yuqing Duanwang,
  • Yinuo Zhao,
  • Shuo Gao,
  • Haochen Li,
  • Xinrui Wu,
  • Quanyou Zhang,
  • Yanru Xue,
  • Meng Zhang,
  • Xiaogang Wu,
  • Weiyi Chen

摘要

Purpose

Osteocytes are force-sensitive cells possessing a complex lacunar-canalicular system (LCS), embedded within a piezoelectric bone matrix. TRPV4, as a key mechanosensor, plays a crucial role in osteocyte mechanotransduction and related bone disorders. However, the mechanisms underlying its force sensing, mechanical signaling pathways, and biomechanical response remain poorly understood.

Methods

To address this issue, this study established a finite element model incorporating multiple mechanosensors—including bone matrix, LCS, osteocytes, and TRPV4—based on the piezoelectric effect. By integrating the multiphysics coupling of solid mechanics, fluid mechanics, and electric fields to simulate the complex effects on osteocytes, the model calculated stress, strain, and fluid shear stress (FSS) on TRPV4.

Results

Result indicate that piezoelectricity significantly increases stress and strain in TRPV4, particularly FSS. Biomechanical parameters of TRPV4 exhibit significant variations across different locations, with the highest stress levels observed at the cell processes (Maximum increase of approximately 300%). Stress distribution patterns also differ across distinct regions, while stress concentration in TRPV4 primarily occurs in its transmembrane domain and ion channel regions. This study reveals that upon coupling with primary cilia and RhoA, the mechanical response mechanism of TRPV4 undergoes significant alteration. TRPV4 exhibits greater sensitivity to fluid shear stress, whereas Piezo1 responds more strongly to membrane stress.

Conclusions

This study elucidates the microscopic mechanical response mechanism and gating activation mechanism of TRPV4 within complex bone cell environments. It clarifies the interaction mechanisms between TRPV4 and other cellular structures, providing a research pathway for understanding bone cell mechanical transduction mechanisms and complex interactions across multiple scales. This work offers theoretical insights into the pathogenesis and therapeutic approaches for TRPV4-related bone disorders.