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A Fluorescent Intravital Imaging Approach to Study Load-Induced Calcium Signaling Dynamics in Mouse Osteocytes
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Fluid flow induced calcium response in osteoblasts: mathematical modeling.

J H Su1, F Xu, X L Lu

  • 1Biomedical Engineering and Biomechanics Center, School of Aerospace, Xi'an Jiaotong University, 710049 Xi'an, PR China.

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|June 14, 2011
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A new mathematical model simulates intracellular calcium ([Ca(2+)](i)) changes in osteoblasts due to fluid flow. It highlights extracellular ATP

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Area of Science:

  • Biomedical Engineering
  • Mechanobiology
  • Computational Biology

Background:

  • Fluid flow in bone's lacuno-canalicular network influences osteoblast intracellular calcium ([Ca(2+)](i)) levels, crucial for bone remodeling.
  • Mathematical modeling of this complex [Ca(2+)](i) response is challenging due to multiple regulatory factors.

Purpose of the Study:

  • To develop and validate a comprehensive mathematical model for osteoblast [Ca(2+)](i) response to fluid shear stress (SS).
  • To analyze the impact of experimental conditions like baseline [Ca(2+)](i) and ATP pretreatment on SS-induced [Ca(2+)](i) dynamics.

Main Methods:

  • Integrated major factors including ATP release, ion channels, and purinergic receptors into a mathematical model.
  • Simulated [Ca(2+)](i) responses under varying extracellular ATP concentrations and shear stress levels.
  • Quantitatively verified model predictions against published experimental data.

Main Results:

  • Extracellular ATP significantly impacts baseline [Ca(2+)](i) (73% increase with 0-10 μM ATP) more than SS (25% variation with 0-3.5 Pa SS).
  • ATP pretreatment alters the [Ca(2+)](i) response to SS compared to control conditions.
  • Relative [Ca(2+)](i) fluctuation is a more reliable indicator of response than absolute peak values.

Conclusions:

  • The developed model accurately captures osteoblast [Ca(2+)](i) dynamics under fluid shear stress.
  • Extracellular ATP plays a dominant role in setting the baseline [Ca(2+)](i) in osteoblasts.
  • The model can enhance experimental design and deepen understanding of osteoblast mechanotransduction.