Fluid flow induced calcium response in osteoblasts: mathematical modeling

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.