Stepwise increasing and decreasing fluid shear stresses differentially regulate the functions of osteoblasts

Area of Science:

• Biomaterials Science
• Cell Biology
• Mechanobiology

Background:

• Osteoblasts are known to respond to fluid shear stress (FSS), but their perception of slow temporal changes in FSS remains unclear.
• In vivo studies show bone mineral density changes with training intensity, suggesting a role for temporal FSS gradients.

Purpose of the Study:

• To investigate if osteoblasts can detect and differentially respond to temporal gradients of FSS.
• To test the hypothesis that increasing FSS inhibits osteoclastogenesis and enhances anabolic responses, while decreasing FSS has opposite effects.

Main Methods:

• Primary osteoblasts were subjected to stepwise increasing or decreasing FSS at varying magnitudes and durations.
• Osteogenic (alkaline phosphatase, calcium deposition) and resorption (RANKL/OPG gene expression) markers were analyzed.

Main Results:

• Stepwise increasing FSS (5 dyn/cm²) significantly decreased RANKL/OPG gene expression, while decreasing FSS increased it.
• Both increasing and decreasing FSS enhanced alkaline phosphatase expression and calcium deposition.
• A higher FSS temporal gradient showed similar, but less pronounced, effects on anabolic markers, with decreasing FSS slightly inhibiting them.

Conclusions:

• Osteoblasts can detect slow temporal gradients of FSS in a dose-dependent manner.
• These differential responses may explain in vivo bone mineral density changes observed with gradual exercise.
• Stepwise FSS provides a valuable model for studying bone cell adaptation to mechanical loading and unloading.