Fluid flow-induced soluble vascular endothelial growth factor isoforms regulate actin adaptation in osteoblasts

Area of Science:

• Bone Biology and Mechanobiology
• Cellular Mechanotransduction
• Osteoblast Signaling

Background:

• Mechanical signals are crucial for bone formation, mass maintenance, and structural integrity.
• Cellular mechanisms translating mechanical signals in bone cells remain incompletely understood.
• Vascular Endothelial Growth Factor (VEGF) is implicated in mechanosignaling pathways and actin reorganization.

Purpose of the Study:

• To investigate the hypothesis that fluid shear stress-induced VEGF up-regulation mediates actin cytoskeleton adaptation in osteoblasts during mechanotransduction.
• To elucidate the role of VEGF and its receptors in osteoblast response to pulsatile fluid shear stress (PFSS).

Main Methods:

• MC3T3-E1 osteoblast cells were exposed to pulsatile fluid shear stress (PFSS).
• VEGF and its receptor expression and secretion were analyzed.
• Effects of flow-conditioned medium, exogenous VEGF, and VEGF knockdown on actin stress fiber formation were assessed.
• Neutralizing antibodies against VEGF and its receptors were used to determine pathway involvement.

Main Results:

• PFSS significantly increased VEGF secretion from MC3T3-E1 cells.
• VEGF exposure or flow-conditioned medium induced stress fiber formation, while VEGF knockdown abrogated PFSS-induced actin polymerization.
• VEGF, particularly VEGF(164), acting via VEGFR-2 and NRP1, is critical for stress fiber formation during osteoblast mechanotransduction.

Conclusions:

• Flow-induced VEGF release regulates osteoblast actin adaptation during mechanotransduction.
• VEGF paracrine signaling facilitates communication between bone and endothelial cells.
• This pathway is essential for fracture healing, bone remodeling, and osteogenesis.