Planar cell polarity aligns osteoblast division in response to substrate strain

Area of Science:

• Biomechanical Engineering
• Cell Biology
• Skeletal Biology

Background:

• Bone adapts to mechanical loading through cellular and molecular reorganization.
• Osteoblast proliferation and organization are influenced by dynamic strain.
• Canonical Wnt signaling mediates the proliferative response to strain.

Purpose of the Study:

• To investigate the role of the Wnt/planar cell polarity (PCP) pathway in orienting osteoblast division in response to dynamic strain.
• To elucidate the interplay between canonical Wnt signaling and PCP in bone's response to biomechanical cues.

Main Methods:

• Exposure of osteoblast-like Saos-2 cells and mouse osteoblasts to dynamic substrate strain.
• Pharmacological blockade of Rho-associated coiled kinase (ROCK).
• Utilizing heterozygous loop-tail mutation in Vangl2 (a core PCP component).
• Micro-computed tomography (µCT) and scanning electron microscopy (SEM) of mouse bone architecture.

Main Results:

• Dynamic strain influences osteoblast division orientation independently of canonical Wnt signaling, through the noncanonical Wnt/PCP pathway.
• ROCK blockade prevents strain-induced orientation of osteoblast division.
• Impaired Vangl2 function in mouse osteoblasts disrupts strain-related division orientation.
• Vangl2 loop-tail heterozygous mice exhibit altered bone architecture and disorganized bone surfaces.

Conclusions:

• The Wnt/PCP pathway plays a critical role in orienting osteoblast division in response to mechanical strain, acting in parallel with canonical Wnt signaling.
• This pathway is active postnatally, contributing to skeletal adaptation to functional loading.
• The coordinated action of canonical Wnt and Wnt/PCP pathways fine-tunes bone architecture by regulating both the rate and orientation of osteoblast division.