Planar Cell Polarity Aligns Osteoblast Division in Response to Substrate Strain

Gabriel Galea, Lee B Meakin, Dawn Savery, Hanna Taipaleenmaki, Peter J Delisser, Gary Stein, Andrew Copp, Andre van Wijnen, Lance E Lanyon, Joanna Price

Research output: Contribution to journalArticle (Academic Journal)peer-review

14 Citations (Scopus)
311 Downloads (Pure)

Abstract

Exposure of bone to dynamic strain increases the rate of division of osteoblasts and also influences the directional organization of the cellular and molecular structure of the bone tissue that they produce. Here we report that brief exposure to dynamic substrate strain (sufficient to rapidly stimulate cell division) influences the orientation of osteoblastic cell division. The initial proliferative response to strain involves canonical Wnt signaling and can be blocked by sclerostin. However, the strain-related orientation of cell division is independently influenced through the non-canonical Wnt/planar cell polarity (PCP) pathway. Blockade of Rho-associated coiled kinase (ROCK), a component of the PCP pathway, prevents strain-related orientation of division in osteoblast-like Saos-2 cells. Heterozyogous loop-tail mutation of the core PCP component van Gogh-like 2 (Vangl2) in mouse osteoblasts impairs the orientation of division in response to strain. Examination of bones from Vangl2 loop-tail heterozygous mice by μCT and scanning electron microscopy reveals altered bone architecture and disorganized bone-forming surfaces. Hence, in addition to the well accepted role of PCP involvement in response to developmental cues during skeletal morphogenesis, our data reveal that this pathway also acts postnatally, in parallel with canonical Wnt signaling, to transduce biomechanical cues into skeletal adaptive responses. The simultaneous and independent actions of these two pathways appear to influence both the rate and orientation of osteoblast division thus fine-tuning bone architecture to meet the structural demands of functional loading.
Original languageEnglish
Article number2377
Pages (from-to)423-435
Number of pages13
JournalJournal of Bone and Mineral Research
Volume30
Issue number3
DOIs
Publication statusPublished - 16 Feb 2015

Bibliographical note

Date of Acceptance: 10/09/2014

Keywords

  • OSTEOBLASTS
  • PLANAR CELL POLARITY
  • WNT SIGNALING
  • MECHANICAL STRAIN
  • VANGL2

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