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Planar cell polarity aligns osteoblast division in response to substrate strain

Galea, GL; Meakin, LB; Savery, D; Taipaleenmaki, H; Delisser, P; Stein, GS; Copp, AJ; ... Price, JS; + view all (2015) Planar cell polarity aligns osteoblast division in response to substrate strain. Journal of Bone and Mineral Research , 30 (3) pp. 423-435. 10.1002/jbmr.2377. Green open access

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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 noncanonical 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. Heterozygous 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.

Type: Article
Title: Planar cell polarity aligns osteoblast division in response to substrate strain
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/jbmr.2377
Publisher version: http://dx.doi.org/10.1002/jbmr.2377
Language: English
Additional information: Copyright © 2014 The Authors. Journal of Bone and Mineral Research Published by American Society for Bone and Mineral Research. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Mechanical Strain, Osteoblasts, Planar Cell Polarity, Vangl2, Wnt Signaling, Animals, Cell Line, Cell Polarity, Cells, Cultured, Mice, Mutation, Nerve Tissue Proteins, Osteoblasts
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1450214
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