Blocking mechanosensitive ion channels eliminates the effects of applied mechanical loading on chick joint morphogenesis
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Supporting information
Published version
Author(s)
Nowlan, NC
Parisi, Cristian
Chandaria, Vikesh
Type
Journal Article
Abstract
Abnormalities in joint shape are increasingly considered a critical risk factor for developing osteoarthritis in life. It has been shown that mechanical forces during prenatal development, particularly those due to fetal movements, play a fundamental role in joint morphogenesis. However, how mechanical stimuli are sensed or transduced in developing joint tissues is unclear. Stretch-activated and voltage-gated calcium ion channels have been shown to be involved in the mechanoregulation of chondrocytes in vitro. In this study, we analyse, for the first time, how blocking these ion channels influences the effects of mechanical loading on chick joint morphogenesis. Using in vitro culture of embryonic chick hindlimb explants in a mechanostimulation bioreactor, we block stretch-activated and voltage-gated ion channels using, respectively, gadolinium chloride and nifedipine. We find that the administration of high doses of either drug largely removed the effects of mechanical stimulation on growth and shape development in vitro, while neither drug had any effect in static cultures. This study demonstrates that, during joint morphogenesis, mechanical cues are transduced—at least in part—through mechanosensitive calcium ion channels, advancing our understanding of cartilage development and mechanotransduction.
Date Issued
2018-11-05
Date Acceptance
2018-08-02
Citation
Philosophical Transactions B: Biological Sciences, 2018, 373 (1759)
ISSN
0962-8436
Publisher
Royal Society, The
Journal / Book Title
Philosophical Transactions B: Biological Sciences
Volume
373
Issue
1759
Copyright Statement
© 2018 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution
License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original
author and source are credited.
License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original
author and source are credited.
Sponsor
Commission of the European Communities
Grant Number
336306
Subjects
Science & Technology
Life Sciences & Biomedicine
Biology
Life Sciences & Biomedicine - Other Topics
joint development
developmental biomechanics
mechanotransduction
calcium ion channels
bioreactor
CALCIUM-CHANNELS
ARTICULAR CHONDROCYTES
SKELETAL MORPHOGENESIS
INTRACELLULAR CALCIUM
DYNAMIC COMPRESSION
CONTRAST AGENT
GROWTH-PLATE
GADOLINIUM
TRANSDUCTION
MOVEMENT
06 Biological Sciences
11 Medical And Health Sciences
Evolutionary Biology
Publication Status
Published
Article Number
20170317
Date Publish Online
2018-09-24