Prenatal muscle forces are necessary for vertebral segmentation and disc structure, but not for notochord involution in mice
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Embryonic muscle forces are necessary for normal vertebral development and spinal curvature, but their involvement in intervertebral disc (IVD) development remains unclear. The aim of the current study was to determine how muscle contractions affect (1) notochord involution and vertebral segmentation, and (2) IVD development including the mechanical properties and morphology, as well as collagen fibre alignment in the annulus fibrosus. Muscular dysgenesis (mdg) mice were harvested at three prenatal stages: at Theiler Stage (TS)22 when notochord involution starts, at TS24 when involution is complete, and at TS27 when the IVD is formed. Vertebral and IVD development were characterised using histology, immunofluorescence, and indentation testing. Our results revealed that notochord involution and vertebral segmentation occurred independently of muscle contractions between TS22 and TS24. However, in the absence of muscle contractions, we found vertebral fusion in the cervical region at TS27, along with (i) a displacement of the nucleus pulposus towards the dorsal side, (ii) a disruption of the structural arrangement of collagen in the annulus fibrosus, and (iii) an increase in viscous behaviour of the annulus fibrosus. These findings emphasise the important role of mechanical forces during IVD development, and demonstrate a critical role of muscle loading during development to enable proper annulus fibrosus formation. Our findings further suggest a need for mechanical loading in the creation of fibre-reinforced tissue engineering replacement IVDs as a therapy for IVD degeneration.
Date Issued
2021-07-01
Date Acceptance
2021-02-28
Citation
European Cells and Materials, 2021, 41, pp.558-575
ISSN
1473-2262
Publisher
European Cells & Materials Ltd
Start Page
558
End Page
575
Journal / Book Title
European Cells and Materials
Volume
41
Copyright Statement
© 2021 The Author(s). This article is distributed in accordance with Creative Commons Attribution Licence
(http://creativecommons.org/licenses/by-sa/4.0/).
(http://creativecommons.org/licenses/by-sa/4.0/).
License URL
Sponsor
Commission of the European Communities
The Leverhulme Trust
Identifier
https://www.ecmjournal.org/papers/vol041/pdf/v041a36.pdf
Grant Number
336306
RPG-2014-339
Subjects
Science & Technology
Life Sciences & Biomedicine
Technology
Cell & Tissue Engineering
Engineering, Biomedical
Materials Science, Biomaterials
Orthopedics
Cell Biology
Engineering
Materials Science
Intervertebral disc
development
spine
biomechanics
notochord
muscular dysgenesis
embryo
paralysis
ECM
collagens
INDENTATION LOAD-RELAXATION
INTERVERTEBRAL DISC
EXTRACELLULAR-MATRIX
ANNULUS FIBROSUS
SPINAL CURVATURE
MOUSE
PAX3
DEGENERATION
STIMULI
GROWTH
Biomedical Engineering
0601 Biochemistry and Cell Biology
0903 Biomedical Engineering
Publication Status
Published
Date Publish Online
2021-07-01