Effects of abnormal muscle forces on prenatal joint morphogenesis in mice
File(s)Sotiriou_et_al_final_JOR_2019_with_figs.docx (7.31 MB)
Accepted version
Author(s)
Sotiriou, Vivien
Rolfe, Rebecca A
Murphy, Paula
Nowlan, Niamh C
Type
Journal Article
Abstract
Fetal movements are essential for normal development of the human skeleton. When fetal movements are reduced or restricted, infants are at higher risk of developmental dysplasia of the hip and arthrogryposis (multiple joint contractures). Joint shape abnormalities have been reported in mouse models with abnormal or absent musculature, but the effects on joint shape in such models have not been quantified or characterised in detail. In this study, embryonic mouse forelimbs and hindlimbs at a single developmental stage (Theiler Stage 23) with normal, reduced or absent muscle were imaged in 3D. Skeletal rudiments were virtually segmented and rigid image registration was used to reliably align rudiments with each other, enabling repeatable assessment and measurement of joint shape differences between normal, reduced-muscle and absent muscle groups. We demonstrate qualitatively and quantitatively that joint shapes are differentially affected by a lack of, or reduction in, skeletal muscle, with the elbow joint being the most affected of the major limb joints. Surprisingly, the effects of reduced muscle were often more pronounced than those of absent skeletal muscle, indicating a complex relationship between muscle mass and joint morphogenesis. These findings have relevance for human developmental disorders of the skeleton in which abnormal fetal movements are implicated, particularly developmental dysplasia of the hip and arthrogryposis.
Date Issued
2019-11
Date Acceptance
2019-07-02
Citation
Journal of Orthopaedic Research, 2019, 37 (11), pp.2287-2296
ISSN
0736-0266
Publisher
Wiley
Start Page
2287
End Page
2296
Journal / Book Title
Journal of Orthopaedic Research
Volume
37
Issue
11
Copyright Statement
© 2019 Owner. This is the accepted version of the following article: Sotiriou, V. , Rolfe, R. A., Murphy, P. and Nowlan, N. C. (2019), Effects of abnormal muscle forces on prenatal joint morphogenesis in mice. J. Orthop. Res. Accepted Author Manuscript. doi:10.1002/jor.24415, which has been published in final form at https://doi.org/10.1002/jor.24415
Sponsor
Commission of the European Communities
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31297860
Grant Number
336306
Subjects
Fetal movements
biomechanics
image registration
joint development
joint shape
mouse embryos
muscleless limbs
reduced muscle
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2019-08-12