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Effects of abnormal muscle forces on prenatal joint morphogenesis in mice

Vivien Sotiriou, Rebecca A Rolfe, Paula Murphy, Niamh C Nowlan
doi: https://doi.org/10.1101/669267
Vivien Sotiriou
Department of Bioengineering, Imperial College London, UK
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Rebecca A Rolfe
Department of Bioengineering, Imperial College London, UKDepartment of Zoology, School of Natural Sciences, Trinity College Dublin, The University of Dublin, Ireland
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Paula Murphy
Department of Zoology, School of Natural Sciences, Trinity College Dublin, The University of Dublin, Ireland
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Niamh C Nowlan
Department of Bioengineering, Imperial College London, UK
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  • For correspondence: n.nowlan@imperial.ac.uk
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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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted June 13, 2019.
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Effects of abnormal muscle forces on prenatal joint morphogenesis in mice
Vivien Sotiriou, Rebecca A Rolfe, Paula Murphy, Niamh C Nowlan
bioRxiv 669267; doi: https://doi.org/10.1101/669267
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Effects of abnormal muscle forces on prenatal joint morphogenesis in mice
Vivien Sotiriou, Rebecca A Rolfe, Paula Murphy, Niamh C Nowlan
bioRxiv 669267; doi: https://doi.org/10.1101/669267

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