Prenatal murine skeletogenesis partially recovers from absent skeletal muscle as development progresses
File(s)v044a08.pdf (4.97 MB)
Published version
Author(s)
Sotiriou, Vivien
Huang, Yuming
Ahmed, Saima
Nowlan, Niamh
Type
Journal Article
Abstract
Skeletal muscle contractions are critical for normal skeletal growth and morphogenesis but it is unclear how the detrimental effects of absent muscle on the bones and joints change over time. Joint shape and cavitation as well as rudiment length and mineralisation were assessed in multiple rudiments at two developmental stages [Theiler stage (TS)24 and TS27] in the splotch-delayed “muscle-less limb” mouse model and littermate controls. Chondrocyte morphology was quantified in 3D in the distal humerus at the same stages. As development progressed, the effects of absent muscle on all parameters except for cavitation become less severe. All major joints in muscle-less limbs were abnormally shaped at TS24, while, by TS27, most muscle-less limb joint shapes were normal or nearly normal. In contrast, any joints that were fused at TS24 did not cavitate by TS27. At TS24, chondrocytes in the distal humerus were significantly smaller in the muscle-less limbs than in controls, while by TS27, chondrocyte volume was similar between the two groups, offering a cell-level mechanism for the partial recovery in shape of muscle-less limbs. Mineralisation showed the most pronounced changes over gestation. At TS24, all muscle-less rudiments studied had less mineralisation than the controls, while at TS27, muscle-less limb rudiments had mineralisation extents equivalent to controls. In conclusion, the effects of muscle absence on prenatal murine skeletogenesis reduced in severity over gestation. Understanding how mammalian bones and joints continue to develop in an environment with abnormal fetal movements provides insights into conditions including hip dysplasia and arthrogryposis.
Date Issued
2022-11-08
Date Acceptance
2022-10-10
Citation
European Cells and Materials, 2022, 44, pp.115-132
ISSN
1473-2262
Publisher
European Cells & Materials Ltd
Start Page
115
End Page
132
Journal / Book Title
European Cells and Materials
Volume
44
Copyright Statement
© 2022 The Author(s). This article is distributed in accordance with Creative Commons Attribution Licence
(http://creativecommons.org/licenses/by/4.0/).
(http://creativecommons.org/licenses/by/4.0/).
License URL
Sponsor
Commission of the European Communities
Grant Number
336306
Subjects
Muscle, Skeletal
Humerus
Joints
Animals
Mammals
Mice
Morphogenesis
Pregnancy
Muscle Contraction
Female
Biomedical Engineering
0601 Biochemistry and Cell Biology
0903 Biomedical Engineering
Publication Status
Published