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Lack of embryonic skeletal muscle in mice leads to abnormal mineral deposition and growth

Silva Barreto, Isabella LU orcid ; Liebi, Marianne ; Le Cann, Sophie LU ; Ahmed, Saima ; Nielsen, Leonard ; Grünewald, Tilman A. ; Dejea, Hector LU ; Lutz-Bueno, Viviane ; Nowlan, Niamh C. and Isaksson, Hanna LU orcid (2025) In Journal of Structural Biology 217(1).
Abstract
Developing bones can be severely impaired by a range of disorders where muscular loading is abnormal. Recent work has indicated that the effects of absent skeletal muscle on bones are more severe early in development, with rudiment length and mineralization lengths being almost normal in muscle-less limbs just prior to birth. However, the impact of abnormal mechanical loading on the nanoscale structure and composition during prenatal mineralization remains unknown. In this exploratory study, we characterized the mineralization process of humeri from muscle-less limb embryonic mice using a multiscale approach by combining X-ray scattering and fluorescence with infrared and light microscopy to identify potential key aspects of interest for... (More)
Developing bones can be severely impaired by a range of disorders where muscular loading is abnormal. Recent work has indicated that the effects of absent skeletal muscle on bones are more severe early in development, with rudiment length and mineralization lengths being almost normal in muscle-less limbs just prior to birth. However, the impact of abnormal mechanical loading on the nanoscale structure and composition during prenatal mineralization remains unknown. In this exploratory study, we characterized the mineralization process of humeri from muscle-less limb embryonic mice using a multiscale approach by combining X-ray scattering and fluorescence with infrared and light microscopy to identify potential key aspects of interest for future in-depth investigations. Muscle-less humeri were characterized by initially less mineralized tissue to later catch up with controls, and exhibited continuous growth of mineral particles, which ultimately led to seemingly larger mineral particles than their controls at the end of development. Muscle-less limbs exhibited an abnormal pattern of mineralization, reflected by a more widespread distribution of zinc and homogenous distribution of hydroxyapatite compared to controls, which instead showed trabecular-like structures and zinc localized only to regions of ongoing mineralization. The decrease in collagen content in the hypertrophic zone due to resorption of the cartilage collagen matrix was less distinct in muscle-less limbs compared to controls. Surprisingly, the nanoscale orientation of the mineral particles was unaffected by the lack of skeletal muscle. The identified accelerated progression of ossification in muscle-less limbs at later prenatal stages provides a possible anatomical mechanism underlying their recovery in skeletal development. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Structural Biology
volume
217
issue
1
article number
108178
publisher
Elsevier
external identifiers
  • scopus:85218937592
  • pmid:39956301
ISSN
1095-8657
DOI
10.1016/j.jsb.2025.108178
language
English
LU publication?
yes
id
6aaf567a-f4e3-4d96-a0d0-3a21985363c3
date added to LUP
2025-03-12 13:17:17
date last changed
2025-04-04 13:58:07
@article{6aaf567a-f4e3-4d96-a0d0-3a21985363c3,
  abstract     = {{Developing bones can be severely impaired by a range of disorders where muscular loading is abnormal. Recent work has indicated that the effects of absent skeletal muscle on bones are more severe early in development, with rudiment length and mineralization lengths being almost normal in muscle-less limbs just prior to birth. However, the impact of abnormal mechanical loading on the nanoscale structure and composition during prenatal mineralization remains unknown. In this exploratory study, we characterized the mineralization process of humeri from muscle-less limb embryonic mice using a multiscale approach by combining X-ray scattering and fluorescence with infrared and light microscopy to identify potential key aspects of interest for future in-depth investigations. Muscle-less humeri were characterized by initially less mineralized tissue to later catch up with controls, and exhibited continuous growth of mineral particles, which ultimately led to seemingly larger mineral particles than their controls at the end of development. Muscle-less limbs exhibited an abnormal pattern of mineralization, reflected by a more widespread distribution of zinc and homogenous distribution of hydroxyapatite compared to controls, which instead showed trabecular-like structures and zinc localized only to regions of ongoing mineralization. The decrease in collagen content in the hypertrophic zone due to resorption of the cartilage collagen matrix was less distinct in muscle-less limbs compared to controls. Surprisingly, the nanoscale orientation of the mineral particles was unaffected by the lack of skeletal muscle. The identified accelerated progression of ossification in muscle-less limbs at later prenatal stages provides a possible anatomical mechanism underlying their recovery in skeletal development.}},
  author       = {{Silva Barreto, Isabella and Liebi, Marianne and Le Cann, Sophie and Ahmed, Saima and Nielsen, Leonard and Grünewald, Tilman A. and Dejea, Hector and Lutz-Bueno, Viviane and Nowlan, Niamh C. and Isaksson, Hanna}},
  issn         = {{1095-8657}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Structural Biology}},
  title        = {{Lack of embryonic skeletal muscle in mice leads to abnormal mineral deposition and growth}},
  url          = {{http://dx.doi.org/10.1016/j.jsb.2025.108178}},
  doi          = {{10.1016/j.jsb.2025.108178}},
  volume       = {{217}},
  year         = {{2025}},
}