Lack of embryonic skeletal muscle in mice leads to abnormal mineral deposition and growth
Artikel i vetenskaplig tidskrift, 2025

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.

X-ray fluorescence

Zinc

Synchrotron imaging

Hydroxyapatite

Mechanobiology

X-ray scattering

Författare

Isabella Silva Barreto

Institutionen för Biomedicinsk Teknik

Marianne Liebi

Chalmers, Fysik, Materialfysik

Ecole Polytechnique Federale de Lausanne (EPFL)

Paul Scherrer Institut

Sophie Le Cann

Institutionen för Biomedicinsk Teknik

Laboratoire Modélisation et Simulation Multi Echelle (MSME)

Saima Ahmed

Imperial College London

Leonard Nielsen

Chalmers, Fysik, E-commons

Tilman A. Grünewald

European Synchrotron Radiation Facility (ESRF)

Hector Dejea

Max IV-laboratoriet

Institutionen för Biomedicinsk Teknik

Viviane Lutz-Bueno

Paul Scherrer Institut

Niamh C. Nowlan

University College Dublin

Imperial College London

Hanna Isaksson

Institutionen för Biomedicinsk Teknik

Journal of Structural Biology

1047-8477 (ISSN) 1095-8657 (eISSN)

Vol. 217 1 108178

Multi-Modal Tensor Tomography (MUMOTT)

Europeiska kommissionen (EU) (EC/H2020/949301), 2021-01-01 -- 2025-12-31.

Ämneskategorier (SSIF 2025)

Klinisk medicin

DOI

10.1016/j.jsb.2025.108178

PubMed

39956301

Mer information

Senast uppdaterat

2025-03-11