Multiscale, Converging Defects of Macro-Porosity, Microstructure and Matrix Mineralization Impact Long Bone Fragility in NF1

Kühnisch, Jirko; Seto, Jong; Kolanczyk, Mateusz

Multiscale, Converging Defects of Macro-Porosity, Microstructure and Matrix Mineralization Impact Long Bone Fragility in NF1

Dateien

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Datum

2014

Autor:innen

Kühnisch, Jirko

Seto, Jong

Kolanczyk, Mateusz

Publikationstyp

Zeitschriftenartikel

unikn.publication.listelement.citation.prefix.version.undefined

PLoS ONE. 2014, 9(1), e86115. eISSN 1932-6203. Available under: doi: 10.1371/journal.pone.0086115

Zusammenfassung

Bone fragility due to osteopenia, osteoporosis or debilitating focal skeletal dysplasias is a frequent observation in the Mendelian disease Neurofibromatosis type 1 (NF1). To determine the mechanisms underlying bone fragility in NF1 we analyzed two conditional mouse models, Nf1Prx1 (limb knock-out) and Nf1Col1 (osteoblast specific knock-out), as well as cortical bone samples from individuals with NF1. We examined mouse bone tissue with micro-computed tomography, qualitative and quantitative histology, mechanical tensile analysis, small-angle X-ray scattering (SAXS), energy dispersive X-ray spectroscopy (EDX), and scanning acoustic microscopy (SAM). In cortical bone of Nf1Prx1 mice we detected ectopic blood vessels that were associated with diaphyseal mineralization defects. Defective mineral binding in the proximity of blood vessels was most likely due to impaired bone collagen formation, as these areas were completely devoid of acidic matrix proteins and contained thin collagen fibers. Additionally, we found significantly reduced mechanical strength of the bone material, which was partially caused by increased osteocyte volume. Consistent with these observations, bone samples from individuals with NF1 and tibial dysplasia showed increased osteocyte lacuna volume. Reduced mechanical properties were associated with diminished matrix stiffness, as determined by SAM. In line with these observations, bone tissue from individuals with NF1 and tibial dysplasia showed heterogeneous mineralization and reduced collagen fiber thickness and packaging. Collectively, the data indicate that bone fragility in NF1 tibial dysplasia is partly due to an increased osteocyte-related micro-porosity, hypomineralization, a generalized defect of organic matrix formation, exacerbated in the regions of tensional and bending force integration, and finally persistence of ectopic blood vessels associated with localized macro-porotic bone lesions.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

KÜHNISCH, Jirko, Jong SETO, Mateusz KOLANCZYK, 2014. Multiscale, Converging Defects of Macro-Porosity, Microstructure and Matrix Mineralization Impact Long Bone Fragility in NF1. In: PLoS ONE. 2014, 9(1), e86115. eISSN 1932-6203. Available under: doi: 10.1371/journal.pone.0086115

BibTex

@article{Kuhnisch2014Multi-30633,
  year={2014},
  doi={10.1371/journal.pone.0086115},
  title={Multiscale, Converging Defects of Macro-Porosity, Microstructure and Matrix Mineralization Impact Long Bone Fragility in NF1},
  number={1},
  volume={9},
  journal={PLoS ONE},
  author={Kühnisch, Jirko and Seto, Jong and Kolanczyk, Mateusz},
  note={Article Number: e86115}
}

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