English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Alterations of bone material properties in growing Ifitm5/BRIL p.S42 knock-in mice, a new model for atypical type VI osteogenesis imperfecta

Hedjazi, G., Guterman-Ram, G., Blouin, S., Schemenz, V., Wagermaier, W., Fratzl, P., et al. (2022). Alterations of bone material properties in growing Ifitm5/BRIL p.S42 knock-in mice, a new model for atypical type VI osteogenesis imperfecta. Bone, 162: 116451. doi:10.1016/j.bone.2022.116451.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files

Locators

show
hide
Locator:
Article (Publisher version)
Description:
-

Creators

show
hide
 Creators:
Hedjazi, Ghazal, Author
Guterman-Ram, Gali, Author
Blouin, Stéphane, Author
Schemenz, Victoria1, Author              
Wagermaier, Wolfgang1, Author              
Fratzl, Peter2, Author              
Hartmann, Markus A., Author
Zwerina, Jochen, Author
Fratzl-Zelman, Nadja, Author
Marini, Joan C., Author
Affiliations:
1Wolfgang Wagermaier, Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863296              
2Peter Fratzl, Biomaterialien, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863294              

Content

show
hide
Free keywords: Osteogenesis imperfecta; Growing mice; Bone matrix mineralization; Osteocyte lacunae; Osteocyte canalicular network; Bone vascularity; Collagen orientation
 Abstract: Introduction Osteogenesis imperfecta (OI) is a heterogenous group of heritable connective tissue disorders characterized by high bone fragility due to low bone mass and impaired bone material properties. Atypical type VI OI is an extremely rare and severe form of bone dysplasia resulting from a loss-of-function mutation (p.S40L) in IFITM5/BRIL, the causative gene of OI type V and decreased osteoblast secretion of pigment epithelium-derived factor (PEDF), as in OI type VI. It is not yet known which alterations at the material level might lead to such a severe phenotype. We therefore characterized bone tissue at the micrometer level in a novel heterozygous Ifitm5/BRIL p.S42L knock-in murine model at 4 and 8 weeks of age. Methods We evaluated in female mice, total body size, femoral and lumbar bone mineral density (BMD) by dual-energy X-ray absorptiometry. In the femoral bone we examined osteoid deposition by light microscopy, assessed bone histomorphometry and mineralization density distribution by quantitative backscattered electron imaging (qBEI). Osteocyte lacunae were examined by qBEI and the osteocyte lacuno-canalicular network by confocal laser scanning microscopy Vasculature was examined indirectly by qBEI as 2D porosity in cortex, and as 3D porosity by micro-CT in third trochanter. Collagen orientation was examined by second harmonic generation microscopy. Two-way ANOVA was used to discriminate the effect of age and genotype. Results Ifitm5/BRIL p.S42L female mice are viable, do not differ in body size, fat and lean mass from wild type (WT) littermates but have lower whole-body, lumbar and femoral BMD and multiple fractures. The average and most frequent calcium concentration, CaMean and CaPeak, increased with age in metaphyseal and cortical bone in both genotypes and were always higher in Ifitm5/BRIL p.S42L than in WT, except CaMean in metaphysis at 4 weeks of age. The fraction of highly mineralized bone area, CaHigh, was also increased in Ifitm5/BRIL p.S42L metaphyseal bone at 8 weeks of age and at both ages in cortical bone. The fraction of lowly mineralized bone area, CaLow, decreased with age and was not higher in Ifitm5/BRIL p.S42L, consistent with lack of hyperosteoidosis on histological sections by visual exam. Osteocyte lacunae density was higher in Ifitm5/BRIL p.S42L than WT, whereas canalicular density was decreased. Indirect measurements of vascularity revealed a higher pore density at 4 weeks in cortical bone of Ifitm5/BRIL p.S42L than in WT and at both ages in the third trochanter. Importantly, the proportion of bone area with disordered collagen fibrils was highly increased in Ifitm5/BRIL p.S42L at both ages. Conclusions Despite normal skeletal growth and the lack of a collagen gene mutation, the Ifitm5/BRIL p.S42L mouse shows major OI-related bone tissue alterations such as hypermineralization of the matrix and elevated osteocyte porosity. Together with the disordered lacuno-canalicular network and the disordered collagen fibril orientation, these abnormalities likely contribute to overall bone fragility.

Details

show
hide
Language(s): eng - English
 Dates: 2022-05-302022
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.bone.2022.116451
PMID: 0630
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Bone
  Other : Bone
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: New York : Elsevier
Pages: - Volume / Issue: 162 Sequence Number: 116451 Start / End Page: - Identifier: ISSN: 8756-3282