Effects of Collagen Post-Translational Modifications on Bone Density and Mechanical Properties in Osteogenesis Imperfecta

Master thesis (2018)

Authors

S.O. Smit Mechanical Engineering

Contributors

Harrie Weinans (mentor)
B. Pouran (mentor)
Wouter Nijhuis (mentor)
A.A. Zadpoor (graduation committee member)
D. Dodou (graduation committee member)
Faculty
Mechanical Engineering, Mechanical Engineering
Copyright: © 2018 Stefan Smit
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Published Date

09-12-2018

Language

English

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Faculty

Mechanical Engineering

Abstract

Osteogenesis imperfecta (OI), also known as brittle bone disease, affects 1 in 10.000 births. This disease is characterized by skeletal dysplasias, bone fragility and many secondary health issues. It is a heritable disorder affecting collagen type I, which is an essential protein in bone tissue. Post-translational overmodifications in collagen biosynthesis disturb the collagen packing and alter the mineralization process. This results in bone with poor structural parameters and inferior mechanical properties. In the current study, we have tested the hypothesis that the structural and mechanical properties in bone samples from OI patients are related to altered post-translational modifications in the collagen molecules.Hydroxylysine (Hyl) and the crosslinks hydroxylysyl-pyridinoline (HP) and lysyl-pyridinoline (LP) in bone samples from OI patients were measured with liquid chromatography. Bone quantity, in terms of volumetric bone mineral density (vBMD) and volumetric tissue mineral density (vTMD), was measured with micro-computed tomography. Hardness and Young’s moduli were derived from indentation experiments. Lysine was overhydroxylated in OI bone (p < 0.001), which led to increased HP values (p < 0.001) and higher HP/LP ratios (p = 0.013) compared to controls. OI tissue mineral density was more heterogeneously distributed, although average vTMD values were similar in both groups. The vBMD was significantly higher in controls compared to OI bone samples. Elevated Hyl levels were significantly related to decreased vBMD and vTMD in bone samples from OI patients. In both OI and control samples, an increase in LP crosslinks was associated with elevated vTMD values. Indentation with a spherical tip (r = 0.25mm) showed no altered mechanical properties in OI compared with controls. Unfortunately, we could not determine if impaired overmodifications in collagen are related to the poor mechanical properties of OI bone. Young’s moduli and hardness were not related to HP levels or HP/LP ratios. In control bone samples a negative correlation between Hyl residues and mechanical properties is observed. More mechanical experiments are necessary to address the hypothesis appropriately.