TY - JOUR
T1 - Assessment of collagen quality associated with non-enzymatic cross-links in human bone using Fourier-transform infrared imaging
AU - Schmidt, F. N.
AU - Zimmermann, E. A.
AU - Campbell, G. M.
AU - Sroga, G. E.
AU - Püschel, K.
AU - Amling, M.
AU - Tang, S. Y.
AU - Vashishth, D.
AU - Busse, B.
N1 - Funding Information:
This project was supported by the German Research Foundation (DFG) under grant no. BU 2562/2-1/3-1 and the Partnership for Innovation, Education and Research (PIER) under grant no. PIF-2015-43. Felix Schmidt acknowledges the Joachim Herz Stiftung for a PhD Scholarship in cooperation with the PIER Helmholtz Graduate School, University of Hamburg and DESY Hamburg. Dr. Zimmermann is supported through a postdoctoral fellowship from the Alexander von Humboldt Foundation. Dr. Vashishth acknowledges the support of NIH grant AG20618.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - Aging and many disease conditions, most notably diabetes, are associated with the accumulation of non-enzymatic cross-links in the bone matrix. The non-enzymatic cross-links, also known as advanced glycation end products (AGEs), occur at the collagen tissue level, where they are associated with reduced plasticity and increased fracture risk. In this study, Fourier-transform infrared (FTIR) imaging was used to detect spectroscopic changes associated with the formation of non-enzymatic cross-links in human bone collagen. Here, the non-enzymatic cross-link profile was investigated in one cohort with an in vitro ribose treatment as well as another cohort with an in vivo bisphosphonate treatment. With FTIR imaging, the two-dimensional (2D) spatial distribution of collagen quality associated with non-enzymatic cross-links was measured through the area ratio of the 1678/1692 cm − 1 subbands within the amide I peak, termed the non-enzymatic crosslink-ratio (NE-xLR). The NE-xLR increased by 35% in the ribation treatment group in comparison to controls (p < 0.005), with interstitial bone tissue being more susceptible to the formation of non-enzymatic cross-links. Ultra high-performance liquid chromatography, fluorescence microscopy, and fluorometric assay confirm a correlation between the non-enzymatic cross-link content and the NE-xLR ratio in the control and ribated groups. High resolution FTIR imaging of the 2D bone microstructure revealed enhanced accumulation of non-enzymatic cross-links in bone regions with higher tissue age (i.e., interstitial bone). This non-enzymatic cross-link ratio (NE-xLR) enables researchers to study not only the overall content of AGEs in the bone but also its spatial distribution, which varies with skeletal aging and diabetes mellitus and provides an additional measure of bone's propensity to fracture.
AB - Aging and many disease conditions, most notably diabetes, are associated with the accumulation of non-enzymatic cross-links in the bone matrix. The non-enzymatic cross-links, also known as advanced glycation end products (AGEs), occur at the collagen tissue level, where they are associated with reduced plasticity and increased fracture risk. In this study, Fourier-transform infrared (FTIR) imaging was used to detect spectroscopic changes associated with the formation of non-enzymatic cross-links in human bone collagen. Here, the non-enzymatic cross-link profile was investigated in one cohort with an in vitro ribose treatment as well as another cohort with an in vivo bisphosphonate treatment. With FTIR imaging, the two-dimensional (2D) spatial distribution of collagen quality associated with non-enzymatic cross-links was measured through the area ratio of the 1678/1692 cm − 1 subbands within the amide I peak, termed the non-enzymatic crosslink-ratio (NE-xLR). The NE-xLR increased by 35% in the ribation treatment group in comparison to controls (p < 0.005), with interstitial bone tissue being more susceptible to the formation of non-enzymatic cross-links. Ultra high-performance liquid chromatography, fluorescence microscopy, and fluorometric assay confirm a correlation between the non-enzymatic cross-link content and the NE-xLR ratio in the control and ribated groups. High resolution FTIR imaging of the 2D bone microstructure revealed enhanced accumulation of non-enzymatic cross-links in bone regions with higher tissue age (i.e., interstitial bone). This non-enzymatic cross-link ratio (NE-xLR) enables researchers to study not only the overall content of AGEs in the bone but also its spatial distribution, which varies with skeletal aging and diabetes mellitus and provides an additional measure of bone's propensity to fracture.
KW - Advanced glycation end products
KW - Bisphosphonates
KW - Bone quality
KW - Collagen
KW - Fourier transform infrared spectroscopy
KW - Non-enzymatic cross-links
UR - http://www.scopus.com/inward/record.url?scp=85011587074&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2017.01.015
DO - 10.1016/j.bone.2017.01.015
M3 - Article
C2 - 28109917
AN - SCOPUS:85011587074
VL - 97
SP - 243
EP - 251
JO - Bone
JF - Bone
SN - 8756-3282
ER -