TY - JOUR
T1 - Advanced glycation endproducts and bone material properties in type 1 diabetic mice
AU - Rubin, Mishaela R.
AU - Paschalis, Eleftherios P.
AU - Poundarik, Atharva
AU - Sroga, Gyna E.
AU - McMahon, Donald J.
AU - Gamsjaeger, Sonja
AU - Klaushofer, Klaus
AU - Vashishth, Deepak
N1 - Publisher Copyright:
© 2016 Rubin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Fractures, particularly at the lower extremities and hip, are a complication of diabetes. In both type 1 (T1D) and type 2 diabetes (T2D), fracture risk is disproportionately worse than that predicted from the measurement of bone mineral density. Although an explanation for this discrepancy is the presence of organic matrix abnormalities, it has not been fully elucidated how advanced glycation endproducts (AGEs) relate to bone deterioration at both the macroscopic and microscopic levels. We hypothesized that there would be a relationship between skeletal AGE levels (determined by Raman microspectroscopy at specific anatomical locations) and bone macroscopic and microscopic properties, as demonstrated by the biomechanical measures of crack growth and microindentation respectively. We found that in OVE26 mice, a transgenic model of severe early onset T1D, AGEs were increased by Raman (carboxymethyl-lysine [CML] wildtype (WT): 0.0143±0.0005 vs T1D: 0.0175 ±0.0002, p = 0.003) at the periosteal surface. These differences were associated with less tough bone in T1D by fracture mechanics (propagation toughness WT: 4.73±0.32 vs T1D: 3.39±0.24 NM/m1/2, p = 0.010) and by reference point indentation (indentation distance increase WT: 6.85±0.44 vs T1D: 9.04±0.77 μm; p = 0.043). Within T1D, higher AGEs by Raman correlated inversely with macroscopic bone toughness. These data add to the existing body of knowledge regarding AGEs and the relationship between skeletal AGEs with biomechanical indices.
AB - Fractures, particularly at the lower extremities and hip, are a complication of diabetes. In both type 1 (T1D) and type 2 diabetes (T2D), fracture risk is disproportionately worse than that predicted from the measurement of bone mineral density. Although an explanation for this discrepancy is the presence of organic matrix abnormalities, it has not been fully elucidated how advanced glycation endproducts (AGEs) relate to bone deterioration at both the macroscopic and microscopic levels. We hypothesized that there would be a relationship between skeletal AGE levels (determined by Raman microspectroscopy at specific anatomical locations) and bone macroscopic and microscopic properties, as demonstrated by the biomechanical measures of crack growth and microindentation respectively. We found that in OVE26 mice, a transgenic model of severe early onset T1D, AGEs were increased by Raman (carboxymethyl-lysine [CML] wildtype (WT): 0.0143±0.0005 vs T1D: 0.0175 ±0.0002, p = 0.003) at the periosteal surface. These differences were associated with less tough bone in T1D by fracture mechanics (propagation toughness WT: 4.73±0.32 vs T1D: 3.39±0.24 NM/m1/2, p = 0.010) and by reference point indentation (indentation distance increase WT: 6.85±0.44 vs T1D: 9.04±0.77 μm; p = 0.043). Within T1D, higher AGEs by Raman correlated inversely with macroscopic bone toughness. These data add to the existing body of knowledge regarding AGEs and the relationship between skeletal AGEs with biomechanical indices.
UR - https://www.scopus.com/pages/publications/84969522896
U2 - 10.1371/journal.pone.0154700
DO - 10.1371/journal.pone.0154700
M3 - Article
C2 - 27140650
AN - SCOPUS:84969522896
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 5
M1 - e0154700
ER -