Bone Tissue Collagen Maturity and Mineral Content Increase With Sustained Hyperglycemia in the KK-Ay Murine Model of Type 2 Diabetes

J Bone Miner Res. 2018 May;33(5):921-929. doi: 10.1002/jbmr.3365. Epub 2018 Feb 8.

Abstract

Type 2 diabetes mellitus (T2DM) increases fracture risk for a given bone mineral density (BMD), which suggests that T2DM changes bone tissue properties independently of bone mass. In this study, we assessed the effects of hyperglycemia on bone tissue compositional properties, enzymatic collagen crosslinks, and advanced glycation end-products (AGEs) in the KK-Ay murine model of T2DM using Fourier transform infrared (FTIR) imaging and high-performance liquid chromatography (HPLC). Compared to KK-aa littermate controls (n = 8), proximal femoral bone tissue of KK-Ay mice (n = 14) exhibited increased collagen maturity, increased mineral content, and less heterogeneous mineral properties. AGE accumulation assessed by the concentration of pentosidine, as well as the concentrations of the nonenzymatic crosslinks hydroxylysylpyridinoline (HP) and lysyl pyridinoline (LP), did not differ in the proximal femurs of KK-Ay mice compared to controls. The observed differences in tissue-level compositional properties in the KK-Ay mice are consistent with bone that is older and echo observations of reduced remodeling in T2DM. © 2017 American Society for Bone and Mineral Research.

Keywords: COLLAGEN: BONE MATRIX; GENETIC ANIMAL MODELS: ANIMAL MODELS; MATRIX MINERALIZATION: BONE MATRIX; OTHER: ANALYSIS/QUANTITATION OF BONE; OTHER: DISEASES AND DISORDERS OF/RELATED TO BONE.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bone Density*
  • Collagen / metabolism*
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology
  • Glycation End Products, Advanced / metabolism*
  • Hyperglycemia / metabolism*
  • Hyperglycemia / pathology
  • Male
  • Mice

Substances

  • Glycation End Products, Advanced
  • Collagen