Glycation of Human Cortical and Cancellous Bone Captures Differences in the Formation of Maillard Reaction Products between Glucose and Ribose

Sroga, Grażyna E.; Siddula, Alankrita; Vashishth, Deepak

doi:10.1371/journal.pone.0117240

Cited by 39 publications

(52 citation statements)

References 62 publications

(79 reference statements)

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“…First, the formation of AGEs and crosslinks induced by ribose treatment was not directly quantified, however previous investigations have provided direct molecular evidence for pentosidine formation in tissue incubated with ribose [47,48]. Additionally, in this work the indirect measurements of AGE formation by fluorescence showed clear changes after ribose treatment, comparable to the previous reports [47][48][49].…”

Section: Discussionsupporting

confidence: 79%

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue

et al. 2017

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Concurrent with a progressive loss of regenerative capacity, connective tissue aging is characterized by a progressive accumulation of Advanced Glycation End-products (AGEs). Besides being part of the typical aging process, type II diabetics are particularly affected by AGE accumulation due to abnormally high levels of systemic glucose that increases the glycation rate of long-lived proteins such as collagen. Although AGEs are associated with a wide range of clinical disorders, the mechanisms by which AGEs contribute to connective tissue disease in aging and diabetes are still poorly understood. The present study harnesses advanced multiscale imaging techniques to characterize a widely employed in vitro model of ribose induced collagen aging and further benchmarks these data against experiments on native human tissues from donors of different age. These efforts yield unprecedented insight into the mechanical changes in collagen tissues across hierarchical scales from molecular, to fiber, to tissue-levels. We observed a linear increase in molecular spacing (from 1.45 nm to 1.5 nm) and a decrease in the D-period length (from 67.5 nm to 67.1 nm) in aged tissues, both using the ribose model of in vitro glycation and in native human probes. Multiscale mechanical analysis of in vitro glycated tendons strongly suggests that AGEs reduce tissue viscoelasticity by severely limiting fiber-fiber and fibril-fibril sliding. This study lays an important foundation for interpreting the functional and biological effects of AGEs in collagen connective tissues, by exploiting experimental models of AGEs crosslinking and benchmarking them for the first time against endogenous AGEs in native tissue.

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Section: Discussionsupporting

confidence: 79%

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue

et al. 2017

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“…The findings presented here are also different from another report that the AGE pentosidine did not correlate with bone mechanical properties . The previous study measured pentosidine, which composes a small percentage of fAGEs in cortical bone (<5%), and was conducted in bovine bone. In contrast, our study provides more comprehensive information regarding AGEs as fAGEs were measured rather than a single AGE.…”

Section: Discussioncontrasting

confidence: 99%

“…The AGE content in specimens from the previous study were also 10‐fold less than AGEs within our study . This drastic difference in AGEs may be attributed to the use of glucose incubation in the prior study, as in vitro incubation using glucose compared with ribose results in the formation of fewer AGEs …”

Section: Discussionmentioning

confidence: 37%

In Vitro‐Induced High Sugar Environments Deteriorate Human Cortical Bone Elastic Modulus and Fracture Toughness

Merlo

Aaronson

Vaidya

et al. 2019

Journal Orthopaedic Research

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Advanced glycation end-products (AGEs) have been suggested to contribute to bone fragility in type 2 diabetes (T2D). AGEs can be induced through in vitro sugar incubations but there is limited data on the effect of total fluorescent AGEs on mechanical properties of human cortical bone, which may have altered characteristics in T2D. Thus, to examine the effect of AGEs on bone directly in T2D patients with uncontrolled sugar levels, it is essential to first understand the fundamental mechanisms by studying the effects of controlled in vitro-induced AGEs on cortical bone mechanical behavior. Here, human cortical bone specimens from female cadaveric tibias (ages 57-87) were incubated in an in vitro 0.6 M ribose or vehicle solution (n = 20/group) for 10 days at 37°C, their mechanical properties were assessed by microindentation and fracture toughness tests, and induced AGE levels were quantified through a fluorometric assay. Results indicated that ribose-incubated bone had significantly more AGEs (+81%, p ≤ 0.005), lower elastic modulus assessed by traditional microindentation, and lower fracture toughness compared with vehicle controls. Furthermore, based on pooled data, increased AGEs were significantly correlated with deteriorated mechanical properties. The findings presented here show that the accumulation of AGEs allows for lower stiffness and increased ability to initiate a crack in human cortical bone. Statement of clinical significance: High sugar levels as in T2D results in deteriorated bone quality via AGE accumulation with a consequent weakening in bone's mechanical integrity.

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“…Each supernatant was transferred to a clean tube and used directly for the assays or stored at −80°C as needed. Determination of pentosidine was performed using ultra-high pressure liquid chromatography (UPLC) [23,24]. …”

Section: Methodsmentioning

confidence: 99%

“…Currently, non-enzymatic cross-links are measured using high-performance liquid chromatography (HPLC) [22–24] or fluorometric assays [7,21]. While these methods provide direct quantitative information on the amount of non-enzymatic cross-links, they do have certain limitations.…”

Section: Introductionmentioning

confidence: 99%

Assessment of collagen quality associated with non-enzymatic cross-links in human bone using Fourier-transform infrared imaging

Schmidt¹,

Zimmermann²,

Campbell

et al. 2017

Bone

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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 crosslinks, 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.

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Glycation of Human Cortical and Cancellous Bone Captures Differences in the Formation of Maillard Reaction Products between Glucose and Ribose

Cited by 39 publications

References 62 publications

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue

In Vitro‐Induced High Sugar Environments Deteriorate Human Cortical Bone Elastic Modulus and Fracture Toughness

Assessment of collagen quality associated with non-enzymatic cross-links in human bone using Fourier-transform infrared imaging

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