Chronic Ingestion of Advanced Glycation End Products Induces Degenerative Spinal Changes and Hypertrophy in Aging Pre-Diabetic Mice

• Type of Material: Article
• Authors: Svenja Illien-Junger, Emory University; Young Lu, Icahn School of Medicine at Mount Sinai; Sheeraz A. Qureshi, Icahn School of Medicine at Mount Sinai; Andrew C. Hecht, Icahn School of Medicine at Mount Sinai; Weijing Cai, Icahn School of Medicine at Mount Sinai; Helen Vlassara, Icahn School of Medicine at Mount Sinai; Gary E. Striker, Icahn School of Medicine at Mount Sinai; James C. Iatridis, Icahn School of Medicine at Mount Sinai
• Language: English
• Date: 2015-02-10
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Illien-Jünger et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0116625
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 10
• Issue: 2
• Start Page: e0116625
• End Page: e0116625
• Grant/Funding Information: Funding provided by JCI: National Institute of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS; R01AR051146) http://www.niams.nih.gov/.; HV: National Institute of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK; RO1 AG023188) http://www.niddk.nih.gov/.; GES: Juvenile Diabetes Research Foundation (JDRF; 17-2008-1041) https://jdrf.org/.
• Keywords: Science & Technology; CANCELLOUS BONE; TYPE-2 DIABETES-MELLITUS; INSULIN-RESISTANCE; Multidisciplinary Sciences; Science & Technology - Other Topics; BACK-PAIN; BODY-MASS INDEX; NONENZYMATIC GLYCATION; DIETARY GLYCOTOXINS; RISK-FACTOR; OXIDANT STRESS; INTERVERTEBRAL DISC DEGENERATION
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Anatomy

Abstract

Intervertebral disc (IVD) degeneration and pathological spinal changes are major causes of back pain, which is the top cause of global disability. Obese and diabetic individuals are at increased risk for back pain and musculoskeletal complications. Modern diets contain high levels of advanced glycation end products (AGEs), cyto-toxic components which are known contributors to obesity, diabetes and accelerated aging pathologies. There is little information about potential effects of AGE rich diet on spinal pathology, which may be a contributing cause for back pain which is common in obese and diabetic individuals. This study investigated the role of specific AGE precursors (e.g. methylglyoxal-derivatives (MG)) on IVD and vertebral pathologies in aging C57BL6 mice that were fed isocaloric diets with standard (dMG+) or reduced amounts of MG derivatives (dMG-; containing 60-70% less dMG). dMG+ mice exhibited a pre-diabetic phenotype, as they were insulin resistant but not hyperglycemic. Vertebrae of dMG+ mice displayed increased cortical-thickness and cortical-area, greater MG-AGE accumulation and ectopic calcification in vertebral endplates. IVD morphology of dMG+ mice exhibited ectopic calcification, hypertrophic differentiation and glycosaminoglycan loss relative to dMG- mice. Overall, chronic exposure to dietary AGEs promoted age-accelerated IVD degeneration and vertebral alterations involving ectopic calcification which occurred in parallel with insulin resistance, and which were prevented with dMG- diet. This study described a new mouse model for diet-induced spinal degeneration, and results were in support of the hypothesis that chronic AGE ingestion could be a factor contributing to a pre-diabetic state, ectopic calcifications in spinal tissues, and musculoskeletal complications that are more generally known to occur with chronic diabetic conditions.