title: Chronic ingestion of advanced glycation end products induces degenerative spinal changes and hypertrophy in aging pre-diabetic mice.
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.
authors: Leni & Peter W. May Department of Orthopaedics/Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors: Svenja
authors: S
authors: Illien-Jünger
authors: Leni & Peter W. May Department of Orthopaedics/Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors: Young
authors: Y
authors: Lu
authors: Leni & Peter W. May Department of Orthopaedics/Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors: Sheeraz A
authors: SA
authors: Qureshi
authors: Leni & Peter W. May Department of Orthopaedics/Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors: Andrew C
authors: AC
authors: Hecht
authors: Department of Geriatrics and Palliative Care, Division of Experimental Diabetes and Aging/Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors: Weijing
authors: W
authors: Cai
authors: Department of Geriatrics and Palliative Care, Division of Experimental Diabetes and Aging/Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors: Helen
authors: H
authors: Vlassara
authors: Department of Geriatrics and Palliative Care, Division of Experimental Diabetes and Aging, and Division of Nephrology, Department of Medicine/Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors: Gary E
authors: GE
authors: Striker
authors: Leni & Peter W. May Department of Orthopaedics/Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
authors: James C
authors: JC
authors: Iatridis
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D004032:Diet / Q000009:adverse effects*; D017127:Glycation End Products, Advanced / Q000009:adverse effects*; D006652:Histological Techniques; D007150:Immunohistochemistry; D007333:Insulin Resistance; D055959:Intervertebral Disc Degeneration / Q000139:chemically induced* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011765:Pyruvaldehyde / Q000633:toxicity
chemical_list: D017127:Glycation End Products, Advanced; D011765:Pyruvaldehyde