Dietary Advanced Glycation End-Product Consumption Leads to Mechanical Stiffening of Murine Intervertebral Discs

Abstract

ABSTRACTBack pain is a leading cause of disability strongly associated with intervertebral disc (IVD) degeneration. Reducing structural disruption and catabolism in IVD degeneration remains an important clinical challenge. Pro-oxidant and structure-modifying advanced glycation end-products (AGEs) contribute to obesity and diabetes, which are associated with increased back pain, and accumulate in tissues due to hyperglycemia or ingestion of foods processed at high heat. Collagen-rich IVDs are particularly susceptible to AGE accumulation due to their slow metabolic rates yet it is unclear if dietary AGEs can cross the endplates to accumulate in IVDs. We apply a dietary mouse model to test the hypothesis that chronic consumption of high AGE diets results in sex-specific IVD structural disruption and functional changes. High AGE diet resulted in AGE accumulation in IVDs and increased IVD compressive stiffness, torque range, and failure torque, particularly for females. These biomechanical changes were likely caused by significantly increased AGE crosslinking in the annulus fibrosus, measured by multiphoton imaging. Increased collagen damage measured with collagen hybridizing peptide may be a risk factor for IVD degeneration as these animals age. The greater influence of high AGE diet on females is an important area of future investigation that may involve AGE receptors, known to interact with estrogen. We conclude high AGE diets can be a source for IVD crosslinking and collagen damage known to be important in IVD degeneration. This suggests dietary and other interventions that modify AGEs warrant further investigation and may be particularly important for diabetics where AGEs accumulate more rapidly.Summary StatementDietary advanced glycation end-products (AGE) lead to sex-specific intervertebral disc structural and functional changes and may be targeted for promoting spinal health especially in diabetes where AGEs form rapidly.