Abstract
Type 2 diabetes mellitus (T2DM) is associated with advanced glycation end product (AGE) enrichment and considered a risk factor for intervertebral disc (IVD) degeneration. We hypothesized that systemic AGE inhibition, achieved using pyridoxamine (PM), attenuates IVD degeneration in T2DM rats. To induce IVD degeneration, lumbar disc injury or sham surgery was performed on Zucker Diabetic Sprague Dawley (ZDSD) or control Sprague Dawley (SD) rats. Post-surgery, IVD-injured ZDSD rats received daily PM dissolved in drinking water or water only. The resulting groups were SD uninjured, SD injured, ZDSD uninjured, ZDSD injured, and ZDSD injured + PM. Levels of blood glycation and disc degeneration were investigated. At week 8 post-surgery, glycated serum protein (GSP) levels were increased in ZDSDs compared to SDs. PM treatment attenuated this increase. Micro-MRI analysis demonstrated IVD dehydration in injured versus uninjured SDs and ZDSDs. In the ZDSD injured + PM group, IVD dehydration was diminished compared to ZDSD injured. AGE levels were decreased and aggrecan levels increased in ZDSD injured + PM versus ZDSD injured rats. Histological and immunohistochemical analyses further supported the beneficial effect of PM. In summary, PM attenuated GSP levels and IVD degeneration processes in ZDSD rats, demonstrating its potential to attenuate IVD degeneration in addition to managing glycemia in T2DM.
Highlights
Low back pain (LBP) is a leading cause of global disability [1]
T2-weighted μMRI image analysis demonstrated a reduction in nucleus pulposus (NP) hydration in the Sprague Dawley (SD) injured and Zucker Diabetic Sprague-Dawley (ZDSD) injured groups at 8 post-surgery compared to the same groups pre-surgery
Using a type 2 diabetes mellitus—intervertebral disc (IVD) degeneration rat model, this study demonstrates the potential of oral PM treatment to reduce levels of glycated serum protein (GSP) and to attenuate advanced glycation end product (AGE) levels and NP destruction in injured IVDs in diabetes
Summary
Previous research demonstrates an association between intervertebral disc (IVD) degeneration and LBP that increases as the number of affected intervertebral disc levels increases [2]. IVD degeneration is a multifactorial disease that includes alterations in function and the increased death of nucleus pulposus (NP) cells, upregulated levels of proinflammatory cytokines and associated catabolic enzymes in the disc microenvironment, and changes in biomechanical properties [3,4]. In this study we used a rat model, since it is large enough for surgical alteration of the spinal structures and allows defined biobehavioral testing for analyzing discogenic pain [11]. In a prior study by our group, an 18-gauge (G) needle-induced IVD injury in rats led to consistent severe disc degeneration and was associated with discogenic pain [12]
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