Noninvasive cumulative axial load may induce intervertebral disc degeneration-A potential rabbit model

Abstract

Intervertebral disc degeneration (IDD) is considered to be the main cause of many spinal disorders; however, its underlying pathophysiology is not clearly understood. Recent studies indicate that excessive mechanical loading may serve a major role in the initiation of IDD. The aim of the present study was to explore the effect of noninvasive cumulative axial loading on the intervertebral discs of the lumbar spine using a novel rabbit model. Rabbits in the experimental group were placed into individual tubes specifically designed to force maintenance of an upright posture and were loaded with a heavy collar to increase the intradiscal pressure of their lumbar spine. Radiograph imaging and magnetic resonance imaging (MRI) was performed every 4 weeks to provide evidence of disc degeneration. At the end of the experiment, the animals were sacrificed and disc specimens were harvested for quantitative polymerase chain reaction and histological analysis. MRI results revealed significant and progressive reductions in the signal intensities of lumbar discs in the experimental group compared with the control group throughout the 14-week study period. The expression level of type I collagen was significantly increased and the expression levels of type II collagen and aggrecan were significantly decreased in the experimental group compared with the control group (P<0.05). Histological examination revealed marked structural changes in the experimental group, including fibrocartilage-like tissue ingrowth and accelerated fibrotic changes of the nucleus pulposus. The results of the present study indicate that noninvasive cumulative axial load is able to induce accelerated degenerative changes in rabbit lumbar discs, which may provide useful information for the establishment of a novel animal model of IDD for the research of IDD in humans.

p300 arrests intervertebral disc degeneration by regulating the FOXO3/Sirt1/Wnt/β‐catenin axis

“…IDD, a leading contributor to various chronic and debilitating disorders of the spine, and its pathophysiology remains unclarified (Bai et al, 2017). In this study, we attempted to investigate in what measure p300, FOXO3, and Sirt1 might affect the development of IDD via regulation of the Wnt/β‐catenin pathway; our results showed that p300‐mediated FOXO3 increases in Sirt1 inhibited the Wnt/β‐catenin pathway, which promotes autophagy and inhibits apoptosis of NPCs.…”

Pharmacological Effects of Resveratrol in Intervertebral Disc Degeneration: A Literature Review

“…Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases with thrombo‐spondin motif proteins (ADAMTSs) are the main force of ECM remolding during IDD 64,65 . At the cellular level, mechanical load, oxidative stress, high glucose and inflammatory response can induce ECM catabolism 65–68 . Han et al 69 .…”

“…64,65 At the cellular level, mechanical load, oxidative stress, high glucose and inflammatory response can induce ECM catabolism. [65][66][67][68] Han et al 69 investigated the effects of RSV on ECM under mechanical compression. The results showed high-magnitude mechanical compression seriously decreased ECM content, while treatment with RSV could increase the proteoglycan content, biochemical content (glycosaminoglycan (GAG) and hydroxyproline (HYP)) and anabolic factors (Sox-9, aggrecan and collagen II) of ECM.…”

“… 64 , 65 At the cellular level, mechanical load, oxidative stress, high glucose and inflammatory response can induce ECM catabolism. 65 , 66 , 67 , 68 Han et al . 69 investigated the effects of RSV on ECM under mechanical compression.…”

Biomaterials for intervertebral disc regeneration: Current status and looming challenges

“…Rats (Walsh & Lotz, 2004) Upright posture with axial load in lumbar spine Rabbits (Bai, Wang, Zhou, et al, 2017) Genetic modification Smad3 gene knockout Mice (Li, Liang, Zhou, et al, 2009)…”