Correlation Between the Nano-Structure and the Macro-Mechanics of the Human Intervertebral Discs

Author(s):  
Darwesh M. K. Aladin ◽  
Kenneth M. C. Cheung ◽  
Alfonso H. W. Ngan ◽  
Danny Chan ◽  
Victor Y. L. Leung ◽  
...  

The intervertebral disc (IVD) consists of three major components: the gelatinous nucleus pulposus (NP) at the centre, surrounded by concentric layers of annulus fibrosus (AF), and the superior and inferior endplates sandwiching the AF and NP intact. Collagen fibrils are the main structural components in all three parts of the disc. The dry mass of collagen in the IVD is about 70% [1]. The outer AF is predominantly collagen I with minor traces of collagen II. A gradual replacement in the collagen I by collagen II occurs in the inner regions [2]. Lumbar disc degenerative disease or early-onset disc degeneration is a primary cause for sciatica and low back pain in young individuals. The most significant biochemical change that occurs in disc degeneration is the loss of proteoglycans in the nucleus pulposus [3]. The mechanical inability of collagen fibrils to withstand the load may be one of the factors causing the loss of proteoglycans. The reason why collagen degrades may be environmental or genetic [4,5]. Researchers are working on developing tissue engineered disc replacements, stem cell therapy etc. to treat disc degeneration. Understanding the disc environment at the nano level is essential in order for these techniques to be clinically successful, as it is well known that the environment in the extracellular matrix plays an important role in determining the stem cells’ fate [6]. Therefore, in order to gain a better understanding on the role played by these matrix proteins, this study aimed at evaluating the correlation between the nano scale properties of the disc collagens with the disc tissue’s macro mechanics.

Author(s):  
Darwesh M. K. Aladin ◽  
Kenneth M. C. Cheung ◽  
Alfonso H. W. Ngan ◽  
Danny Chan ◽  
Victor Y. L. Leung ◽  
...  

The intervertebral disc (IVD) consists of three major components: the gelatinous nucleus pulposus (NP) at the centre, surrounded by concentric layers of annulus fibrosus (AF), and the superior and inferior endplates sandwiching the AF and NP. Collagen fibrils are the main structural components in all three parts of the disc. The dry mass of collagen in the IVD is about 70% [1]. The outer AF is predominantly collagen I with minor traces of collagen II. A gradual replacement in the collagen I by collagen II occurs in the inner regions [2]. Lumbar disc degenerative disease or early-onset disc degeneration is a primary cause for sciatica and low back pain in young individuals. The most significant biochemical change that occurs in disc degeneration is the loss of proteoglycans in the nucleus pulposus [3]. The mechanical inability of collagen fibrils to withstand the load may be one of the factors causing the loss of proteoglycans. The reason why collagen degrades may be environmental or genetic [4,5]. Researchers are working on developing tissue engineered disc replacements, stem cell therapy etc. to treat disc degeneration. Understanding the disc environment at the nano level is essential in order for these techniques to be clinically successful, as it is well known that the environment in the extracellular matrix plays an important role in determining the stem cells’ fate [6]. Therefore, in order to gain a better understanding on the role played by these matrix proteins, this study aimed at evaluating the correlation between the nano scale properties of the disc collagens with the disc tissue’s macro mechanics.


2012 ◽  
Vol 2 (1) ◽  
pp. 6 ◽  
Author(s):  
Marie Klauser ◽  
Franck Forterre ◽  
Marcus Doherr ◽  
Andreas Zurbriggen ◽  
David Spreng ◽  
...  

Disc degeneration occurs commonly in dogs. A variety of factors is thought to contribute an inappropriate disc matrix that isolate cells in the disc and lead to apoptosis. Disc herniation with radiculopathy and discogenic pain are the results of the degenerative process. The objective of this prospective study was to determine the extent of apoptosis in intact and herniated intervertebral discs of chondrodystrophic dogs and non-chondrodystrophic dogs. In addition, the nucleus pulposus (NP) was histologically compared between non-chondrodystrophic and chondrodystrophic dogs. Thoracolumbar intervertebral discs and parts of the extruded nucleus pulposus were harvested from 45 dogs. Samples were subsequently stained with haematoxylin-eosin and processed to detect cleaved caspase-3 and poly(ADP-ribose) polymerase. A significant greater degree of apoptosis was observed in herniated NPs of chondrodystrophic dogs compared to non- chondrodystrophic dogs with poly (ADP-ribose) polymerase and cleaved caspase- 3 detection. Within the group of chondrodystrophic dogs, dogs with an intact disc and younger than 6 years showed a significant lower incidence of apoptosis in the NP compared to the herniated NP of chondrodystrophic dogs. The extent of apoptosis in the annulus fibrosus was not different between the intact disc from chondrodystrophic and non- chondrodystrophic dogs. An age-related increase of apoptotic cells in NP and annulus fibrosus was found in the intact non-herniated intervertebral discs. Histologically, absence of notochordal cells and occurrence of chondroid metaplasia were observed in the nucleus pulposus of chondrodystrophic dogs. As a result, we found that apoptosis plays a role in disc degeneration in chondrodystrophic dogs.


Author(s):  
John I. Boxberger ◽  
Joshua D. Auerbach ◽  
Sounok Sen ◽  
George R. Dodge ◽  
Dawn M. Elliott

Reduced nucleus pulposus glycosaminoglycan (GAG) content is one of the earliest clinically detectable changes during the course of intervertebral disc degeneration [1,2]. Depletion of nucleus GAG by small percentages consistent with this early loss has been experimentally linked to altered motion segment mechanical function, and thus, potentially increases the risk of damage accumulation directly due to elevated stresses and strains and through altered cellular function [3]. Recently, our laboratory has established an in vivo model in a rat lumbar disc which moderately decreases nucleus GAG to levels observed in early human degeneration. In this model, GAG loss is accompanied by a state of hypermobility at both 4 and 12 weeks post treatment [4], potentially making the disc susceptible to mechanical failure. The objective of this study was to determine the long term effects of nucleus GAG depletion and to determine if altered discs demonstrate hallmark features of disc degeneration. We hypothesized that GAG will remain depleted 24 weeks post treatment, potentially decreasing to lower levels, and further that geometrical and mechanical changes consistent with degeneration will be observed.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Zhaohui Zhai ◽  
Zhaoxin Li ◽  
Zhonglei Ji ◽  
Xiaosheng Lu

Objective. Polygonatum sibiricum polysaccharide (PSP) has antioxidant activity, immune enhancement, and other biological properties. However, the effect of PSP on intervertebral disc degeneration has not been reported. In this study, we mainly investigated the effect of PSP on the apoptosis, inflammation, and oxidative stress of nucleus pulposus cells (NPCs) during the process of intervertebral disc degeneration. Methods. A rat NPC model induced by H2O2 was constructed. The CCK8 method was used to measure the effects of PSP on the apoptosis of rat NPCs induced by H2O2. The effects on the activity of SOD and content of MDA were also determined. The rat model of intervertebral disc degeneration was treated with PSP for 1 month, and the mRNA expression levels of IL-1β, COX2, iNOS, Col2α1, Col10α1, and MMP3 were measured by qPCR in the tissue of intervertebral disc. NPCs from the degenerated intervertebral discs were separated, and the cell viability was measured by the CCK8 method. The contents of SOD and MDA in NPCs were determined as well. Results. PSP significantly reduced the apoptosis of NPCs induced by H2O2, significantly increased the SOD content, and decreased the content of MDA in H2O2-induced NPCs. The expression level of IL-1β, COX2, and iNOS in the rat model with intervertebral disc degeneration was significantly downregulated after 1 month of PSP treatment. PSP treatment increased the expression of Col2α1 type and significantly decreased the expression of Col10α1 type collagen and MMP3 in rats with disc degeneration. PSP treatment significantly reduced NPC apoptosis and increased its SOD content and reduced MDA content, which is consistent with the results from cell-level experiments. Conclusion. PSP can effectively reduce the apoptosis, inflammation, and oxidative stress of H2O2-induced NPCs in rats with intervertebral disc degeneration and mitigate the progression of intervertebral disc degeneration, which has the potential to be developed as new drugs for the treatment of intervertebral disc degeneration.


Climacteric ◽  
2014 ◽  
Vol 17 (6) ◽  
pp. 700-704 ◽  
Author(s):  
C. Lou ◽  
H-L. Chen ◽  
X-Z. Feng ◽  
G-H. Xiang ◽  
S-P. Zhu ◽  
...  

2021 ◽  
pp. 219256822110123
Author(s):  
Yongming Jin ◽  
Guangfeng Mao ◽  
Chen Yang ◽  
Chen Xia ◽  
Chuyong Chen ◽  
...  

Study Design: A prospective study. Objectives: Intervertebral disc degenerative disease is a common and frequently-occurring disease in adults and is the main cause of lower back pain. However, there is a lack of universal animal models to study disc degeneration. Methods: Forty-two male New Zealand white rabbits aged 12 months were used in this study. We established an endplate ischemic disc degeneration model though surgical ligation of rabbit lumbar vertebral body segment arteries. Two weeks after surgery, 6 experimental animals were randomly selected for follow-up tests. First, ischemia and lumbar disc degeneration were confirmed using imaging techniques. Then, immunohistochemical staining was performed to observe the growth of the annulus fibrosus. Finally, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting were used to detect mRNA expression and protein content of IL-1α, TNFα, collagen II, MMP-3, aggrecan, and PLA2 in the nucleus pulposus of the disc. Results: Imaging examination confirmed the successful construction of a lumbar disc degeneration model. Histological analysis and biochemical analysis showed a damaged intervertebral disc structure, and collagen II and aggrecan, the key extracellular matrix components of intervertebral discs, were reduced in synthesis and content. The synthesis and expression of IL-1α, TNFα, PLA2, and MMP-3 related to disc catabolism and inflammatory response were enhanced. Conclusions: We successfully constructed a lumbar disc degeneration ischemia model, which provides a novel approach to study the pathological mechanisms involved in discogenic low back pain and to prevent and treat discogenic low back pain.


Author(s):  
Hassan M. Raheem ◽  
Skip E. Rochefort ◽  
Brian K. Bay

AbstractWe have developed a simple, inexpensive and innovative device for reproducing the global mechanical behavior of spinal motion segments and the local mechanical environment experienced by lumbar intervertebral discs. The device has several broad functions: (1) exploration of the basic mechanics underlying this complex skeletal system, (2) connecting changes in tissue characteristics with overall motion segment function, and (3) evaluation of strategies for repair and replacement of disc components. This “disc emulator” consists of three main parts: (1) an artificial annulus fibrosus (AAF), made out of silicone, with lumbar disc geometry and adjustable material properties, (2) a hydrogel nucleus pulposus (NP) also with lumbar disc geometry and adjustable material properties, and (3) simulated vertebral bodies 3D printed with trabecular bone simulated by a rigid polymer (Acrylonitrile Butadiene Styrene, ABS) and end plates crafted from a compliant polymer (Thermoplastic Polyurethane, TPU). Mechanical compression experiments have been conducted using the disc emulator under similar protocols to published studies of human cadaver samples. Bulging of the artificial annulus fibrosus was examined under axial compression loads using digital image correlation (DIC), and results show close agreement. We see this approach of using anatomical geometry and multiple adjustable components as a useful means of creating accurate local stress/strain environments for preliminary material evaluation, without the variability and difficulty inherent indirect testing of cadaveric materials.


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