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Sample records for disc degeneration model

  1. [Research advances in animal models of intervertebral disc degeneration].

    PubMed

    Zhang, Wenli; Liu, Hao; Li, Tanzhu

    2007-11-01

    To review the research advances in animal models of human disc degeneration. The relative articles in recent years were extensively reviewed. Studies both at home and abroad were analyzed and classified. The advantages and disadvantages of each method were compared. Studies were classified as either experimentally induced models or spontaneous models. The induced models were subdivided as mechanical (alteration of forces on the normal disc), structural (injury or chemical alteration) and genetically induced models. Spontaneous models included those animals that naturally developed degenerative disc disease. Animal model of intervertebral disc degeneration is an important path for revealing the pathogenesis of human disc degeneration, and play an important role in testing novel interventions. With recent advances in the relevance of animal models and humans, it has a great prospect in study of human disc degeneration.

  2. Modeling and optimization of an elastic arthroplastic disc for a degenerated disc

    NASA Astrophysics Data System (ADS)

    Ghouchani, Azadeh; Ravari, Mohammad; Mahmoudi, Farid

    2011-10-01

    A three-dimensional finite element model (FEM) of the L3-L4 motion segment using ABAQUS v 6.9 has been developed. The model took into account the material nonlinearities and is imposed different loading conditions. In this study, we validated the model by comparison of its predictions with several sets of experimental data. Disc deformation under compression and segmental rotational motions under moment loads for the normal disc model agreed well with the corresponding in vivo studies. By linking ABAQUS with MATLAB 2010.a, we determined the optimal Young s modulus as well as the Poisson's ratio for the artificial disc under different physiologic loading conditions. The results of the present study confirmed that a well-designed elastic arthroplastic disc preferably has an annulus modulus of 19.1 MPa and 1.24 MPa for nucleus section and Poisson ratio of 0.41 and 0.47 respectively. Elastic artificial disc with such properties can then achieve the goal of restoring the disc height and mechanical function of intact disc under different loading conditions and so can reduce low back pain which is mostly caused due to disc degeneration.

  3. A Review of Animal Models of Intervertebral Disc Degeneration: Pathophysiology, Regeneration, and Translation to the Clinic

    PubMed Central

    Ghosh, Peter

    2016-01-01

    Lower back pain is the leading cause of disability worldwide. Discogenic pain secondary to intervertebral disc degeneration is a significant cause of low back pain. Disc degeneration is a complex multifactorial process. Animal models are essential to furthering understanding of the degenerative process and testing potential therapies. The adult human lumbar intervertebral disc is characterized by the loss of notochordal cells, relatively large size, essentially avascular nature, and exposure to biomechanical stresses influenced by bipedalism. Animal models are compared with regard to the above characteristics. Numerous methods of inducing disc degeneration are reported. Broadly these can be considered under the categories of spontaneous degeneration, mechanical and structural models. The purpose of such animal models is to further our understanding and, ultimately, improve treatment of disc degeneration. The role of animal models of disc degeneration in translational research leading to clinical trials of novel cellular therapies is explored. PMID:27314030

  4. Experimental model of intervertebral disc degeneration by needle puncture in Wistar rats

    PubMed Central

    Issy, A.C.; Castania, V.; Castania, M.; Salmon, C.E.G.; Nogueira-Barbosa, M.H.; Bel, E. Del; Defino, H.L.A.

    2013-01-01

    Animal models of intervertebral disc degeneration play an important role in clarifying the physiopathological mechanisms and testing novel therapeutic strategies. The objective of the present study is to describe a simple animal model of disc degeneration involving Wistar rats to be used for research studies. Disc degeneration was confirmed and classified by radiography, magnetic resonance and histological evaluation. Adult male Wistar rats were anesthetized and submitted to percutaneous disc puncture with a 20-gauge needle on levels 6-7 and 8-9 of the coccygeal vertebrae. The needle was inserted into the discs guided by fluoroscopy and its tip was positioned crossing the nucleus pulposus up to the contralateral annulus fibrosus, rotated 360° twice, and held for 30 s. To grade the severity of intervertebral disc degeneration, we measured the intervertebral disc height from radiographic images 7 and 30 days after the injury, and the signal intensity T2-weighted magnetic resonance imaging. Histological analysis was performed with hematoxylin-eosin and collagen fiber orientation using picrosirius red staining and polarized light microscopy. Imaging and histological score analyses revealed significant disc degeneration both 7 and 30 days after the lesion, without deaths or systemic complications. Interobserver histological evaluation showed significant agreement. There was a significant positive correlation between histological score and intervertebral disc height 7 and 30 days after the lesion. We conclude that the tail disc puncture method using Wistar rats is a simple, cost-effective and reproducible model for inducing disc degeneration. PMID:23532265

  5. Experimental model of intervertebral disc degeneration by needle puncture in Wistar rats.

    PubMed

    Issy, A C; Castania, V; Castania, M; Salmon, C E G; Nogueira-Barbosa, M H; Bel, E Del; Defino, H L A

    2013-03-01

    Animal models of intervertebral disc degeneration play an important role in clarifying the physiopathological mechanisms and testing novel therapeutic strategies. The objective of the present study is to describe a simple animal model of disc degeneration involving Wistar rats to be used for research studies. Disc degeneration was confirmed and classified by radiography, magnetic resonance and histological evaluation. Adult male Wistar rats were anesthetized and submitted to percutaneous disc puncture with a 20-gauge needle on levels 6-7 and 8-9 of the coccygeal vertebrae. The needle was inserted into the discs guided by fluoroscopy and its tip was positioned crossing the nucleus pulposus up to the contralateral annulus fibrosus, rotated 360° twice, and held for 30 s. To grade the severity of intervertebral disc degeneration, we measured the intervertebral disc height from radiographic images 7 and 30 days after the injury, and the signal intensity T2-weighted magnetic resonance imaging. Histological analysis was performed with hematoxylin-eosin and collagen fiber orientation using picrosirius red staining and polarized light microscopy. Imaging and histological score analyses revealed significant disc degeneration both 7 and 30 days after the lesion, without deaths or systemic complications. Interobserver histological evaluation showed significant agreement. There was a significant positive correlation between histological score and intervertebral disc height 7 and 30 days after the lesion. We conclude that the tail disc puncture method using Wistar rats is a simple, cost-effective and reproducible model for inducing disc degeneration.

  6. Effects of controlled dynamic disc distraction on degenerated intervertebral discs: an in vivo study on the rabbit lumbar spine model.

    PubMed

    Kroeber, Markus; Unglaub, Frank; Guehring, Thorsten; Guegring, Thorsten; Nerlich, Andreas; Hadi, Tamer; Lotz, Jeffrey; Carstens, Claus

    2005-01-15

    An in vivo study on the rabbit lumbar spine model. Effects of temporary dynamic distraction on intervertebral discs were studied on the lumbar spine rabbit model to characterize the changes associated with disc distraction and to evaluate feasibility of temporary disc distraction to previously compressed discs in order to stimulate disc regeneration. Studies have shown that accelerated degeneration of the intervertebral disc results from altered mechanical loading conditions. The development of methods for the prevention of disc degeneration and the restoration of disc tissue that has already degenerated are needed. New Zealand white rabbits (n = 32) were used for this study. The rabbits were randomly assigned to one of five groups. In 12 animals, the discs were first loaded for 28 days using a custom-made external loading device to stimulate disc degeneration. After 28 days loading time, the discs in six animals were distracted for 7 days and in six animals for 28 days using the same external device, however, modified as dynamic distraction device. In six animals, the discs were distracted for 28 days without previous loading; and in six animals, the discs were loaded for 28 days and afterwards the loading device removed for 28 days for recovery without distraction. Six animals were sham operated. The external device was situated; however, the discs remained undistracted and they also served as controls. After 28 to 56 days loading and distraction time, the animals were killed and the lumbar spine was harvested for examination. Disc height, disc morphology, cell viability, relative neutral zone, and tangent modulus were measured. After 28 days of loading, the discs demonstrated a significant decrease in disc space. Histologically, disorganization of the architecture of the anulus occurred. The number of dead cells increased significantly in the anulus and cartilage endplate. These changes were reversible after 28 days of distraction. The disc thickness increased

  7. Histological Features of the Degenerating Intervertebral Disc in a Goat Disc-injury Model

    PubMed Central

    Zhang, Yejia; Drapeau, Susan; An, Howard S.; Markova, Dessislava; Lenart, Brett A.; Anderson, D. Greg

    2010-01-01

    Study Design An in vivo study to develop a goat large-animal model for intervertebral disc (IVD) degeneration. Objectives To determine an optimal method for inducing goat IVD degeneration suitable for testing disc regeneration therapies. Summary of Background Data Although rodent, rabbit, and other small animal studies are useful, the narrow dimensions of IVDs in these species limit studies requiring injection of a relevant volume of therapeutics or implantation of engineered tissue constructs. For this study, the goat was selected because the size and shape of their IVDs are comparable to those of adult humans. Methods A minimally invasive approach that did not cause significant morbidity or mortality to adult goats (n = 6) was used. Under fluoroscopic guidance, goat lumbar IVDs were injured with a 4.5 mm drill bit or #15 or #10 surgical blades. Two months post-injury, the goats were euthanized and their IVDs with adjacent endplates were isolated, decalcified and stained. Results A numerical histological scale to categorize the degree of goat IVD degeneration was developed based on the histological features of rabbit IVDs previously described by Masuda et al., goat IVDs described by Hoogendoorn et al., and human IVDs described by Boos et al. The inter-rater agreement of our scoring system was assessed (weighted Kappa value = 0.6646). Mann-Whitney tests were used to compare the injured IVDs with uninjured control. A 4.5 mm drill bit inserted to a 15 mm depth resulted in a significantly higher histological score compared to uninjured controls (p = 0.01). Injury with a #15 or #10 blade did not result in increased histological scores compared with uninjured controls. Conclusions A comparison of the various injuries inflicted showed that the use of a 4.5 mm drill bit resulted in the most significant histological changes. PMID:21245789

  8. Biomechanics of Disc Degeneration

    PubMed Central

    Palepu, V.; Kodigudla, M.; Goel, V. K.

    2012-01-01

    Disc degeneration and associated disorders are among the most debated topics in the orthopedic literature over the past few decades. These may be attributed to interrelated mechanical, biochemical, and environmental factors. The treatment options vary from conservative approaches to surgery, depending on the severity of degeneration and response to conservative therapies. Spinal fusion is considered to be the “gold standard” in surgical methods till date. However, the association of adjacent level degeneration has led to the evolution of motion preservation technologies like spinal arthroplasty and posterior dynamic stabilization systems. These new technologies are aimed to address pain and preserve motion while maintaining a proper load sharing among various spinal elements. This paper provides an elaborative biomechanical review of the technologies aimed to address the disc degeneration and reiterates the point that biomechanical efficacy followed by long-term clinical success will allow these nonfusion technologies as alternatives to fusion, at least in certain patient population. PMID:22745914

  9. Transplantation of goat bone marrow stromal cells to the degenerating intervertebral disc in a goat disc-injury model

    PubMed Central

    Zhang, Yejia; Drapeau, Susan; An, Howard S.; Thonar, Eugene J-M.A.; Anderson, D. Greg

    2010-01-01

    Study Design In vivo randomized controlled study in the goat intervertebral disc (IVD) injury model. Objective To define the effects of allogeneic bone marrow-derived stromal cell injected into the degenerating goat IVDs. Summary of Background Data Transplantation of bone marrow stromal cells to the degenerating disc has been suggested as a means to correct the biologic incompetence of the disc. However, large animal models with IVDs similar in shape and size to those of humans are needed to define the efficacy and safety of this approach. Methods Goat IVD degeneration was induced by stabbing with a #15 blade. One month after disc injury, the injured discs were randomly selected to receive goat bone marrow-derived stromal cell (suspended in hydrogel), saline (control), or hydrogel (control) injections. Three and 6 months after stem cell transplantation, goats were euthanized and the IVD were examined for biochemical content and tissue morphology. MR images at 3- and 6-month time points were also examined. Results The goat large animal model shows early degenerative changes following disc injury. Degenerating IVDs injected with bone marrow stromal cells showed significantly increased proteoglycan (PG) accumulation within their nucleus pulposus (NP) region. However, collagen content, MRI grade and histology did not show statistically significant differences between the cell-treated and control IVDs. Conclusions Following transplantation of bone marrow stromal cells, NP tissue contained more PG than control discs. Although this result was promising, the rate and severity of degeneration in this goat disc injury were modest, suggesting that a more severe injury and a larger sample size is indicated for future studies to better define the utility of cell therapies in this model. PMID:20890267

  10. In Vivo Mouse Intervertebral Disc Degeneration Model Based on a New Histological Classification

    PubMed Central

    Ohnishi, Takashi; Sudo, Hideki; Iwasaki, Koji; Tsujimoto, Takeru; Ito, Yoichi M.; Iwasaki, Norimasa

    2016-01-01

    Although human intervertebral disc degeneration can lead to several spinal diseases, its pathogenesis remains unclear. This study aimed to create a new histological classification applicable to an in vivo mouse intervertebral disc degeneration model induced by needle puncture. One hundred six mice were operated and the L4/5 intervertebral disc was punctured with a 35- or 33-gauge needle. Micro-computed tomography scanning was performed, and the punctured region was confirmed. Evaluation was performed by using magnetic resonance imaging and histology by employing our classification scoring system. Our histological classification scores correlated well with the findings of magnetic resonance imaging and could detect degenerative progression, irrespective of the punctured region. However, the magnetic resonance imaging analysis revealed that there was no significant degenerative intervertebral disc change between the ventrally punctured and non-punctured control groups. To induce significant degeneration in the lumbar intervertebral discs, the central or dorsal region should be punctured instead of the ventral region. PMID:27482708

  11. Glucosamine Supplementation Demonstrates a Negative Effect On Intervertebral Disc Matrix in an Animal Model of Disc Degeneration

    PubMed Central

    Jacobs, Lloydine; Vo, Nam; Coehlo, J. Paulo; Dong, Qing; Bechara, Bernard; Woods, Barrett; Hempen, Eric; Hartman, Robert; Preuss, Harry; Balk, Judith; Kang, James; Sowa, Gwendolyn

    2013-01-01

    Study Design Laboratory based controlled in vivo study Objective To determine the in vivo effects of oral glucosamine sulfate on intervertebral disc degeneration Summary of Background Data Although glucosamine has demonstrated beneficial effect in articular cartilage, clinical benefit is uncertain. A CDC report from 2009 reported that many patients are using glucosamine supplementation for low back pain (LBP), without significant evidence to support its use. Because disc degeneration is a major contributor of LBP, we explored the effects of glucosamine on disc matrix homeostasis in an animal model of disc degeneration. Methods Eighteen skeletally mature New Zealand White rabbits were divided into four groups: control, annular puncture, glucosamine, and annular puncture+glucosamine. Glucosamine treated rabbits received daily oral supplementation with 107mg/day (weight based equivalent to human 1500mg/day). Annular puncture surgery involved puncturing the annulus fibrosus (AF) of 3 lumbar discs with a 16G needle to induce degeneration. Serial MRIs were obtained at 0, 4, 8, 12, and 20 weeks. Discs were harvested at 20 weeks for determination of glycosaminoglycan(GAG) content, relative gene expression measured by RT-PCR, and histological analyses. Results The MRI index and NP area of injured discs of glucosamine treated animals with annular puncture was found to be lower than that of degenerated discs from rabbits not supplemented with glucosamine. Consistent with this, decreased glycosaminoglycan was demonstrated in glucosamine fed animals, as determined by both histological and GAG content. Gene expression was consistent with a detrimental effect on matrix. Conclusions These data demonstrate that the net effect on matrix in an animal model in vivo, as measured by gene expression, MRI, histology, and total proteoglycan is anti-anabolic. This raises concern over this commonly used supplement, and future research is needed to establish the clinical relevance of these

  12. Model of Disc Degeneration in Rat Tail Induced Through a Vascular Isolation of Vertebral Endplates.

    PubMed

    Fernández-Susavila, Héctor; Pardo-Seco, Juan Pablo; Iglesias-Rey, Ramón; Sobrino, Tomás; Campos, Francisco; Díez-Ulloa, Máximo Alberto

    2017-05-25

    Back pain is a major health problem. The degenerative cascade of the spine begins in the intervertebral disc, due to an impairment in the blood supply through the vertebral endplates. Our objective was to develop a novel disc degeneration model based on these premises, akin to the process in humans, in contrast to other proposed models (puncture, enzyme injection, aberrant loads,…) Material and methods: 37 Sprague-Dawley rats, 2 arms: (a) histological (n = 17, one died), en- bloc sections, Van Gieson staining, (Nisimura-Mochida criteria) and also collagen VI staining (tissue oxidative stress), four animals were euthanized every 2 weeks (2-8); and (b) imaging (n = 20, six wound sloughs), MRI 9.4 Tesla protocol, sequential disc volumetric analysis (24 h-8 weeks) in all animals. Disc degeneration was induced by means of vascular isolation of tail discs endplates either from one side or both. Isolation from both sides caused a progressive degeneration of the disc (p < 0.001 vs. controls), bigger than isolation from one side (p < 0.01 vs. both sides and p < 0.05 vs. controls), as rated by volumetric reduction; furthermore, tissue structural changes (Nisimura-Mochida) and collagen VI deposition confirmed these results. the model here described represents a novel and translational tool that reproduces the intervertebral disc degeneration in a similar way to that taking place in human beings.

  13. New in vivo animal model to create intervertebral disc degeneration and to investigate the effects of therapeutic strategies to stimulate disc regeneration.

    PubMed

    Kroeber, Markus W; Unglaub, Frank; Wang, Haili; Schmid, Carsten; Thomsen, Marc; Nerlich, Andreas; Richter, Wiltrud

    2002-12-01

    A new rabbit model was developed that produces disc degeneration through the application of controlled and quantified axial mechanical load. To characterize the changes associated with disc degeneration, and to evaluate the feasibility of local transfer of agents to the compressed discs to stimulate disc regeneration. Studies have shown that accelerated degeneration of the intervertebral disc results from altered mechanical loading conditions. The development of methods for the prevention of disc degeneration and the restoration of disc tissue that has already degenerated is needed. New Zealand white rabbits (n = 33) were used for this study. The discs in five animals remained unloaded and served as controls, whereas in 28 animals the discs were axially compressed using a custom-made external loading device. After 1 (n = 7), 14 (n = 7), and 28 (n = 7) days of dynamic loading, or 28 (n = 7) days of loading followed by 28 days of unloaded recovery time, the animals were killed and the lumbar spine was harvested for tissue preparation. Disc height, disc morphology, cell viability, disc stiffness, and load to failure were measured. Recombinant adenovirus encoding for two different marker genes (Ad-Luciferase and Ad-LacZ) was injected into the discs in loaded specimens and the gene expression was measured. The unloaded intervertebral discs of the rabbits consisted of a layered anulus fibrosus, a cartilaginous endplate, and a nucleus pulposus comparable with those of humans. After 14 and 28 days of loading, the discs demonstrated a significant decrease in disc space. Histologically, disorganization of the architecture of the anulus occurred. The number of dead cells increased significantly in the anulus and cartilage endplate. These changes were not reversible after 28 days of unloading. The stiffness and the load to failure did not change significantly in the discs after 28 days of loading, as compared with the unloaded control discs. Adenovirus-mediated gene transfer

  14. A novel approach for the annulus needle puncture model of intervertebral disc degeneration in rabbits

    PubMed Central

    Lei, Tao; Zhang, Yuan; Zhou, Qiang; Luo, Xiaoji; Tang, Ke; Chen, Rongsheng; Yu, Chang; Quan, Zhengxue

    2017-01-01

    Objective: To create the rabbit animal model of intervertebral disc (IVD) degeneration by the annulus needle puncture technique through a novel transabdominal approach. Methods: Thirteen New Zealand White rabbits underwent annular puncture at the L3/4, L4/5, and L5/6 discs through a transabdominal approach. For a longitudinal study to assess changes in disc height over time, serial X-rays, T2-weighted magnetic resonance imaging (MRI) (T2WI), and T2 mapping MRI were performed pre-operation and at 2, 4, and 6 weeks after puncture. Three rabbits were randomly selected for histological evaluation at 4 weeks post-operation. In addition, the remaining rabbits underwent a second surgery at 6 weeks after puncture. Results: All rabbits underwent the initial and second surgeries successfully without nerve-related complications. The operations had no significant effects on the rabbit body weight, and partial mild intra-abdominal adhesions were found in only 1 rabbit. The punctured discs were confirmed to be those of interest post-surgery and displayed progressive degeneration in disc height index (%), T2WI, and T2 relaxation time over time. At 4 weeks after puncture, a histological analysis revealed notochordal cell loss from the nucleus pulposus, fibrocartilage filling the nucleus pulposus space, and annulus fibrosus disorganization. Conclusion: The annular needle puncture model established through a transabdominal approach, which demonstrates better visualization, exact identification, consistent degeneration degrees and minimal complications, is radiologically and histologically consistent with human IVD degeneration. T2 mapping MRI can quantitatively discriminate between grades of mild degeneration. PMID:28386320

  15. Biomechanical and rheological characterization of mild intervertebral disc degeneration in a large animal model.

    PubMed

    Detiger, Suzanne E L; Hoogendoorn, Roel J W; van der Veen, Albert J; van Royen, Barend J; Helder, Marco N; Koenderink, Gijsje H; Smit, Theo H

    2013-05-01

    Biomechanical properties of healthy and degenerated nucleus pulposus (NP) are thought to be important for future regenerative strategies for intervertebral disc (IVD) repair. However, which properties are pivotal as design criteria when developing NP replacement materials is ill understood. Therefore, we determined and compared segmental biomechanics and NP viscoelastic properties in normal and mildly degenerated discs. In eight goats, three lumbar IVDs were chemically degenerated using chondroitinase ABC (CABC), confirmed with radiography and MRI after euthanasia 12 weeks post-operative. Neutral zone (NZ) stiffness and range of motion (ROM) were determined sagitally, laterally, and rotationally for each spinal motion segment (SMS) using a mechanical testing device. NPs were isolated for oscillatory shear experiments; elastic and viscous shear moduli followed from the ratio between shear stress and strain. Water content was quantified by weighing before and after freeze-drying. Disc height on radiographs and signal intensity on MRI decreased (6% and 22%, respectively, p < 0.01) after CABC treatment, confirming that chemical degeneration provides a good model of disc degeneration. Furthermore, CABC-injected IVDs had significantly lower NZ stiffness and larger ROM in lateral bending (LB) and axial rotation (AR) than controls. Rheometry consistently revealed significantly lower (10-12%) viscoelastic moduli after mild degeneration within goats, though the inter-animal differences were relatively large (complex modulus ∼12 to 41 kPa). Relative water content in the NP was unaffected by CABC, remaining at ∼75%. These observations suggest that viscoelastic properties have a marginal influence on mechanical behavior of the whole SMS. Therefore, when developing replacement materials the focus should be on other design criteria, such as biochemical cues and swelling pressure. Copyright © 2012 Orthopaedic Research Society.

  16. The effects of human Wharton's jelly cell transplantation on the intervertebral disc in a canine disc degeneration model.

    PubMed

    Zhang, Yan; Tao, Hui; Gu, Tao; Zhou, Mingyue; Jia, Zhiwei; Jiang, Gangqiang; Chen, Chun; Han, Zhihua; Xu, Cheng; Wang, Deli; He, Qing; Ruan, Dike

    2015-08-27

    Cell-based therapy was a promising treatment method for disc degenerative diseases. Wharton's jelly cell (WJC) has been explored to cure various human diseases, while it still remains unknown about this MSC for disc repair. In our prior work, WJCs could differentiate into nucleus pulposus (NP)-like cells by co-culturing with NP cells in vitro. Thence, the aim of this study was further to investigate the survival and function of WJCs in vivo after transplantation into degenerated canine discs. WJCs were isolated from human umbilical cords and labeled with EGFP. The degeneration of L4-5, L5-6, and L6-7 discs of beagles was induced by aspirating the NP tissues. Four weeks after the operation, the injured discs were left to be no treatment at L4-5 (DS group), injected with 0.9 % saline at L5-6 (FS group), and transplanted with EGFP-labeled WJCs at L6-7 (TS group). In all animals, the intact disc L3-4 served as a control (CS group). The animals were followed up for 24 weeks after initial operation. Spine imaging was evaluated at 4, 8, 12, and 24 weeks, respectively. Histologic, biomechanics and gene expression analyses were performed at 24 weeks. Immunohistochemistry for aggrecan, types II collagen, SOX-9 was employed to investigate the matrix formation in the NP. The TS group showed a significantly smaller reduction in the disc height and T2-weighted signal intensity, and a better spinal segmental stability than DS and FS groups. Histologic assay demonstrated that WJCs were specifically detected in TS group at 24 weeks and the discs of TS group maintained a relatively well preserved structure as compared to the discs of DS and FS groups. Furthermore, real-time PCR and immunohistochemistry demonstrated that expressions of disc matrix genes, aggrecan, type II collagen, and SOX-9, were up-regulated in TS group compared to DS and FS groups. WJCs could not only survive in the degenerate IVDs, but also promote the disc matrix formation of aggrecan and type II collagen

  17. A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype.

    PubMed

    Hirata, Hiroaki; Yurube, Takashi; Kakutani, Kenichiro; Maeno, Koichiro; Takada, Toru; Yamamoto, Junya; Kurakawa, Takuto; Akisue, Toshihiro; Kuroda, Ryosuke; Kurosaka, Masahiro; Nishida, Kotaro

    2014-03-01

    The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell types-notochordal cells (NCs) and non-notochordal chondrocyte-like cells. In human discs, NCs are lost during adolescence, which is also when discs begin to show degenerative signs. However, little evidence exists regarding the link between NC disappearance and the pathogenesis of disc degeneration. To clarify this, a rat tail disc degeneration model induced by static compression at 1.3 MPa for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days. Radiography, MRI, and histomorphology showed degenerative disc findings in response to the compression period. Immunofluorescence displayed that the number of DAPI-positive NP cells decreased with compression; particularly, the decrease was notable in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, identified as NCs. The proportion of TUNEL-positive cells, which predominantly comprised non-NCs, increased with compression. Quantitative PCR demonstrated isolated mRNA up-regulation of ADAMTS-5 in the 1-day loaded group and MMP-3 in the 7-day loaded group. Aggrecan-1 and collagen type 2α-1 mRNA levels were down-regulated in both groups. This rat tail temporary static compression model, which exhibits decreased NC phenotype, increased apoptotic cell death, and imbalanced catabolic and anabolic gene expression, reproduces different stages of intervertebral disc degeneration.

  18. Notochordal cell disappearance and modes of apoptotic cell death in a rat tail static compression-induced disc degeneration model

    PubMed Central

    2014-01-01

    Introduction The intervertebral disc has a complex structure originating developmentally from both the mesenchyme and notochord. Notochordal cells disappear during adolescence, which is also when human discs begin to show degenerative signs. During degeneration later in life, disc cells decline because of apoptosis. Although many animal models have been developed to simulate human disc degeneration, few studies have explored the long-term changes in cell population and phenotype. Our objective was to elucidate the time-dependent notochordal cell disappearance and apoptotic cell death in a rat tail static compression-induced disc degeneration model. Methods Twenty-four 12-week-old male Sprague–Dawley rat tails were instrumented with an Ilizarov-type device and loaded statically at 1.3 MPa for up to 56 days. Loaded and distal-unloaded discs were harvested. Changes in cell number and phenotype were assessed with histomorphology and immunofluorescence. Apoptosis involvement was determined with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and immunohistochemistry. Results The number of disc nucleus pulposus and annulus fibrosus cells decreased with the loading period; particularly, the decrease was notable at day 7 in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, indicating notochordal origin. Subsequently, the proportion of cells positive for TUNEL and cleaved caspase-3, markers of apoptosis induction, increased from day 7 through day 56. Although the percentage of cells immunopositive for cleaved caspase-8, a marker of apoptosis initiation through the death-receptor pathway, increased only at day 7, the percentage of cells immunopositive for cleaved caspase-9 and p53-regulated apoptosis-inducing protein 1 (p53AIP1), markers of apoptosis initiation through the p53-mediated mitochondrial pathway, increased from day 7 through day 56. The percentage of cells immunopositive for B-cell lymphoma 2 (Bcl-2) and silent

  19. Quantitative T2 mapping to characterize the process of intervertebral disc degeneration in a rabbit model.

    PubMed

    Sun, Wei; Zhang, Kai; Zhao, Chang-qing; Ding, Wei; Yuan, Jun-jie; Sun, Qi; Sun, Xiao-jiang; Xie, You-zhuan; Li, Hua; Zhao, Jie

    2013-12-18

    To investigate the potential of T2 mapping for characterizing the process of intervertebral disc degeneration (IDD) in a rabbit model. Thirty-five rabbits underwent an annular stab to the L4/5 discs (L5/6 discs served as internal normal controls). Degenerative changes were graded according to the modified Thompson classification and quantified in T2 respectively at pre-operation, 1, 3, 6, 12 and 24 weeks postoperatively. After MRI analysis, expression analysis of aggrecan and type II collagen gene in nucleus pulposus (NP) was performed using real time polymerase chain reaction (real-time PCR). The longitudinal changes in NP T2 and gene expressions were studied by repeated measures and ANOVA, linear regression was performed for their correlations through the process of IDD. The reliability analysis of method of measurement of NP T2 was also performed. There was a strong inverse correlation between NP T2 and Thompson grades (r = -0.85). The decline of L4/5 NP T2 through 24 weeks was nonlinear, the most significant decrease was observed in 3 weeks postoperatively (P<0.05). The tendency was confirmed at gene expression levels. NP T2 correlated strongly with aggrecan (R² = 0.85, P<0.01) and type II collagen (R² = 0.78, P<0.01) gene expressions. The intraclass correlation coefficients for interobserver and intraobserver reliability were 0.963 and 0.977 respectively. NP T2 correlates well with aggrecan and type II collagen gene expressions. T2 mapping could act as a sensitive, noninvasive tool for quantitatively characterizing the process of IDD in longitudinal study, help better understanding of the pathophysiology of IDD, assist us to detect the degenerative cascade, and develop a T2-based quantification scale for evaluation of IDD and efficacy of therapeutic interventions.

  20. Inflammation in intervertebral disc degeneration and regeneration

    PubMed Central

    Molinos, Maria; Almeida, Catarina R.; Caldeira, Joana; Cunha, Carla; Gonçalves, Raquel M.; Barbosa, Mário A.

    2015-01-01

    Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players. PMID:25673296

  1. Cell therapy for the degenerating intervertebral disc.

    PubMed

    Tong, Wei; Lu, Zhouyu; Qin, Ling; Mauck, Robert L; Smith, Harvey E; Smith, Lachlan J; Malhotra, Neil R; Heyworth, Martin F; Caldera, Franklin; Enomoto-Iwamoto, Motomi; Zhang, Yejia

    2017-03-01

    Spinal conditions related to intervertebral disc (IVD) degeneration cost billions of dollars in the US annually. Despite the prevalence and soaring cost, there is no specific treatment that restores the physiological function of the diseased IVD. Thus, it is vital to develop new treatment strategies to repair the degenerating IVD. Persons with IVD degeneration without back pain or radicular leg pain often do not require any intervention. Only patients with severe back pain related to the IVD degeneration or biomechanical instability are likely candidates for cell therapy. The IVD progressively degenerates with age in humans, and strategies to repair the IVD depend on the stage of degeneration. Cell therapy and cell-based gene therapy aim to address moderate disc degeneration; advanced stage disease may require surgery. Studies involving autologous, allogeneic, and xenogeneic cells have all shown good survival of these cells in the IVD, confirming that the disc niche is an immunologically privileged site, permitting long-term survival of transplanted cells. All of the animal studies reviewed here reported some improvement in disc structure, and 2 studies showed attenuation of local inflammation. Among the 50 studies reviewed, 25 used some type of scaffold, and cell leakage is a consistently noted problem, though some studies showed reduced cell leakage. Hydrogel scaffolds may prevent cell leakage and provide biomechanical support until cells can become established matrix producers. However, these gels need to be optimized to prevent this leakage. Many animal models have been leveraged in this research space. Rabbit is the most frequently used model (28 of 50), followed by rat, pig, and dog. Sheep and goat IVDs resemble those of humans in size and in the absence of notochordal cells. Despite this advantage, there were only 2 sheep and 1 goat studies of 50 studies in this cohort. It is also unclear if a study in large animals is needed before clinical trials since

  2. Quantitative Pfirrmann Disc Degeneration Grading System to Overcome the Limitation of Pfirrmann Disc Degeneration Grade.

    PubMed

    Rim, Dae Cheol

    2016-03-01

    Pfirrmann disc degeneration grade is one of morphologic disc degeneration grading system and it was reliable on routine T2-weighted magnetic resonance (MR) images. The purpose of this study was to evaluate the agreement of Pfirrmann disc degeneration grade, and check the alternative technique of disc degeneration grading system. Fifteen volunteers (4 medical doctors related to spinal disease, 2 medical doctors not related to spinal disease, 6 nurses in spinal hospital, and 3 para-medicines) were included in this study. Three different digitalized MR images were provided all volunteers, and they checked Pfirrmann disc degeneration grade of each disc levels after careful listening to explanation. Indeed, all volunteers checked the signal intensity of disc degeneration at the points of nucleus pulposus (NP), disc membrane, ligaments, fat, and air to modify the quantitative Pfirrmann disc degeneration grade. Total 225 grade results of Pfirrmann disc degeneration grade and 405 signal intensity results of quantitative Pfirrmann disc degeneration grade were analyzed. Average interobserver agreement was "moderate (mean±standard deviation, 0.575±0.251)" from poor to excellent. Completely agreed levels of Pfirrmann disc degeneration grade were only 4 levels (26.67%), and the disagreement levels were observed in 11 levels; two different grades in 8 levels (53.33%) and three different grades in 3 levels (20%). Quantitative Pfirrmann disc degeneration showed relatively cluster distribution with the interobserver deviations of 0.41-1.56 at the ratio of NP and disc membrane, and it showed relatively good cluster and distribution indicating that the proposed grading system has good discrimination ability. Pfirrmann disc degeneration grade showed the limitation of different interobserver results, but this limitation could be overcome by using quantitative techniques of MR signal intensity. Further evaluation is needed to access its advantage and reliabilities.

  3. The molecular basis of intervertebral disc degeneration.

    PubMed

    Kepler, Christopher K; Ponnappan, Ravi K; Tannoury, Chadi A; Risbud, Marakand V; Anderson, David G

    2013-03-01

    Intervertebral disc (IVD) degeneration remains a clinically important condition for which treatment is costly and relatively ineffective. The molecular basis of degenerative disc disease has been an intense focus of research recently, which has greatly increased our understanding of the biology underlying this process. To review the current understanding of the molecular basis of disc degeneration. Review article. A literature review was performed to identify recent investigations and current knowledge regarding the molecular basis of IVD degeneration. The unique structural requirements and biochemical properties of the disc contribute to its propensity toward degeneration. Mounting evidence suggests that genetic factors account for up to 75% of individual susceptibility to IVD degeneration, far more than the environmental factors such as occupational exposure or smoking that were previously suspected to figure prominently in this process. Decreased extracellular matrix production, increased production of degradative enzymes, and increased expression of inflammatory cytokines contribute to the loss of structural integrity and accelerate IVD degeneration. Neurovascular ingrowth occurs, in part, because of the changing degenerative phenotype. A detailed understanding of the biology of IVD degeneration is essential to the design of therapeutic solutions to treat degenerative discs. Although significant advances have been made in explaining the biologic mediators of disc degeneration, the inhospitable biochemical environment of the IVD remains a challenging environment for biological therapies. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Regeneration of the intervertebral disc with nucleus pulposus cell-seeded collagen II/hyaluronan/chondroitin-6-sulfate tri-copolymer constructs in a rabbit disc degeneration model.

    PubMed

    Huang, Bo; Zhuang, Ying; Li, Chang-Qing; Liu, Lan-Tao; Zhou, Yue

    2011-12-15

    Advancement in tissue engineering provides a promising approach to recover the functionality of the degenerated intervertebral disc. In our study, a nucleus pulposus (NP) cell-seeded collagen II/hyaluronan/chondroitin-6-sulfate (CII/HyA/CS) tri-copolymer construct was implanted into the disc space directly after nucleotomy in a rabbit model. The aim of this study was to investigate whether the NP cell-seeded CII/HyA/CS tri-copolymer constructs could regenerate the degenerated disc in vivo after implantation into the rabbit nucleotomy model. Nucleotomy is one of the most prevalent surgical modalities to treat degenerative disc disease, which could achieve good short-term effects of pain relieve, whereas removal of the entire or partial NP changes the biomechanical characteristics of the remaining disc and the adjacent vertebral segments and a series of long-term complications such as accelerated annulus and the facet joints degeneration may ensue. Therefore, it is necessary to think about possible procedures immediately after the primary nucleotomy surgery to avoid these complications. NP cells isolated from thoracic and lumbar spines of New Zealand White rabbits of approximately 3 weeks of age and 1 kg in weight were labeled with a 5- (and-6) -carboxyflurescein diacetate succinimidyl ester (CFDA-SE) fluorescent dye and seeded within the CII/HyA/CS scaffold by a centrifugation method. After in vitro culture for 1 week, NP cell-seeded CII/HyA/CS tri-copolymer constructs were allografted into the disc defects of recipient rabbit immediately after nucleotomy of the lumbar spine. The Bradner Disc Index and the T2-weighted signal intensity index were determined using lateral plane radiographs and magnetic resonance imaging at 4, 12, and 24 weeks after the operation. Finally, the operated discs were explanted for gross morphological observation, histological evaluation, and cell viability assessment. Animals with only nucleotomy and cell-free CII/HyA/CS scaffold

  5. Cell transplantation in lumbar spine disc degeneration disease.

    PubMed

    Hohaus, C; Ganey, T M; Minkus, Y; Meisel, H J

    2008-12-01

    Low back pain is an extremely common symptom, affecting nearly three-quarters of the population sometime in their life. Given that disc herniation is thought to be an extension of progressive disc degeneration that attends the normal aging process, seeking an effective therapy that staves off disc degeneration has been considered a logical attempt to reduce back pain. The most apparent cellular and biochemical changes attributable to degeneration include a decrease in cell density in the disc that is accompanied by a reduction in synthesis of cartilage-specific extracellular matrix components. With this in mind, one therapeutic strategy would be to replace, regenerate, or augment the intervertebral disc cell population, with a goal of correcting matrix insufficiencies and restoring normal segment biomechanics. Biological restoration through the use of autologous disc chondrocyte transplantation offers a potential to achieve functional integration of disc metabolism and mechanics. We designed an animal study using the dog as our model to investigate this hypothesis by transplantation of autologous disc-derived chondrocytes into degenerated intervertebral discs. As a result we demonstrated that disc cells remained viable after transplantation; transplanted disc cells produced an extracellular matrix that contained components similar to normal intervertebral disc tissue; a statistically significant correlation between transplanting cells and retention of disc height could displayed. Following these results the Euro Disc Randomized Trial was initiated to embrace a representative patient group with persistent symptoms that had not responded to conservative treatment where an indication for surgical treatment was given. In the interim analyses we evaluated that patients who received autologous disc cell transplantation had greater pain reduction at 2 years compared with patients who did not receive cells following their discectomy surgery and discs in patients that

  6. Notochord Cells in Intervertebral Disc Development and Degeneration

    PubMed Central

    McCann, Matthew R.; Séguin, Cheryle A.

    2016-01-01

    The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of the intervertebral disc is thought to be an initiating factor for back pain. Due to a lack of understanding of the pathways that govern disc degeneration, there are currently no disease-modifying treatments to delay or prevent degenerative disc disease. This review presents an overview of our current understanding of the developmental processes that regulate intervertebral disc formation, with particular emphasis on the role of the notochord and notochord-derived cells in disc homeostasis and how their loss can result in degeneration. We then describe the role of small animal models in understanding the development of the disc and their use to interrogate disc degeneration and associated pathologies. Finally, we highlight essential development pathways that are associated with disc degeneration and/or implicated in the reparative response of the tissue that might serve as targets for future therapeutic approaches. PMID:27252900

  7. RADIOLOGICAL ANALYSIS OF EXPERIMENTAL DISC DEGENERATION IN RABBITS

    PubMed Central

    Vialle, Emiliano; Vialle, Luiz Roberto; Arruda, André de Oliveira; Riet, Ricardo Nascimento; Krieger, Antônio Bernardo de Queiroz

    2015-01-01

    Objective: To validate radiographic evaluation of a rabbit model for disc degeneration. Methods: Lumbar intervertebral discs of New Zealand rabbits were stabbed three times with a 18G needle at a limited depth of 5mm, through lateral approach. Serial radiographic images were taken on the early pre-and postoperative periods, and after four, eight and 12 weeks of the procedure, with subsequent analysis of disc height, osteophyte formation, endplate sclerosis, and presence of disc degeneration. The statistical analysis of data was validated by the Kappa coefficient, with a confidence interval (CI) of 95%. Results: A significant reduction of disc space was found on AP X-ray images after 12 postoperative weeks, with Kappa = 0.489 for CI 95% (0.25-0.72) with p < 0.001. X-ray signs of disc degeneration also presented Kappa = 0.63 for CI 95% (0.39-0.86) with p < 0.001. The remaining assessed criteria showed positive results, but with a lower Kappa value. Conclusion: The disc degeneration model using rabbits as proposed in this study was shown to be feasible, with positive X-ray correlation between pre- and postoperative images, validating the potential to induce disc degeneration in this animal model for future studies. PMID:27022512

  8. Development and Kinematic Verification of a Finite Element Model for the Lumbar Spine: Application to Disc Degeneration

    PubMed Central

    Ibarz, Elena; Herrera, Antonio

    2013-01-01

    The knowledge of the lumbar spine biomechanics is essential for clinical applications. Due to the difficulties to experiment on living people and the irregular results published, simulation based on finite elements (FE) has been developed, making it possible to adequately reproduce the biomechanics of the lumbar spine. A 3D FE model of the complete lumbar spine (vertebrae, discs, and ligaments) has been developed. To verify the model, radiological images (X-rays) were taken over a group of 25 healthy, male individuals with average age of 27.4 and average weight of 78.6 kg with the corresponding informed consent. A maximum angle of 34.40° is achieved in flexion and of 35.58° in extension with a flexion-extension angle of 69.98°. The radiological measurements were 33.94 ± 4.91°, 38.73 ± 4.29°, and 72.67°, respectively. In lateral bending, the maximum angles were 19.33° and 23.40 ± 2.39, respectively. In rotation a maximum angle of 9.96° was obtained. The model incorporates a precise geometrical characterization of several elements (vertebrae, discs, and ligaments), respecting anatomical features and being capable of reproducing a wide range of physiological movements. Application to disc degeneration (L5-S1) allows predicting the affection in the mobility of the different lumbar segments, by means of parametric studies for different ranges of degeneration. PMID:23509766

  9. Can vertebral density changes be explained by intervertebral disc degeneration?

    PubMed

    Homminga, Jasper; Aquarius, Rene; Bulsink, Vera E; Jansen, Christiaan T J; Verdonschot, Nico

    2012-05-01

    One of the major problems facing the elderly spine is the occurrence of vertebral fractures due to low bone mass. Although typically attributed to osteoporosis, disc degeneration has also been suggested to play a role in vertebral fractures. Existing bone adaptation theories and simulations may explain the biomechanical pathway from a degenerated disc to an increased fracture risk. A finite element model of a lumbar segment was created and calibrated. Subsequently the disc properties were varied to represent either a healthy or degenerated disc and the resulting bone adaptation was simulated. Disc degeneration resulted in a shift of load from the nucleus to the annulus. The resulting bone adaptation led to a dramatically reduced density of the trabecular core and to an increased density in the vertebral walls. Degeneration of just the nucleus, and in particular the dehydration of the nucleus, resulted in most of this bone density change. Additional annulus degeneration had much less of an effect on the density values. The density decrease in the trabecular core as seen in this study matches clinical observations. Therefore, bone remodeling theories can assists in explaining the potential synergistic effects of disc degeneration and osteoporotis in the occurrence of vertebral fractures. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

  10. MRI evaluation of spontaneous intervertebral disc degeneration in the alpaca cervical spine.

    PubMed

    Stolworthy, Dean K; Bowden, Anton E; Roeder, Beverly L; Robinson, Todd F; Holland, Jacob G; Christensen, S Loyd; Beatty, Amanda M; Bridgewater, Laura C; Eggett, Dennis L; Wendel, John D; Stieger-Vanegas, Susanne M; Taylor, Meredith D

    2015-12-01

    Animal models have historically provided an appropriate benchmark for understanding human pathology, treatment, and healing, but few animals are known to naturally develop intervertebral disc degeneration. The study of degenerative disc disease and its treatment would greatly benefit from a more comprehensive, and comparable animal model. Alpacas have recently been presented as a potential large animal model of intervertebral disc degeneration due to similarities in spinal posture, disc size, biomechanical flexibility, and natural disc pathology. This research further investigated alpacas by determining the prevalence of intervertebral disc degeneration among an aging alpaca population. Twenty healthy female alpacas comprised two age subgroups (5 young: 2-6 years; and 15 older: 10+ years) and were rated according to the Pfirrmann-grade for degeneration of the cervical intervertebral discs. Incidence rates of degeneration showed strong correlations with age and spinal level: younger alpacas were nearly immune to developing disc degeneration, and in older animals, disc degeneration had an increased incidence rate and severity at lower cervical levels. Advanced disc degeneration was present in at least one of the cervical intervertebral discs of 47% of the older alpacas, and it was most common at the two lowest cervical intervertebral discs. The prevalence of intervertebral disc degeneration encourages further investigation and application of the lower cervical spine of alpacas and similar camelids as a large animal model of intervertebral disc degeneration.

  11. Effect of Survivin gene therapy via lentivirus vector on the course of intervertebral disc degeneration in an in vivo rabbit model

    PubMed Central

    Yue, Bin; Lin, Yazhou; Ma, Xuexiao; Zhang, Guoqing; Chen, Bohua

    2016-01-01

    The aim of the current study was to use gene therapy to attenuate or reverse the degenerative process within the intervertabral disc. The effect of survivin gene therapy via lentiviral vector transfection on the course of intervertebral disc degeneration was investigated in the current study in an in vivo rabbit model. A total of 15 skeletally mature female New Zealand White rabbits were randomly divided into three groups: Punctured blank control group (group A, n=5), punctured empty vector control group (group B, n=5) and the treatment group (group C, n=5). Computed tomography-guided puncture was performed at the L3-L4 and L4-L5 discs, in accordance with a previously validated rabbit annulotomy model for intervertebral disc degeneration. After 3 weeks, a lentiviral vector (LV) carrying survivin was injected into the nucleus pulposus. The results demonstrated that through magnetic resonance imaging, histology, gene expression, protein content and apoptosis analyses, group A and B were observed to exhibit disc degeneration, which increased over time, and no significant difference was observed between the two groups (P>0.05). However, there was reduced disc degeneration in group C compared with the punctured control groups, and the difference was statistically significant (P<0.05). Overall, the results of the present study demonstrated that injection of the LV carrying survivin into punctured rabbit intervertebral discs acted to delay changes associated with the degeneration of the discs. Although data from animal models should be extrapolated to the human condition with caution, the present study suggests potential for the use of gene therapy to decelerate disc degeneration. PMID:27748828

  12. Behavioral signs of axial low back pain and motor impairment correlate with the severity of intervertebral disc degeneration in a mouse model.

    PubMed

    Millecamps, Magali; Czerminski, Jan T; Mathieu, Axel P; Stone, Laura S

    2015-12-01

    Chronic low back pain is debilitating and difficult to treat. Depending on the etiology, responses to treatments vary widely. Although chronic low back pain is frequently related to intervertebral disc degeneration, the relationship between disc degeneration severity and clinical symptoms are still poorly understood. In humans, studies investigating the relationship between disc degeneration severity and low back pain are limited by the difficulty of obtaining disc samples from well-characterized patients and pain-free controls. We have previously described the secreted protein, acidic, rich in cysteine (SPARC)-null mouse model of chronic low back pain. SPARC is a matricellular protein involved in regulating the assembly and composition of extracellular matrix. The SPARC-null mice develop age-dependent disc degeneration of increasing severity accompanied by behavioral signs suggestive of axial low back pain, radiating leg pain, and motor impairment. The existence of this model allows for examination of the relationships between clinical symptoms in vivo and pathological signs of disc degeneration ex vivo. The goal of this study was to explore the relationship between behavioral signs of pain and the severity of lumbar disc degeneration using the SPARC-null mouse model of disc degeneration-related low back pain. This study used a cross-sectional, multiple-cohort behavioral and histological study of disc degeneration and behavioral symptoms in a mouse model of low back pain associated with disc degeneration. SPARC-null and wild-type control mice ranging from 6 to 78 weeks of age were used in this study. The severity of disc degeneration was determined by ex vivo analysis of the lumbar spine using colorimetric histological staining and a scoring system adapted from the Pfirrmann scale. Behavioral signs of axial low back pain, radiating leg pain, and motor impairment were quantified as tolerance to axial stretching in the grip force assay, hypersensitivity to cold or

  13. Decellularized allogeneic intervertebral disc: natural biomaterials for regenerating disc degeneration

    PubMed Central

    Hu, Zhijun; Chen, Kai; Shan, Zhi; Chen, Shuai; Wang, Jiying; Mo, Jian; Ma, Jianjun; Xu, Wenbing; Qin, An; Fan, Shunwu

    2016-01-01

    Intervertebral disc degeneration is associated with back pain and disc herniation. This study established a modified protocol for intervertebral disc (IVD) decellularization and prepared its extracellular matrix (ECM). By culturing mesenchymal stem cells (MSCs)(3, 7, 14 and 21 days) and human degenerative IVD cells (7 days) in the ECM, implanting it subcutaneously in rabbit and injecting ECM microparticles into degenerative disc, the biological safety and efficacy of decellularized IVD was evaluated both in vitro and in vivo. Here, we demonstrated that cellular components can be removed completely after decellularization and maximally retain the structure and biomechanics of native IVD. We revealed that allogeneic ECM did not evoke any apparent inflammatory reaction in vivo and no cytotoxicity was found in vitro. Moreover, IVD ECM can induce differentiation of MSCs into IVD-like cells in vitro. Furthermore, allogeneic ECM microparticles are effective on the treatment of rabbit disc degeneration in vivo. In conclusion, our study developed an optimized method for IVD decellularization and we proved decellularized IVD is safe and effective for the treatment of degenerated disc diseases. PMID:26933821

  14. 1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model.

    PubMed

    Osti, O L; Vernon-Roberts, B; Fraser, R D

    1990-08-01

    An animal model was developed to test the hypothesis that discrete peripheral tears within the anulus lead to secondary degenerative changes in other disc components. In 21 adult sheep, a cut was made in the left anterolateral anulus of three randomly selected lumbar discs. The cut was parallel and adjacent to the inferior end-plate, and had a controlled depth of 5 mm. This left the inner third of the anulus and the nucleus pulposus intact and closely reproduced the rim Lear lesion described by Schmorl. Animals were randomly allocated to different groups in relation to the length of time interval between operation and death, varying from 1 to 18 months. At death, the lumbar spine was cut into individual joint units and each disc sectioned into six parasagittal slabs. After observation of the slabs under the dissecting microscope, two of the six slabs, the one containing the anulus lesion and a contralateral, were processed for histology. The results of this study suggest that, despite the great care taken at operation to ensure that the inner anulus was left intact, progressive failure of the inner anulus was seen in all sheep and occurred in the majority of discs between 4 and 12 months after the operation. Although the outermost anulus showed the ability to heal, the defect induced by the cut led initially to deformation and bulging of the collagen bundles, and eventually to inner extension of the tear and complete failure. These findings suggest that discrete tears of the outer anulus may have a role in the formation of concentric clefts and in accelerating the development of radiating clefts. Peripheral tears of the anulus fibrosus therefore may play an important role in the degeneration of the intervertebral joint complex.

  15. A papain-induced disc degeneration model for the assessment of thermo-reversible hydrogel-cells therapeutic approach.

    PubMed

    Malonzo, C; Chan, S C W; Kabiri, A; Eglin, D; Grad, S; Bonél, H M; Benneker, L M; Gantenbein-Ritter, B

    2015-12-01

    Nucleus pulposus (NP) regeneration by the application of injectable cell-embedded hydrogels is an appealing approach for tissue engineering. We investigated a thermo-reversible hydrogel (TR-HG), based on a modified polysaccharide with a thermo-reversible polyamide [poly(N-isopropylacrylamide), pNIPAM], which is made to behave as a liquid at room temperature and hardens at > 32 °C. In order to test the hydrogel, a papain-induced bovine caudal disc degeneration model (PDDM), creating a cavity in the NP, was employed. Human mesenchymal stem cells (hMSCs) or autologous bovine NP cells (bNPCs) were seeded in TR-HG; hMSCs were additionally preconditioned with rhGDF-5 for 7 days. Then, TR-HG was reversed to a fluid and the cell suspension injected into the PDDM and kept under static loading for 7 days. Experimental design was: (D1) fresh disc control + PBS injection; (D2) PDDM + PBS injection; (D3) PDDM + TR-HG (material control); (D4) PDDM + TR-HG + bNPCs; (D5) PDDM + TR-HG + hMSCs. Magnetic resonance imaging performed before and after loading, on days 9 and 16, allowed imaging of the hydrogel-filled PDDM and assessment of disc height and volume changes. In gel-injected discs the NP region showed a major drop in volume and disc height during culture under static load. The RT-PCR results of injected hMSCs showed significant upregulation of ACAN, COL2A1, VCAN and SOX9 during culture in the disc cavity, whereas the gene expression profile of NP cells remained unchanged. The cell viability of injected cells (NPCs or hMSCs) was maintained at over 86% in 3D culture and dropped to ~72% after organ culture. Our results underline the need for load-bearing hydrogels that are also cyto-compatible.

  16. Inflammatory profiles in canine intervertebral disc degeneration.

    PubMed

    Willems, Nicole; Tellegen, Anna R; Bergknut, Niklas; Creemers, Laura B; Wolfswinkel, Jeannette; Freudigmann, Christian; Benz, Karin; Grinwis, Guy C M; Tryfonidou, Marianna A; Meij, Björn P

    2016-01-13

    Intervertebral disc (IVD) disease is a common spinal disorder in dogs and degeneration and inflammation are significant components of the pathological cascade. Only limited studies have studied the cytokine and chemokine profiles in IVD degeneration in dogs, and mainly focused on gene expression. A better understanding is needed in order to develop biological therapies that address both pain and degeneration in IVD disease. Therefore, in this study, we determined the levels of prostaglandin E2 (PGE2), cytokines, chemokines, and matrix components in IVDs from chondrodystrophic (CD) and non-chondrodystrophic (NCD) dogs with and without clinical signs of IVD disease, and correlated these to degeneration grade (according to Pfirrmann), or herniation type (according to Hansen). In addition, we investigated cyclooxygenase 2 (COX-2) expression and signs of inflammation in histological IVD samples of CD and NCD dogs. PGE2 levels were significantly higher in the nucleus pulposus (NP) of degenerated IVDs compared with non-degenerated IVDs, and in herniated IVDs from NCD dogs compared with non-herniated IVDs of NCD dogs. COX-2 expression in the NP and annulus fibrosus (AF), and proliferation of fibroblasts and numbers of macrophages in the AF significantly increased with increased degeneration grade. GAG content did not significantly change with degeneration grade or herniation type. Cytokines interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, immune protein (IP)-10, tumor necrosis factor (TNF)-α, and granulocyte macrophage colony-stimulating factor (GM-CSF) were not detectable in the samples. Chemokine (C-C) motif ligand (CCL)2 levels in the NP from extruded samples were significantly higher compared with the AF of these samples and the NP from protrusion samples. PGE2 levels and CCL2 levels in degenerated and herniated IVDs were significantly higher compared with non-degenerated and non-herniated IVDs. COX-2 expression in the NP and AF and reactive changes in the

  17. Disc degeneration-related clinical phenotypes.

    PubMed

    Battié, Michele C; Lazáry, Aron; Fairbank, Jeremy; Eisenstein, Stephen; Heywood, Chris; Brayda-Bruno, Marco; Varga, Péter Pál; McCall, Iain

    2014-06-01

    The phenotype, or observable trait of interest, is at the core of studies identifying associated genetic variants and their functional pathways, as well as diagnostics. Yet, despite remarkable technological developments in genotyping and progress in genetic research, relatively little attention has been paid to the equally important issue of phenotype. This is especially true for disc degeneration-related disorders, and the concept of degenerative disc disease, in particular, where there is little consensus or uniformity of definition. Greater attention and rigour are clearly needed in the development of disc degeneration-related clinical phenotypes if we are to see more rapid advancements in knowledge of this area. When selecting phenotypes, a basic decision is whether to focus directly on the complex clinical phenotype (e.g. the clinical syndrome of spinal stenosis), which is ultimately of interest, or an intermediate phenotype (e.g. dural sac cross-sectional area). While both have advantages, it cannot be assumed that associated gene variants will be similarly relevant to both. Among other considerations are factors influencing phenotype identification, comorbidities that are often present, and measurement issues. Genodisc, the European research consortium project on disc-related clinical pathologies has adopted a strategy that will allow for the careful characterisation and examination of both the complex clinical phenotypes of interest and their components.

  18. Protective effect of ligustrazine on lumbar intervertebral disc degeneration of rats induced by prolonged upright posture.

    PubMed

    Liang, Qian-Qian; Ding, Dao-Fang; Xi, Zhi-Jie; Chen, Yan; Li, Chen-Guang; Liu, Shu-Fen; Lu, Sheng; Zhao, Yong-Jian; Shi, Qi; Wang, Yong-Jun

    2014-01-01

    Most chronic low back pain is the result of degeneration of the lumbar intervertebral disc. Ligustrazine, an alkaloid from Chuanxiong, reportedly is able to relieve pain, suppress inflammation, and treat osteoarthritis and it has the protective effect on cartilage and chondrocytes. Therefore, we asked whether ligustrazine could reduce intervertebral disc degeneration. To determine the effect of ligustrazine on disc degeneration, we applied a rat model. The intervertebral disc degeneration of the rats was induced by prolonged upright posture. We found that pretreatment with ligustrazine for 1 month recovered the structural distortion of the degenerative disc; inhibited the expression of type X collagen, matrix metalloproteinase (MMP)-13, and MMP3; upregulated type II collagen; and decreased IL-1 β , cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) expression. In conclusion, ligustrazine is a promising agent for treating lumbar intervertebral disc degeneration disease.

  19. Intervertebral disc degeneration: evidence for two distinct phenotypes

    PubMed Central

    Adams, Michael A; Dolan, Patricia

    2012-01-01

    We review the evidence that there are two types of disc degeneration. ‘Endplate-driven’ disc degeneration involves endplate defects and inwards collapse of the annulus, has a high heritability, mostly affects discs in the upper lumbar and thoracic spine, often starts to develop before age 30 years, usually leads to moderate back pain, and is associated with compressive injuries such as a fall on the buttocks. ‘Annulus-driven’ disc degeneration involves a radial fissure and/or a disc prolapse, has a low heritability, mostly affects discs in the lower lumbar spine, develops progressively after age 30 years, usually leads to severe back pain and sciatica, and is associated with repetitive bending and lifting. The structural defects which initiate the two processes both act to decompress the disc nucleus, making it less likely that the other defect could occur subsequently, and in this sense the two disc degeneration phenotypes can be viewed as distinct. PMID:22881295

  20. The effects of anthropometrics, lifting strength, and physical activities in disc degeneration.

    PubMed

    Videman, Tapio; Levälahti, Esko; Battié, Michele C

    2007-06-01

    A cross-sectional study design was used. The objective was to examine the influences of body anthropometrics, axial disc area, and lifting strength on disc degeneration and to compare these with the effects of lifetime physical demands and age. Although recent studies have shown that heredity is a dominant factor in disc degeneration, the common notion that occupational physical loading is the major risk factor persists. However, substantial variations in disc degeneration, particularly at the lowest lumbar levels, remain unexplained by heredity or occupational physical demands. Univariate methods and stepwise multiple regression modeling were used to estimate associations of body height, weight, fat content, axial disc area, isokinetic lifting performance, and lifetime routine physical activities at work and leisure with disc height narrowing and disc signal (in T2 images) based on lumbar MRIs. These data were available from a population sample of 600 men, 35 to 70 years of age. Lower disc signal, representing disc desiccation, was associated with higher age, lower body mass and lifting strength, and larger axial disc area. Of the variance in disc signal, age explained 8.0% (P < 0.001) and body weight/axial disc area, isokinetic lifting strength, and occupational lifting history added 3.9%, 2.3%, and 1.3%, respectively. Greater disc narrowing was associated with higher age, larger axial disc area, and higher occupational physical loading. Of the variance in disc narrowing, age accounted for 3.8% (P < 0.001); axial disc area and occupational loading added 1.9% (P < 0.004) and 1.3% (P < 0.007), respectively. Body weight, lifting strength, and axial disc area were more highly associated with disc degeneration than occupational and leisure physical activity histories, although all had modest influences. Furthermore, higher body mass, greater lifting strength, and heavier work were all associated with more disc height narrowing but less disc desiccation contrary to

  1. Pathophysiological basis of lumbar disc degeneration: imaging analysis.

    PubMed

    Ostrum, B J; Romy, M; Swartz, J D

    1993-12-01

    This article provides a brief synopsis of the pathoanatomic basis of disc degeneration. An attempt is made to correlate CT, MR and CT discographic findings. The T2-weighted sagittal images are the most sensitive for evaluating disc degeneration. The contour changes on axial CT and MR scans are sensitive for abnormalities but not always specific. The CT discogram adds information unavailable by other imaging methods pertaining to the internal architecture of the disc. It additionally defines focal nuclear herniations and also is helpful in evaluating the stage of disc degeneration.

  2. Genetic Factors in Intervertebral Disc Degeneration

    PubMed Central

    Feng, Yi; Egan, Brian; Wang, Jinxi

    2016-01-01

    Low back pain (LBP) is a major cause of disability and imposes huge economic burdens on human society worldwide. Among many factors responsible for LBP, intervertebral disc degeneration (IDD) is the most common disorder and is a target for intervention. The etiology of IDD is complex and its mechanism is still not completely understood. Many factors such as aging, spine deformities and diseases, spine injuries, and genetic factors are involved in the pathogenesis of IDD. In this review, we will focus on the recent advances in studies on the most promising and extensively examined genetic factors associated with IDD in humans. A number of genetic defects have been correlated with structural and functional changes within the intervertebral disc (IVD), which may compromise the disc’s mechanical properties and metabolic activities. These genetic and proteomic studies have begun to shed light on the molecular basis of IDD, suggesting that genetic factors are important contributors to the onset and progression of IDD. By continuing to improve our understanding of the molecular mechanisms of IDD, specific early diagnosis and more effective treatments for this disabling disease will be possible in the future. PMID:27617275

  3. Fibroblast Transplantation Results to the Degenerated Rabbit Lumbar Intervertebral Discs.

    PubMed

    Ural, Ibrahim Halil; Alptekin, Kerem; Ketenci, Aysegul; Solakoglu, Seyhun; Alpak, Hasan; Özyalçın, Süleyman

    2017-01-01

    Our study is an analysis of the histological and radiological changes in degenerated lumbar intervertebral discs, after transplantation of fibroblasts in rabbits. With that study we aimed to show the viability of the fibroblasts injected to the degenerated discs, and observe their potential for further studies. The apoptosis of the cell is one of the factors at the disc degeneration process. Fibroblasts may act as mesenchymal stem cells at the tissue to which they are injected and they may replace the apoptotic cells. The nucleus pulposus of the discs from eight rabbits were aspirated under scopic guidance to induce disc degeneration. One month later, cultured fibroblasts, which had been taken from the skin, were injected into the disc. The viability and the potential of the injected cells for reproduction were studied histologically and radiologically. Cellular formations and organizations indicating to the histological recovery were observed at the discs to which fibroblasts were transplanted. The histological findings of the discs to which no fibroblasts were transplanted, did not show any histological recovery. Radiologically, no finding of the improvement was found in both groups. The fibroblasts injected to the degenerated discs are viable. The findings of improvement, observed in this study, suggest that fibroblast transplantation could be an effective method of therapy for the prevention or for the retardation of the degenerative disease of the discs.

  4. Fibroblast Transplantation Results to the Degenerated Rabbit Lumbar Intervertebral Discs

    PubMed Central

    Ural, Ibrahim Halil; Alptekin, Kerem; Ketenci, Aysegul; Solakoglu, Seyhun; Alpak, Hasan; Özyalçın, Süleyman

    2017-01-01

    Background: Our study is an analysis of the histological and radiological changes in degenerated lumbar intervertebral discs, after transplantation of fibroblasts in rabbits. With that study we aimed to show the viability of the fibroblasts injected to the degenerated discs, and observe their potential for further studies. Method: The apoptosis of the cell is one of the factors at the disc degeneration process. Fibroblasts may act as mesenchymal stem cells at the tissue to which they are injected and they may replace the apoptotic cells. The nucleus pulposus of the discs from eight rabbits were aspirated under scopic guidance to induce disc degeneration. Results: One month later, cultured fibroblasts, which had been taken from the skin, were injected into the disc. The viability and the potential of the injected cells for reproduction were studied histologically and radiologically. Cellular formations and organizations indicating to the histological recovery were observed at the discs to which fibroblasts were transplanted. The histological findings of the discs to which no fibroblasts were transplanted, did not show any histological recovery. Radiologically, no finding of the improvement was found in both groups. The fibroblasts injected to the degenerated discs are viable. Conclusion: The findings of improvement, observed in this study, suggest that fibroblast transplantation could be an effective method of therapy for the prevention or for the retardation of the degenerative disease of the discs. PMID:28603572

  5. Simulation of the Progression of Intervertebral Disc Degeneration due to Decreased Nutrition Supply

    PubMed Central

    Gu, Weiyong; Zhu, Qiaoqiao; Gao, Xin; Brown, Mark D.

    2014-01-01

    Study Design Simulate the progression of human disc degeneration. Objective The objective of this study was to quantitatively analyze and simulate the changes in cell density, nutrition level, proteoglycan content, water content, and volume change during human disc degeneration using a numerical method. Summary of Background Data Understanding the etiology and progression of intervertebral disc (IVD) degeneration is crucial for developing effective treatment strategies for IVD-degeneration related diseases. During tissue degeneration, the disc undergoes losses of cell viability and activities, changes in extracellular matrix composition and structure, and compromise of the tissue-level integrity and function, which is significantly influenced by the inter-coupled biological, chemical, electrical, and mechanical signals in the disc. Characterizing these signals in human discs in vivo is difficult. Methods A realistic 3D finite element model of the human IVD was developed based on biomechano-electrochemical continuum mixture theory. The theoretical framework and the constitutive relationships were all biophysics based. All the material properties were obtained from experimental results. The cell-mediated disc degeneration process caused by lowered nutrition levels at disc boundaries was simulated and validated by comparing with experimental results. Results Cell density reached equilibrium state in 30 days after reduced nutrition supply at the disc boundary, while the proteoglycan (PG) and water contents reached a new equilibrium state in 55 years. The simulated results for the distributions of PG and water contents within the disc were consistent with the results measured in the literature, except for the distribution of PG content in the sagittal direction. Conclusions Poor nutrition supply has a long-term effect on disc degeneration. PMID:25188596

  6. Lumbar intervertebral disc degeneration and related factors in Korean firefighters

    PubMed Central

    Jang, Tae-Won; Ahn, Yeon-Soon; Byun, Junsu; Lee, Jong-In; Kim, Kun-Hyung; Kim, Youngki; Song, Han-Soo; Lee, Chul-Gab; Kwon, Young-Jun; Yoon, Jin-Ha; Jeong, Kyoungsook

    2016-01-01

    Objectives The job of firefighting can cause lumbar burden and low back pain. This study aimed to identify the association between age and lumbar intervertebral disc degeneration and whether the association differs between field and administrative (non-field) firefighters. Methods Subjects were selected using a stratified random sampling method. Firefighters were stratified by geographic area, gender, age and type of job. First, 25 fire stations were randomly sampled considering regional distribution. Then firefighters were stratified by gender, age and their job and randomly selected among the strata. A questionnaire survey and MRI scans were performed, and then four radiologists used Pfirrmann classification methods to determine the grade of lumbar intervertebral disc degeneration. Results Pfirrmann grade increased with lumbar intervertebral disc level. Analysis of covariance showed that age was significantly associated with lumbar intervertebral disc degeneration (p<0.05). The value of β (parameter estimate) was positive at all lumbar intervertebral disc levels and was higher in the field group than in the administrative group at each level. In logistic regression analysis, type of job was statistically significant only with regard to the L4–5 intervertebral disc (OR 3.498, 95% CI 1.241 to 9.860). Conclusions Lumbar intervertebral disc degeneration is associated with age, and field work such as firefighting, emergency and rescue may accelerate degeneration in the L4–5 intervertebral disc. The effects of field work on lumbar intervertebral disc degeneration were not clear in discs other than at the level L4–5. PMID:27354080

  7. [Controlled distraction as a therapeutic option in moderate degeneration of the intervertebral disc -- an in vivo study in the rabbit-spine model].

    PubMed

    Unglaub, F; Guehring, T; Omlor, G; Lorenz, H; Carstens, C; Kroeber, M W

    2006-01-01

    The aim of this study was to investigate the effects of temporary distraction on a degenerated intervertebral disc to characterize regenerative changes associated with disc distraction. New Zealand white rabbits (n = 32) were used for this experimental animal study. The rabbits were randomly assigned to one of five groups. 6 animals were loaded for 28 days using a custom-made external loading device to stimulate disc degeneration (G2). In 6 animals the discs were first loaded for 28 days and after 28 days loading time the discs in six animals were treated as dynamic distraction with an external distraction device (G1). In six animals the discs were distracted for 28 days without previous loading (G5) and in six animals the discs were loaded for 28 days and afterwards the loading device was removed for 28 days for recovery without distraction (G3). Six animals were sham operated (G4) without application of axial load. After 28 to 56 days loading and distraction time, the animals were sacrificed and the lumbar spine was harvested for histological and radiographic analysis. Histology was performed according to a degeneration score and disc height was calculated radiographically. For the cell viability examination, the number of apoptotic cells was determined. After 28 days of loading (G2), the discs showed a significant decrease in disc space of the treated segment. Histologically, a disorganization of the architecture of the annulus occurred. The number of dead cells increased significantly in the annulus and cartilage endplate. These changes were reversible after 28 days of distraction (G1). The disc thickness increased significantly to physiological levels as compared to the specimens from the 28 days loading group without distraction. Histologically, the discs showed signs of tissue regeneration after 28 days of distraction (G1). The number of apoptotic cells decreased significantly in comparison to the loaded discs without distraction (G2). The results of this

  8. Effect of disc degeneration on the muscle recruitment pattern in upright posture: a computational analysis.

    PubMed

    Kim, Young Eun; Choi, Hae Won

    2015-01-01

    Based on the sensor driving control mechanism model, the effect of disc degeneration on the trunk muscle recruitment (TMR) pattern was analysed in erect standing posture. A previously developed computational model was used for this analysis, with modifications incorporating the T12-L1 motion segment and additional muscle fascicles. To generate disc degeneration at three different levels (L3-L4, L4-L5, or L5-S1), the material properties of the ground matrix of the annulus and bulk modulus of the nucleus were reduced. The finite element method combined with an optimization technique was applied to calculate the muscle forces. Minimization of deviations in the averaged tensile stress in the annulus fibres at the outermost layer in the five discs was selected for muscle force calculations. The results indicated that the disc degeneration noticeably increased the activation of the superficial muscle (IT and R) even though there was no clear change in the longissimus thoracis. Unlike some of the superficial muscles, activation in the deep muscles (multifidus (ML, MS, MT), LL and Q) was decreased. The change in TMR pattern generated an intervertebral disc angle difference and nucleus pressure increased in the upper level. These differences are expected to be functional in that they reduce the stress at the degenerated disc by changing the muscle activation, which slows down the progress of disc degeneration.

  9. Heme oxygenase-1 modulates degeneration of the intervertebral disc after puncture in Bach 1 deficient mice.

    PubMed

    Ohta, Ryo; Tanaka, Nobuhiro; Nakanishi, Kazuyoshi; Kamei, Naosuke; Nakamae, Toshio; Izumi, Bunichiro; Fujioka, Yuki; Ochi, Mitsuo

    2012-09-01

    Intervertebral disc degeneration is considered to be a major feature of low back pain. Furthermore, oxidative stress has been shown to be an important factor in degenerative diseases such as osteoarthritis and is considered a cause of intervertebral disc degeneration. The purpose of this study was to clarify the correlation between oxidative stress and intervertebral disc degeneration using Broad complex-Tramtrack-Bric-a-brac and cap'n'collar homology 1 deficient (Bach 1-/-) mice which highly express heme oxygenase-1 (HO-1). HO-1 protects cells from oxidative stress. Caudal discs of 12-week-old and 1-year-old mice were evaluated as age-related models. Each group and period, 5 mice (a total of 20 mice, a total of 20 discs) were evaluated as age-related model. C9-C10 caudal discs in 12-week-old Bach 1-/- and wild-type mice were punctured using a 29-gauge needle as annulus puncture model. Each group and period, 5 mice (a total of 60 mice, a total of 60 discs) were evaluated. The progress of disc degeneration was evaluated at pre-puncture, 1, 2, 4, 8 and 12 weeks post-puncture. Radiographic, histologic and immunohistologic analysis were performed to compare between Bach 1-/- and wild-type mice. In the age-related model, there were no significant differences between Bach 1-/- and wild-type mice radiologically and histologically. However, in the annulus puncture model, histological scoring revealed significant difference at 8 and 12 weeks post-puncture. The number of HO-1 positive cells was significantly greater in Bach 1-/- mice at every period. The apoptosis rate was significantly lower at 1 and 2 weeks post-puncture in Bach 1-/- mice. Oxidative stress prevention may avoid the degenerative process of the intervertebral disc after puncture, reducing the number of apoptosis cells. High HO-1 expression may also inhibit oxidative stress and delay the process of intervertebral disc degeneration.

  10. Progranulin Knockout Accelerates Intervertebral Disc Degeneration in Aging Mice

    PubMed Central

    Zhao, Yun-peng; Tian, Qing-yun; Liu, Ben; Cuellar, Jason; Richbourgh, Brendon; Jia, Tang-hong; Liu, Chuan-ju

    2015-01-01

    Intervertebral disc (IVD) degeneration is a common degenerative disease, yet much is unknown about the mechanisms during its pathogenesis. Herein we investigated whether progranulin (PGRN), a chondroprotective growth factor, is associated with IVD degeneration. PGRN was detectable in both human and murine IVD. The levels of PGRN were upregulated in murine IVD tissue during aging process. Loss of PGRN resulted in an early onset of degenerative changes in the IVD tissue and altered expressions of the degeneration-associated molecules in the mouse IVD tissue. Moreover, PGRN knockout mice exhibited accelerated IVD matrix degeneration, abnormal bone formation and exaggerated bone resorption in vertebra with aging. The acceleration of IVD degeneration observed in PGRN null mice was probably due to the enhanced activation of NF-κB signaling and β-catenin signaling. Taken together, PGRN may play a critical role in homeostasis of IVD, and may serve as a potential molecular target for prevention and treatment of disc degenerative diseases. PMID:25777988

  11. Protective effects of cannabidiol on lesion-induced intervertebral disc degeneration.

    PubMed

    Silveira, João W; Issy, Ana Carolina; Castania, Vitor A; Salmon, Carlos E G; Nogueira-Barbosa, Marcello H; Guimarães, Francisco S; Defino, Helton L A; Del Bel, Elaine

    2014-01-01

    Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content. Cannabidiol is the main non-psychotropic component of the Cannabis sativa with protective and anti-inflammatory properties. However, possible therapeutic effects of cannabidiol on intervertebral disc degeneration have not been investigated yet. The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI) and histological analyses. Disc injury was induced in the tail of male Wistar rats via a single needle puncture. The discs selected for injury were punctured percutaneously using a 21-gauge needle. MRI and histological evaluation were employed to assess the results. The effects of intradiscal injection of cannabidiol (30, 60 or 120 nmol) injected immediately after lesion were analyzed acutely (2 days) by MRI. The experimental group that received cannabidiol 120 nmol was resubmitted to MRI examination and then to histological analyses 15 days after lesion/cannabidiol injection. The needle puncture produced a significant disc injury detected both by MRI and histological analyses. Cannabidiol significantly attenuated the effects of disc injury induced by the needle puncture. Considering that cannabidiol presents an extremely safe profile and is currently being used clinically, these results suggest that this compound could be useful in the treatment of intervertebral disc degeneration.

  12. Protective Effects of Cannabidiol on Lesion-Induced Intervertebral Disc Degeneration

    PubMed Central

    Silveira, João W.; Issy, Ana Carolina; Castania, Vitor A.; Salmon, Carlos E. G.; Nogueira-Barbosa, Marcello H.; Guimarães, Francisco S.; Defino, Helton L. A.; Bel, Elaine Del

    2014-01-01

    Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content. Cannabidiol is the main non-psychotropic component of the Cannabis sativa with protective and anti-inflammatory properties. However, possible therapeutic effects of cannabidiol on intervertebral disc degeneration have not been investigated yet. The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI) and histological analyses. Disc injury was induced in the tail of male Wistar rats via a single needle puncture. The discs selected for injury were punctured percutaneously using a 21-gauge needle. MRI and histological evaluation were employed to assess the results. The effects of intradiscal injection of cannabidiol (30, 60 or 120 nmol) injected immediately after lesion were analyzed acutely (2 days) by MRI. The experimental group that received cannabidiol 120 nmol was resubmitted to MRI examination and then to histological analyses 15 days after lesion/cannabidiol injection. The needle puncture produced a significant disc injury detected both by MRI and histological analyses. Cannabidiol significantly attenuated the effects of disc injury induced by the needle puncture. Considering that cannabidiol presents an extremely safe profile and is currently being used clinically, these results suggest that this compound could be useful in the treatment of intervertebral disc degeneration. PMID:25517414

  13. Rheology of intervertebral disc: an ex vivo study on the effect of loading history, loading magnitude, fatigue loading, and disc degeneration.

    PubMed

    Kuo, Ya-Wen; Wang, Jaw-Lin

    2010-07-15

    An ex vivo biomechanical study on the rheological properties of healthy porcine and degenerated human intervertebral disc. To quantify the effect of loading history, loading magnitude, fatigue loading, and degeneration on disc rheology. Disc rheological parameters, i.e., the aggregate modulus (HA) and hydraulic permeability (k) regulate the mechanical and biologic function of disc. The knowledge of effects of loading condition and degeneration on disc rheology can be beneficial for the design of new disc/nucleus implants or therapy. The following 4 phases of experiments were conducted to find the changes of disc rheological properties: (1) Effect of loading history during 1-hour creep (640 N) and relaxation (20% strain) test. (2) Effect of loading magnitude (420 N vs. 640 N) during the creep test. (3) Effect of fatigue loading (420 N, 5 Hz for 0.5, 1, and 2 hours) on the creep loading behavior. (4) Difference of healthy porcine and degenerated human discs during creep loading. The experimental data were fitted with linear biphasic model. The aggregate modulus increased but hydraulic permeability decreased during creep loading. The aggregate modulus decreased but the hydraulic permeability did not change significantly during relaxation loading. The higher creep loading increased the aggregate modulus but decreased the hydraulic permeability. The fatigue loading did not change the aggregate modulus significantly, but decreased hydraulic permeability. Comparing the degenerated human disc to the healthy porcine disc, the aggregate modulus was higher but the hydraulic permeability was lower. The external loading and degeneration induce disc structural changes, e.g., the disc water content and interstitial matrix porosity, hence affect the disc rheological properties. The increase of aggregate modulus may be due to the reduction of disc hydration level, whereas the decrease of hydraulic permeability may be because of the shrinkage of disc matrix pores.

  14. Disc in Flames: Roles of TNF-α and IL-1β in Intervertebral Disc Degeneration

    PubMed Central

    Johnson, Zariel I.; Schoepflin, Zachary R.; Choi, Hyowon; Shapiro, Irving M.; Risbud, Makarand V.

    2016-01-01

    The intervertebral disc is an important mechanical structure that allows range of motion of the spinal column. Degeneration of the intervertebral disc, incited by aging, traumatic insult, genetic predisposition, or other factors, is often defined by functional and structural changes in the tissue, including excessive breakdown of the extracellular matrix, increased disc cell senescence and death, and compromised biomechanical function of the tissue. Intervertebral disc degeneration is strongly correlated with low back pain, which is a highly prevalent and costly condition, significantly contributing to loss in productivity and health care costs. Disc degeneration is a chronic, progressive condition, and current therapies are limited and often focused on symptomatic pain relief rather than curtailing the progression of the disease. Inflammatory processes, exacerbated by cytokines TNF-α and IL-1β are believed to be key mediators of disc degeneration and low back pain. In this review, we describe the contributions of TNF-α and IL-1β to changes seen during disc degeneration at the cellular and tissue level, new evidence suggesting a link between infection of the spine and low back pain, and the emerging therapeutic modalities aimed at combating these processes. PMID:26388614

  15. Lumbar Disc Degenerative Disease: Disc Degeneration Symptoms and Magnetic Resonance Image Findings

    PubMed Central

    Saleem, Shafaq; Rehmani, Muhammad Asim Khan; Raees, Aisha; Alvi, Arsalan Ahmad; Ashraf, Junaid

    2013-01-01

    Study Design Cross sectional and observational. Purpose To evaluate the different aspects of lumbar disc degenerative disc disease and relate them with magnetic resonance image (MRI) findings and symptoms. Overview of Literature Lumbar disc degenerative disease has now been proven as the most common cause of low back pain throughout the world. It may present as disc herniation, lumbar spinal stenosis, facet joint arthropathy or any combination. Presenting symptoms of lumbar disc degeneration are lower back pain and sciatica which may be aggravated by standing, walking, bending, straining and coughing. Methods This study was conducted from January 2012 to June 2012. Study was conducted on the diagnosed patients of lumbar disc degeneration. Diagnostic criteria were based upon abnormal findings in MRI. Patients with prior back surgery, spine fractures, sacroiliac arthritis, metabolic bone disease, spinal infection, rheumatoid arthritis, active malignancy, and pregnancy were excluded. Results During the targeted months, 163 patients of lumbar disc degeneration with mean age of 43.92±11.76 years, came into Neurosurgery department. Disc degeneration was most commonly present at the level of L4/L5 105 (64.4%).Commonest types of disc degeneration were disc herniation 109 (66.9%) and lumbar spinal stenosis 37 (22.7%). Spondylolisthesis was commonly present at L5/S1 10 (6.1%) and associated mostly with lumbar spinal stenosis 7 (18.9%). Conclusions Results reported the frequent occurrence of lumbar disc degenerative disease in advance age. Research efforts should endeavor to reduce risk factors and improve the quality of life. PMID:24353850

  16. 1980 Volvo award in basic science. Proteoglycans in experimental intervertebral disc degeneration.

    PubMed

    Lipson, S J; Muir, H

    1981-01-01

    An animal model of intervertebral disc degeneration induced surgically by ventral nuclear herniation in the rabbit produces morphologic changes of disc degeneration. Histologic characteristics and proteoglycan changes have been studied at various times after herniation. After injury, there was metaplasia into fibrocartilage originating from the cells along the margins of the annular wound, with proliferation of cells changing almost the entire disc space into fibrocartilage. A vertebral osteophyte occurred through an endochondral ossification sequence. Aggregating proteoglycans had two periods of repletion in the early course of degeneration. The water content of the disc was rapidly but only transiently restored in the first two days after herniation, whilst the changes in the total proteoglycan content of the disc paralleled these changes. Hyaluronic acid content decreased rapidly after herniation, but the size of the proteoglycan monomers did not change with degeneration. It is suggested that loss of confined fluid mechanics signals an abortive repair attempt rather than that of biochemical changes in proteoglycans initiate disc degeneration.

  17. Biological treatment strategies for disc degeneration: potentials and shortcomings

    PubMed Central

    Nerlich, Andreas G.; Boos, Norbert

    2006-01-01

    Recent advances in molecular biology, cell biology and material sciences have opened a new emerging field of techniques for the treatment of musculoskeletal disorders. These new treatment modalities aim for biological repair of the affected tissues by introducing cell-based tissue replacements, genetic modifications of resident cells or a combination thereof. So far, these techniques have been successfully applied to various tissues such as bone and cartilage. However, application of these treatment modalities to cure intervertebral disc degeneration is in its very early stages and mostly limited to experimental studies in vitro or in animal studies. We will discuss the potential and possible shortcomings of current approaches to biologically cure disc degeneration by gene therapy or tissue engineering. Despite the increasing number of studies examining the therapeutic potential of biological treatment strategies, a practicable solution to routinely cure disc degeneration might not be available in the near future. However, knowledge gained from these attempts might be applied in a foreseeable future to cure the low back pain that often accompanies disc degeneration and therefore be beneficial for the patient. PMID:16983559

  18. The effect of kyphoscoliosis on intervertebral disc degeneration in dogs.

    PubMed

    Faller, Kiterie; Penderis, Jacques; Stalin, Catherine; Guevar, Julien; Yeamans, Carmen; Gutierrez-Quintana, Rodrigo

    2014-06-01

    In people, abnormalities in vertebral column conformation, such as kyphoscoliosis, induce degenerative changes in adjacent intervertebral disc (IVD) structure and composition. It was hypothesised that canine IVDs adjacent to a vertebral malformation undergo early degeneration. In a blinded retrospective study, thoracic IVD degeneration was evaluated in 14 dogs on magnetic resonance images using Pfirrmann's grade. IVDs adjacent to a vertebral malformation had higher grades of degeneration than non-adjacent IVDs (P < 0.0001). There was an age-dependency, with dogs between 1 and 4 years showing higher grade of degeneration in adjacent than non-adjacent IVDs (P < 0.0001). Conversely, in older dogs, all IVDs - including the non-adjacents - showed degenerative signs, possibly due to normal aging. These results suggest that congenital vertebral malformation results in early degeneration of adjacent IVDs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. 3D finite element analysis of nutrient distributions and cell viability in the intervertebral disc: effects of deformation and degeneration.

    PubMed

    Jackson, Alicia R; Huang, Chun-Yuh C; Brown, Mark D; Gu, Wei Yong

    2011-09-01

    The intervertebral disc (IVD) receives important nutrients, such as glucose, from surrounding blood vessels. Poor nutritional supply is believed to play a key role in disc degeneration. Several investigators have presented finite element models of the IVD to investigate disc nutrition; however, none has predicted nutrient levels and cell viability in the disc with a realistic 3D geometry and tissue properties coupled to mechanical deformation. Understanding how degeneration and loading affect nutrition and cell viability is necessary for elucidating the mechanisms of disc degeneration and low back pain. The objective of this study was to analyze the effects of disc degeneration and static deformation on glucose distributions and cell viability in the IVD using finite element analysis. A realistic 3D finite element model of the IVD was developed based on mechano-electrochemical mixture theory. In the model, the cellular metabolic activities and viability were related to nutrient concentrations, and transport properties of nutrients were dependent on tissue deformation. The effects of disc degeneration and mechanical compression on glucose concentrations and cell density distributions in the IVD were investigated. To examine effects of disc degeneration, tissue properties were altered to reflect those of degenerated tissue, including reduced water content, fixed charge density, height, and endplate permeability. Two mechanical loading conditions were also investigated: a reference (undeformed) case and a 10% static deformation case. In general, nutrient levels decreased moving away from the nutritional supply at the disc periphery. Minimum glucose levels were at the interface between the nucleus and annulus regions of the disc. Deformation caused a 6.2% decrease in the minimum glucose concentration in the normal IVD, while degeneration resulted in an 80% decrease. Although cell density was not affected in the undeformed normal disc, there was a decrease in cell

  20. Inhibitory Effects of Platelet-Rich Plasma on Intervertebral Disc Degeneration: A Preclinical Study in a Rabbit Model

    PubMed Central

    Gui, Keke; Ren, Weimin; Yu, Yonglin; Li, Xin; Dong, Jiachun; Yin, Wangping

    2015-01-01

    Background Platelet-rich plasma (PRP) contains multiple growth hormones that may stimulate tissue repair. This study aimed to assess the effects of PRP in a rabbit model of IDD (annulus fibrosus puncture). Material/Methods Thirty-six adult New Zealand white rabbits were randomly divided into 3 groups: 0.1 mL PRP (group A), 0.1 mL phosphate-buffered saline (group B), and control (group C) (n=12/group). Annulus fibrosus puncture was performed to establish L4/5 and L5/6 IDD models. Two and 4 weeks later, 6 rabbits from each group were given an IVD injection at L4/5 and L5/6. Two or 4 weeks after injection, rabbits were scanned with X-ray and MRI before being sacrificed. IVDs were collected for hematoxylin and eosin, Masson’s trichrome, and Safranin O staining, and type II collagen immunohistochemistry. Results Over time, IVD height and disc imaging signal intensity decreased gradually in groups B and C, but only slightly in group A (baseline: 100% for all groups; A: 95.9±4.2% at 4 weeks, 90.1±8.4 at 6 weeks; B: 75.3±5.7% at 4 weeks, 70.8±6.4% at 6 weeks; C: 74.7±5.5% at 4 weeks, 69.9±6.2% at 6 weeks; all P<0.001, P<0.01 between A vs. B and C). Degenerative histological changes in IVDs in groups B and C were more severe compared with group A. Conclusions Platelet-rich plasma interventions can effectively attenuate the IDD process in rabbits. PMID:25965093

  1. Histological Identification of Propionibacterium acnes in Nonpyogenic Degenerated Intervertebral Discs

    PubMed Central

    Yuan, Ye; Zhou, Zezhu; Jiao, Yucheng; Zheng, Yuehuan; Lin, Yazhou; Xiao, Jiaqi

    2017-01-01

    Purpose. Low-virulence anaerobic bacteria, especially the Propionibacterium acnes (P. acnes), have been thought to be a new pathogeny for a series of disc diseases. However, until now, there has been no histological evidence to confirm this link. The purpose of this study was to confirm the presence of P. acnes in nonpyogenic intervertebral discs via histological observation. Method. Degenerated intervertebral discs were harvested from 76 patients with low back pain and/or sciatica but without any symptoms of discitis or spondylodiscitis. The samples were cultured under anaerobic conditions and then examined using 16S rDNA PCR to screen for P. acnes. Samples found to be positive for P. acnes were stained with hematoxylin-eosin (HE) and modified Brown-Brenn staining and observed under a microscope. Results. Here, 16 intervertebral discs were found to be positive for P. acnes via 16S rDNA PCR and the prevalence was 21.05% (16/76). Among them, 7 samples had visible microbes stained with HE and modified Brown-Brenn staining. Morphological examination showed the bacteria to be Gram-positive and rod-shaped, so they were considered P. acnes. Conclusion. P. acnes is capable of colonizing some degenerated intervertebral discs without causing discitis, and its presence could be further confirmed by histological evidence. Targeting these bacteria may be a promising therapy method for some disc diseases. PMID:28401158

  2. Angiogenesis in the degeneration of the lumbar intervertebral disc

    PubMed Central

    David, Gh; Iencean, SM; Mohan, A

    2010-01-01

    The goal of the study is to show the histological and biochemical changes that indicate the angiogenesis of the intervertebral disc in lumbar intervertebral disc hernia and the existence of epidemiological correlations between these changes and the risk factors of lumbar intervertebral disc hernia, as well as the patient's quality of life (QOL). We have studied 50 patients aged between 18 and 73 years old, who have undergone lumbar intervertebral disc hernia surgery, making fibroblast growth factor and vascular endothelial growth factor level measurements, as elements in the process of appreciating the disc angiogenesis. Also, pre–surgery and post–surgery QOL has been measured, as well as the intensity of the pain syndrome. We have identified factors capable of stimulating vascular endothelial growth (VEGF, FGF–2) for the examined disc material, but histological examination did not show angiogenesis. The process of angiogenesis at the degenerated intervertebral disc level affects the patient's quality of life both pre and postoperatively, and may be a predictive factor for the post–operative results. Patients can prevent the appearance of angiogenesis type degenerative processes of the intervertebral disc by avoiding angiogenesis correlated factors (weight control, physical effort, and smoking). PMID:20968201

  3. Morphologic features of spontaneous annular tears and disc degeneration in the aging sand rat (Psammomys obesus obesus).

    PubMed

    Gruber, H E; Hanley, E N

    2017-08-11

    The sand rat, a member of the gerbil family, is a valuable small animal model in which intervertebral disc degeneration occurs spontaneously as the animal ages. Radiographic features of cervical and lumbar degeneration resemble those in human spines. We conducted a retrospective analysis of spines of 140 animals 3-41 months old focusing specifically on the presence of annular tears that are not visible by radiography and have not been described previously in the sand rat disc. During degeneration of the nucleus pulposus, notochordal cell death occurs and granular material, which stains with Alcian blue for proteoglycans, accumulates. Lamellar architecture also deteriorates and annular tears occur that are morphologically similar to the concentric, radiating and transdiscal annular tears in human discs. These tears contain granular material that provides a "marker" that can be used to distinguish the annular tears from artefactual separations during sectioning. We observed lamellar degeneration and separation in the annulus fibrosus at 4 months with associated tears that contained granular material in the nucleus. Tears that contained granular material and displacement of the degenerating nucleus were common in cervical and lumbar discs of animals older than 9 months; some specimens showed tears at 4 and 5 months. With advanced degeneration, granular globules were displaced dorsally adjacent to and into the spinal cord area and also ventrally into regions where osteophytes formed. We present morphologic data that expand the utility of this rodent model of spontaneous age-related disc degeneration and provide novel information on annular tears and disc degeneration.

  4. The relationship between quantitative measures of disc height and disc signal intensity with Pfirrmann score of disc degeneration.

    PubMed

    Salamat, Sara; Hutchings, John; Kwong, Clemens; Magnussen, John; Hancock, Mark J

    2016-01-01

    To assess the relationship between quantitative measures of disc height and signal intensity with the Pfirrmann disc degeneration scoring system and to test the inter-rater reliability of the quantitative measures. Participants were 76 people who had recently recovered from their last episode of acute low back pain and underwent MRI scan on a single 3T machine. At all 380 lumbar discs, quantitative measures of disc height and signal intensity were made by 2 independent raters and compared to Pfirrmann scores from a single radiologist. For quantitative measures of disc height and signal intensity a "raw" score and 2 adjusted ratios were calculated and the relationship with Pfirrmann scores was assessed. The inter-tester reliability of quantitative measures was also investigated. There was a strong linear relationship between quantitative disc signal intensity and Pfirrmann scores for grades 1-4, but not for grades 4 and 5. For disc height only, Pfirrmann grade 5 had significantly reduced disc height compared to all other grades. Results were similar regardless of whether raw or adjusted scores were used. Inter-rater reliability for the quantitative measures was excellent (ICC > 0.97). Quantitative measures of disc signal intensity were strongly related to Pfirrmann scores from grade 1 to 4; however disc height only differentiated between grade 4 and 5 Pfirrmann scores. Using adjusted ratios for quantitative measures of disc height or signal intensity did not significantly alter the relationship with Pfirrmann scores.

  5. ROS: Crucial Intermediators in the Pathogenesis of Intervertebral Disc Degeneration

    PubMed Central

    Yang, Minghui; Lan, Minghong; Liu, Chang; Zhang, Yang; Huang, Bo

    2017-01-01

    Excessive reactive oxygen species (ROS) generation in degenerative intervertebral disc (IVD) indicates the contribution of oxidative stress to IVD degeneration (IDD), giving a novel insight into the pathogenesis of IDD. ROS are crucial intermediators in the signaling network of disc cells. They regulate the matrix metabolism, proinflammatory phenotype, apoptosis, autophagy, and senescence of disc cells. Oxidative stress not only reinforces matrix degradation and inflammation, but also promotes the decrease in the number of viable and functional cells in the microenvironment of IVDs. Moreover, ROS modify matrix proteins in IVDs to cause oxidative damage of disc extracellular matrix, impairing the mechanical function of IVDs. Consequently, the progression of IDD is accelerated. Therefore, a therapeutic strategy targeting oxidative stress would provide a novel perspective for IDD treatment. Various antioxidants have been proposed as effective drugs for IDD treatment. Antioxidant supplementation suppresses ROS production in disc cells to promote the matrix synthesis of disc cells and to prevent disc cells from death and senescence in vitro. However, there is not enough in vivo evidence to support the efficiency of antioxidant supplementation to retard the process of IDD. Further investigations based on in vivo and clinical studies will be required to develop effective antioxidative therapies for IDD. PMID:28392887

  6. Role of Cytokines in Intervertebral Disc Degeneration: Pain and Disc-content

    PubMed Central

    Risbud, Makarand V.; Shapiro, Irving. M

    2014-01-01

    Degeneration of the intervertebral disc is the major contributor to back/neck and radicular pain. It is characterized by an elevation in levels of the inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1 α/β, IL-6 and IL-17 secreted by the disc cells themselves; these cytokines promote matrix degradation, chemokine production and changes in cell phenotype. The resulting imbalance between catabolic and anabolic responses leads to degeneration, as well as herniation and radicular pain. Release of chemokines from degenerating discs promote infiltration and activation of T and B cells, macrophages, neutrophils, and mast cells further amplifying the inflammatory cascade. Immunocyte migration into the disc is accompanied by the appearance of microvasculature and nerve fibers arising from the dorsal root ganglion (DRG). In this inflammatory milieu, neurogenic factors in particular nerve growth factor (NGF) and brain-derive neurotrophic factor (BDNF) generated by disc and immune cells induce expression of pain associated cation channels in DRGs. Depolarization of these channels is likely to promote discogenic and radicular pain and reinforce the cytokine-mediated degenerative cascade. Taken together, the enhanced understanding of the contribution of cytokines and immune cells to catabolic and nociceptive processes provide new targets for treating symptomatic disc disease. PMID:24166242

  7. Effects of Tobacco Smoking on the Degeneration of the Intervertebral Disc: A Finite Element Study.

    PubMed

    Elmasry, Shady; Asfour, Shihab; de Rivero Vaccari, Juan Pablo; Travascio, Francesco

    2015-01-01

    Tobacco smoking is associated with numerous pathological conditions. Compelling experimental evidence associates smoking to the degeneration of the intervertebral disc (IVD). In particular, it has been shown that nicotine down-regulates both the proliferation rate and glycosaminoglycan (GAG) biosynthesis of disc cells. Moreover, tobacco smoking causes the constriction of the vascular network surrounding the IVD, thus reducing the exchange of nutrients and anabolic agents from the blood vessels to the disc. It has been hypothesized that both nicotine presence in the IVD and the reduced solute exchange are responsible for the degeneration of the disc due to tobacco smoking, but their effects on tissue homeostasis have never been quantified. In this study, a previously presented computational model describing the homeostasis of the IVD was deployed to investigate the effects of impaired solute supply and nicotine-mediated down-regulation of cell proliferation and biosynthetic activity on the health of the disc. We found that the nicotine-mediated down-regulation of cell anabolism mostly affected the GAG concentration at the cartilage endplate, reducing it up to 65% of the value attained in normal physiological conditions. In contrast, the reduction of solutes exchange between blood vessels and disc tissue mostly affected the nucleus pulposus, whose cell density and GAG levels were reduced up to 50% of their normal physiological levels. The effectiveness of quitting smoking on the regeneration of a degenerated IVD was also investigated, and showed to have limited benefit on the health of the disc. A cell-based therapy in conjunction with smoke cessation provided significant improvements in disc health, suggesting that, besides quitting smoking, additional treatments should be implemented in the attempt to recover the health of an IVD degenerated by tobacco smoking.

  8. Effects of Tobacco Smoking on the Degeneration of the Intervertebral Disc: A Finite Element Study

    PubMed Central

    Elmasry, Shady; Asfour, Shihab; de Rivero Vaccari, Juan Pablo; Travascio, Francesco

    2015-01-01

    Tobacco smoking is associated with numerous pathological conditions. Compelling experimental evidence associates smoking to the degeneration of the intervertebral disc (IVD). In particular, it has been shown that nicotine down-regulates both the proliferation rate and glycosaminoglycan (GAG) biosynthesis of disc cells. Moreover, tobacco smoking causes the constriction of the vascular network surrounding the IVD, thus reducing the exchange of nutrients and anabolic agents from the blood vessels to the disc. It has been hypothesized that both nicotine presence in the IVD and the reduced solute exchange are responsible for the degeneration of the disc due to tobacco smoking, but their effects on tissue homeostasis have never been quantified. In this study, a previously presented computational model describing the homeostasis of the IVD was deployed to investigate the effects of impaired solute supply and nicotine-mediated down-regulation of cell proliferation and biosynthetic activity on the health of the disc. We found that the nicotine-mediated down-regulation of cell anabolism mostly affected the GAG concentration at the cartilage endplate, reducing it up to 65% of the value attained in normal physiological conditions. In contrast, the reduction of solutes exchange between blood vessels and disc tissue mostly affected the nucleus pulposus, whose cell density and GAG levels were reduced up to 50% of their normal physiological levels. The effectiveness of quitting smoking on the regeneration of a degenerated IVD was also investigated, and showed to have limited benefit on the health of the disc. A cell-based therapy in conjunction with smoke cessation provided significant improvements in disc health, suggesting that, besides quitting smoking, additional treatments should be implemented in the attempt to recover the health of an IVD degenerated by tobacco smoking. PMID:26301590

  9. Menopause causes vertebral endplate degeneration and decrease in nutrient diffusion to the intervertebral discs.

    PubMed

    Wang, Yi-Xiang J; Griffith, James F

    2011-07-01

    The vasculature in the outer annulus supplies only the periphery of the disc so that nutrition to the bulk of the disc, including all the inner annulus and nucleus pulposus, is derived from the vertebral epiphyseal end arteries where nutrients diffuse across the cartilaginous endplate to reach the disc. In this regard the vertebral endplate plays an important role in disc nutrition. Compromise of diffusion of nutrients to the disc cells may play a large part in the progression or even initiation of disc degeneration. Increasing evidence suggests that estrogen deficiency also influence the severity of disc degeneration in post-menopausal females. Structural disorganization of the vertebral endplate occurs with disc degeneration, with the most common endplate changes observed clinically being Schmorl's node. Schmorl's node is more commonly seen in post-menopausal women than younger women. Osteosclerosis, osteonecrosis and fibrosis associated with Schmorl's nodes can impede nutrient diffusion into the disc as well as removal of metabolites from the disc. We hypothesize that menopause negatively affects vertebral endplate quality and induces endplate degeneration. This endplate degeneration decreases nutrients diffusion from vertebral body into discs, and also impedes removal of metabolites, leads to further disc degeneration. To confirm our hypothesis, a cross-sectional post-contrast MRI study can be performed in pre-menopausal and post-menopausal women. If the hypothesis is confirmed, then low dose hormone replacement treatment may retard disc degeneration in post menopausal women and thereby limit the consequences associated with disc degeneration such as low back pain.

  10. Systemic blood plasma CCL5 and CXCL6: Potential biomarkers for human lumbar disc degeneration.

    PubMed

    Grad, S; Bow, C; Karppinen, J; Luk, K D; Cheung, K M; Alini, M; Samartzis, D

    2016-01-05

    Lumbar disc degeneration severity on magnetic resonance imaging (MRI) is associated with low back pain. Pro-inflammatory chemokines CCL5 and CXCL6 are released by induced degenerative discs, and CCL5 has been associated with discogenic back pain. A case-control study was performed, based on the Hong Kong Disc Degeneration Population-Based Cohort of Southern Chinese, to investigate if systemic levels of CCL5 and CXCL6 were elevated in subjects with disc degeneration compared to non-degenerated individuals. Eighty subjects were selected, 40 with no disc degeneration (control group; DDD score 0) and 40 with moderate/severe disc degeneration (disc degeneration group; DDD score ≥5) as noted on MRI. Subjects were matched for age, sex, body mass index and workload. Blood plasma samples were obtained from each individual, and levels of CCL5 and CXCL6 were measured. Secondary phenotypes of lumbar disc displacement and cervical disc changes were also assessed. CCL5 concentrations were significantly increased in the disc degeneration (mean: 19.8 ng/mL) compared to the control group (mean: 12.8 ng/mL) (p = 0.015). The degeneration group demonstrated higher levels of CXCL6 (mean: 56.9 pg/mL) compared to the control group (mean: 43.4 pg/mL) (p = 0.010). There was a trend towards elevated CCL5 levels with disc displacement in the degeneration group (p = 0.073). Cervical disc degeneration was not associated with elevated chemokine levels (p > 0.05). This is the first study to note that elevated systemic CCL5 and CXCL6 were associated with moderate/severe lumbar disc degeneration, further corroborating tissue studies of painful discs. These chemokines may be systemic biomarkers for the diagnosis and monitoring of disc degeneration.

  11. Stimulation of gene expression and loss of anular architecture caused by experimental disc degeneration--an in vivo animal study.

    PubMed

    Guehring, Thorsten; Omlor, Georg W; Lorenz, Helga; Bertram, Helge; Steck, Eric; Richter, Wiltrud; Carstens, Claus; Kroeber, Markus

    2005-11-15

    An external compression model was used to evaluate gene and protein expression in intervertebral discs with moderate disc degeneration. To determine messenger ribonucleic acid and protein expression levels of relevant disc components. An animal model of mechanically induced disc degeneration was developed and characterized histologically. However, little is known at the molecular level in moderate disc degeneration. There were 8 New Zealand white rabbits subjected to monosegmental posterior compression to induce moderate disc degeneration. Twelve animals served as controls or sham controls. Discs were analyzed using immunohistochemistry for collagen type 1 (COL1), COL2, aggrecan, and bone morphogenetic protein-2/4 (BMP-2/4). For gene analysis, conventional and quantitative polymerase chain reactions were used for COL1A2, COL2A1, aggrecan, BMP-2, biglycan, decorin, osteonectin, fibromodulin, fibronectin, matrix metalloproteinase-13 (MMP-13), and tissue inhibitor of MMP-1. Gene expression for nontreated, sham-treated, and compressed discs was quantified in relation to the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase. Immunohistochemistry of compressed discs showed a loss of anular architecture, and a significant reduction of BMP-2/4 and COL2 positive cells. Gene expression analysis showed a significant up-regulation of COL1A2, osteonectin, decorin, fibronectin, tissue inhibitor of MMP-1, BMP-2, and MMP-13 in compressed discs. Experimental moderate disc degeneration is characterized by a loss of BMP-2/4 and COL2 positive cells, although gene expression of disc constituents, catabolic enzymes, and growth factors is stimulated to reestablish disc integrity.

  12. The Effect of Single-Level Disc Degeneration on Dynamic Response of the Whole Lumbar Spine to Vertical Vibration.

    PubMed

    Guo, Li-Xin; Fan, Wei

    2017-09-01

    The objective of this study was to investigate the effect of single-level disc degeneration on dynamic response of the whole lumbar spine to vertical whole body vibration that is typically present when driving vehicles. Ligamentous finite element models of the lumbar L1-S1 motion segment in different grades of degeneration (healthy, mild, and moderate) at the L4-L5 level were developed with consideration of changing disc height and material properties of the nucleus pulpous. All models were loaded with a compressive follower preload of 400 N and a sinusoidal vertical vibration load of ±40 N. After transient dynamic analyses, computational results for the 3 models in terms of disc bulge, von-Mises stress in annulus ground substance, and nucleus pressure were plotted as a function of time and compared. All the predicted results showed a cyclic response with time. At the degenerated L4-L5 disc level, as degeneration progressed, maximum value of the predicted response showed a decrease in disc bulge and von-Mises stress in annulus ground substance but a slight increase in nucleus pressure, and their vibration amplitudes were all decreased. At the adjacent levels of the degenerated disc, there was a slight decrease in maximum value and vibration amplitude of these predicted responses with the degeneration. The results indicated that single-level disc degeneration can alter vibration characteristics of the whole lumbar spine especially for the degenerated disc level, and increasing the degeneration did not deteriorate the effect of vertical vibration on the spine. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Blocking the Function of Inflammatory Cytokines and Mediators by Using IL-10 and TGF-β: A Potential Biological Immunotherapy for Intervertebral Disc Degeneration in a Beagle Model

    PubMed Central

    Li, Wei; Liu, Tianyi; Wu, Liangliang; Chen, Chun; Jia, Zhiwei; Bai, Xuedong; Ruan, Dike

    2014-01-01

    The debilitating effects of lower back pain are a major health issue worldwide. A variety of factors contribute to this, and oftentimes intervertebral disk degeneration (IDD) is an underlying cause of this disorder. Inflammation contributes to IDD, and inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, play key roles in the pathology of IDD. Therefore, the development of treatments that inhibit the expression and/or effects of TNF-α and IL-1β in IDD patients should be a promising therapeutic approach to consider. This study characterized the potential to suppress inflammatory cytokine production in degenerative intervertebral disc (NP) cells by treatment with IL-10 and TGF-β in a canine model of IDD. IDD was induced surgically in six male beagles, and degenerative NP cells were isolated and cultured for in vitro studies on cytokine production. Cultured degenerative NP cells were divided into four experimental treatment groups: untreated control, IL-10-treated, TGF-β-treated, and IL-10- plus TGF-β-treated cells. Cultured normal NP cells served as a control group. TNF-α expression was evaluated by fluorescence activated cell sorting (FACS) analysis and enzyme-linked immunosorbent assay (ELISA); moreover, ELISA and real-time PCR were also performed to evaluate the effect of IL-10 and TGF-β on NP cell cytokine expression in vitro. Our results demonstrated that IL-10 and TGF-β treatment suppressed the expression of IL-1β and TNF-α and inhibited the development of inflammatory responses. These data suggest that IL-10 and TGF-β should be evaluated as therapeutic approaches for the treatment of lower back pain mediated by IDD. PMID:25264742

  14. Mitochondrial-derived reactive oxygen species (ROS) play a causal role in aging-related intervertebral disc degeneration.

    PubMed

    Nasto, Luigi A; Robinson, Andria R; Ngo, Kevin; Clauson, Cheryl L; Dong, Qing; St Croix, Claudette; Sowa, Gwendolyn; Pola, Enrico; Robbins, Paul D; Kang, James; Niedernhofer, Laura J; Wipf, Peter; Vo, Nam V

    2013-07-01

    Oxidative damage is a well-established driver of aging. Evidence of oxidative stress exists in aged and degenerated discs, but it is unclear how it affects disc metabolism. In this study, we first determined whether oxidative stress negatively impacts disc matrix metabolism using disc organotypic and cell cultures. Mouse disc organotypic culture grown at atmospheric oxygen (20% O(2)) exhibited perturbed disc matrix homeostasis, including reduced proteoglycan synthesis and enhanced expression of matrix metalloproteinases, compared to discs grown at low oxygen levels (5% O(2)). Human disc cells grown at 20% O(2) showed increased levels of mitochondrial-derived superoxide anions and perturbed matrix homeostasis. Treatment of disc cells with the mitochondria-targeted reactive oxygen species (ROS) scavenger XJB-5-131 blunted the adverse effects caused by 20% O(2). Importantly, we demonstrated that treatment of accelerated aging Ercc1(-/Δ) mice, previously established to be a useful in vivo model to study age-related intervertebral disc degeneration (IDD), also resulted in improved disc total glycosaminoglycan content and proteoglycan synthesis. This demonstrates that mitochondrial-derived ROS contributes to age-associated IDD in Ercc1(-/Δ) mice. Collectively, these data provide strong experimental evidence that mitochondrial-derived ROS play a causal role in driving changes linked to aging-related IDD and a potentially important role for radical scavengers in preventing IDD.

  15. Feasibility of a stem cell therapy for intervertebral disc degeneration.

    PubMed

    Sobajima, Satoshi; Vadala, Gianluca; Shimer, Adam; Kim, Joseph S; Gilbertson, Lars G; Kang, James D

    2008-01-01

    Different strategies to supplement/replenish the disc cell population have been proposed. Recently, adult stem cells have shown promise as a cell source for a variety of tissue engineering and cell therapy applications. A stem cell can renew itself through cell division and can be induced to develop into many different specialized cell types. Moreover, stem cells have shown ability to migrate and engraft within various tissues, as well as to exert stimulatory effects on other cell types through various mechanisms (eg, paracrine effects, cell-cell interactions). These characteristics make stem cells worthy of investigation as a source of cells for intervertebral disc (IVD) tissue engineering and cell therapy. To determine feasibility of a stem cell therapy of IVD degeneration. In vitro studies of adult human cells to examine interactions between nucleus pulposus cells (NPCs) and mesenchymal stem cells (MSCs) at different ratios in 3-D pellet culture. In vivo studies of healthy adult rabbit discs injected with allogenic adult rabbit MSCs to examine stem cell survival and engraftment in living disc tissue. In vitro study: Human NPCs were cocultured with human MSCs in different ratios (75:25, 50:50, 25:75) for 2 weeks in pellet culture, for comparison with pure NPC (100:0) and pure MSC (0:100) pellet cultures. Proteoglycan synthesis rate and glycosaminoglycan (GAG) content were measured by radioactive sulfate incorporation and dimethylmethylene blue assay, respectively. In vivo study: MSCs were isolated from the bone marrow of a New Zealand White (NZW) rabbit, retrovirally transduced with the lacZ marker gene, and injected into the nucleus pulposi of the L2-3, L3-4, and L4-5 lumbar discs of 12 other NZW rabbits. Three rabbits each were sacrificed at 3, 6, 12, or 24 weeks after cell implantation, and X-Gal staining was done to assess survival and localization of MSCs in the disc tissues. In vitro study: the 75:25 and 50:50 NPC:MSC cocultures yielded the greatest

  16. Reconstitution of degenerated ovine lumbar discs by STRO-3-positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate.

    PubMed

    Oehme, David; Ghosh, Peter; Goldschlager, Tony; Itescu, Silviu; Shimon, Susan; Wu, Jiehua; McDonald, Courtney; Troupis, John M; Rosenfeld, Jeffrey V; Jenkin, Graham

    2016-05-01

    OBJECTIVE Disc degeneration and associated low-back pain are major causes of suffering and disability. The authors examined the potential of mesenchymal precursor cells (MPCs), when formulated with pentosan polysulfate (PPS), to ameliorate disc degeneration in an ovine model. METHODS Twenty-four sheep had annular incisions made at L2-3, L3-4, and L4-5 to induce degeneration. Twelve weeks after injury, the nucleus pulposus of a degenerated disc in each animal was injected with ProFreeze and PPS formulated with either a low dose (0.1 million MPCs) or a high dose (0.5 million MPCs) of cells. The 2 adjacent injured discs in each spine were either injected with PPS and ProFreeze (PPS control) or not injected (nil-injected control). The adjacent noninjured L1-2 and L5-6 discs served as noninjured control discs. Disc height indices (DHIs) were obtained at baseline, before injection, and at planned death. After necropsy, 24 weeks after injection, the spines were subjected to MRI and morphological, histological, and biochemical analyses. RESULTS Twelve weeks after the annular injury, all the injured discs exhibited a significant reduction in mean DHI (low-dose group 17.19%; high-dose group 18.01% [p < 0.01]). Twenty-four weeks after injections, the discs injected with the low-dose MPC+PPS formulation recovered disc height, and their mean DHI was significantly greater than the DHI of PPS- and nil-injected discs (p < 0.001). Although the mean Pfirrmann MRI disc degeneration score for the low-dose MPC+PPS-injected discs was lower than that for the nil- and PPS-injected discs, the differences were not significant. The disc morphology scores for the nil- and PPS-injected discs were significantly higher than the normal control disc scores (p < 0.005), whereas the low-dose MPC+PPS-injected disc scores were not significantly different from those of the normal controls. The mean glycosaminoglycan content of the nuclei pulposus of the low-dose MPC+PPS-injected discs was significantly

  17. Axial Creep Loading and Unloaded Recovery of the Human Intervertebral Disc and the Effect of Degeneration

    PubMed Central

    O'Connell, Grace D.; Jacobs, Nathan T.; Sen, Sounok; Vresilovic, Edward J.; Elliott, Dawn M.

    2011-01-01

    The intervertebral disc maintains a balance between externally applied loads and internal osmotic pressure. Fluid flow plays a key role in this process, causing fluctuations in disc hydration and height. The objectives of this study were to quantify and model the axial creep and recovery responses of nondegenerate and degenerate human lumbar discs. Two experiments were performed. First, a slow compressive ramp was applied to 2000 N, unloaded to allow recovery for up to 24 hours, and re-applied. The linear-region stiffness and disc height were within 5% of the initial condition for recovery times greater than 8 hours. In the second experiment, a 1000 N creep load was applied for four hours, unloaded recovery monitored for 24 hours, and the creep load repeated. A viscoelastic model comprised of a “fast” and “slow” exponential response was used to describe the creep and recovery, where the fast response is associated with flow in the nucleus pulposus (NP) and endplate, while the slow response is associated with the annulus fibrosus (AF). The study demonstrated that recovery is 3-4X slower than loading. The fast response was correlated with degeneration, suggesting larger changes in the NP with degeneration compared to the AF. However, the fast response comprised only 10-15% of the total equilibrium displacement, with the AF-dominated slow response comprising 40-70%. Finally, the physiological loads and deformations and their associated long equilibrium times confirm that diurnal loading does not represent “equilibrium” in the disc, but that over time the disc is in steady-state. PMID:21783103

  18. Clinical Impact of Sagittal Spinopelvic Parameters on Disc Degeneration in Young Adults

    PubMed Central

    Oh, Young-Min; Eun, Jong-Pil

    2015-01-01

    Abstract The sagittal balance plays an important role in the determination of shear and compressive forces applied on the anterior (vertebral bodies and intervertebral discs) and posterior (facet joints) elements of the lumbar vertebral column. Many studies have also examined the effect of structural changes in the disc on the biomechanical characteristics of the spinal segment. Nevertheless, the relationship between sagittal balance and the degree of disc degeneration has not been extensively explored. Thus, here we investigated the relationships between various sagittal spinopelvic parameters and the degree of disc degeneration in young adults. A total of 278 young adult male patients were included in this study (age range: 18–24 years old). Multiple sagittal spinopelvic parameters, including pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), sacral inclination (SI), lumbosacral angle (LSA), and sacral table angle (STA), were measured from standing lateral lumbosacral radiographs. The degree of intervertebral disc degeneration was classified using a modified Pfirrmann scale. To assess the pain intensity of each patient, the visual analogue scale (VAS) score for low back pain (LBP) was obtained from all the patients. Finally, the relationships between these spinopelvic parameters and the degree of disc degeneration in young adults were analyzed. Also, we performed multiple logistic regression study. Out of all the spinopelvic parameters measured in this study, a low STA and a low SI were the only significant risk factors that were associated with disc degeneration in young adults. It means that patients with disc degeneration tend to have more severe sacral kyphosis and vertical sacrum. We found that patients with disc degeneration showed a lower SI and lower STA compared with patients without disc degeneration in young adults. Therefore, we suggest that the patients with disc degeneration tend to have more vertical sacrum, more

  19. Clinical Impact of Sagittal Spinopelvic Parameters on Disc Degeneration in Young Adults.

    PubMed

    Oh, Young-Min; Eun, Jong-Pil

    2015-10-01

    The sagittal balance plays an important role in the determination of shear and compressive forces applied on the anterior (vertebral bodies and intervertebral discs) and posterior (facet joints) elements of the lumbar vertebral column. Many studies have also examined the effect of structural changes in the disc on the biomechanical characteristics of the spinal segment. Nevertheless, the relationship between sagittal balance and the degree of disc degeneration has not been extensively explored. Thus, here we investigated the relationships between various sagittal spinopelvic parameters and the degree of disc degeneration in young adults.A total of 278 young adult male patients were included in this study (age range: 18-24 years old). Multiple sagittal spinopelvic parameters, including pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), sacral inclination (SI), lumbosacral angle (LSA), and sacral table angle (STA), were measured from standing lateral lumbosacral radiographs. The degree of intervertebral disc degeneration was classified using a modified Pfirrmann scale. To assess the pain intensity of each patient, the visual analogue scale (VAS) score for low back pain (LBP) was obtained from all the patients. Finally, the relationships between these spinopelvic parameters and the degree of disc degeneration in young adults were analyzed. Also, we performed multiple logistic regression study.Out of all the spinopelvic parameters measured in this study, a low STA and a low SI were the only significant risk factors that were associated with disc degeneration in young adults. It means that patients with disc degeneration tend to have more severe sacral kyphosis and vertical sacrum.We found that patients with disc degeneration showed a lower SI and lower STA compared with patients without disc degeneration in young adults. Therefore, we suggest that the patients with disc degeneration tend to have more vertical sacrum, more sacral kyphosis

  20. Effect of nicotine on spinal disc cells: a cellular mechanism for disc degeneration.

    PubMed

    Akmal, Mohammed; Kesani, Anil; Anand, Bobby; Singh, Abhinav; Wiseman, Mike; Goodship, Allen

    2004-03-01

    Experimental investigation to determine the effect of nicotine on intervertebral spinal disc nucleus pulposus (NP) cells cultured in vitro. OBJECTIVES.: To evaluate the effects of nicotine on cell proliferation, extracellular matrix production, and viability of NP cells in three-dimensional alginate constructs cultured in vitro. Numerous studies confirm that smoking is a strong risk factor for back pain. The most widely accepted explanations for the association between smoking and disc degeneration is malnutrition of spinal disc cells by carboxy-hemoglobin-induced anoxia or vascular disease. Nicotine, a constituent of tobacco smoke, present in most body fluids of smokers is known to have detrimental effects on a variety of tissues. It may also be directly responsible for intervertebral disc (IVD) degeneration by causing cell damage in both the nucleus pulposus and anulus fibrosus. The effect of nicotine on IVD cells has not previously been investigated. Bovine chondrocytic intervertebral disc cells were isolated by sequential digestion of nucleus pulposus and seeded in 2% alginate. The constructs were cultured for 21 days either in growth medium containing freebase nicotine (Sigma) at concentrations found in the serum of smokers (25 nmol/L-300 nmol/L) or in standard nicotine free-medium as controls. Samples were collected at time points 3, 7, 14, and 21 days and a quantitative assay was performed for DNA, glycosaminoglycans (GAG), and hydroxyproline. Samples were also processed for qualitative histologic analysis including immunolocalization of collagen types I and II. There was both a dose- and time-dependent response to nicotine, with constructs cultured in low-nicotine concentration media demonstrating an early increase in DNA, GAG, and collagen content, while constructs cultured in high nicotine concentration media demonstrated a late decrease in these parameters. At 25 nmol/L dose of nicotine, there was a significant increase (P < 0.05) in the above parameters

  1. Landscape of RNAs in human lumbar disc degeneration

    PubMed Central

    Pei, Yan-Jun; Wu, Zhi-Gang; Yu, Yang; Yang, Yong-Feng; Liu, Xu; Che, Lu; Ma, Chi-Jiao; Xie, Yan-Ke; Hu, Qing-Jie; Wan, Zhong-Yuan; Wang, Hai-Qiang

    2016-01-01

    Accumulating evidence indicates noncoding RNAs (ncRNAs) fine-tune gene expression with mysterious machinery. We conducted a combination of mRNA, miRNA, circRNA, LncRNA microarray analyses on 10 adults' lumbar discs. Moreover, we performed additional global exploration on RNA interacting machinery in terms of in silico computational pipeline. Here we show the landscape of RNAs in human lumbar discs. In general, the RNA-abundant landscape comprises 14,635 mRNAs (37.93%), 2,059 miRNAs (5.34%), 18,995 LncRNAs (49.23%) and 2,894 (7.5%) circRNAs. Chromosome 1 contributes for RNA transcription at most (10%). Bi-directional transcription contributes evenly for RNA biogenesis, in terms of 5′ to 3′ and 3′ to 5′. Despite the majority of circRNAs are exonic, antisense (1.49%), intergenic (0.035%), intragenic (1.69%), and intronic (6.29%) circRNAs should not be ignored. A single miRNA could interact with a multitude of circRNAs. Notably, CDR1as or ciRS-7 harbors 66 consecutive binding sites for miR-7-5p (previous miR-7), evidencing our pipeline. The majority of binding sites are perfect-matched (78.95%). Collectively, global landscape of RNAs sheds novel insights on RNA interacting mechanisms in human intervertebral disc degeneration. PMID:27542248

  2. Comparative Role of Disc Degeneration and Ligament Failure on Functional Mechanics of the Lumbar Spine

    PubMed Central

    Ellingson, Arin M.; Shaw, Miranda N.; Giambini, Hugo; An, Kai-Nan

    2015-01-01

    Understanding spinal kinematics is essential for distinguishing between pathological conditions of spine disorders, which ultimately lead to low back pain. It’s of high importance to understand how changes in mechanical properties affect the response of the lumbar spine, specifically in an effort to differentiate those associated with disc degeneration from ligamentous changes, allowing for more precise treatment strategies. To do this the goals of this study were twofold: 1) develop and validate a finite element (FE) model of the lumbar spine and 2) systematically alter the properties of the intervertebral disc and ligaments to define respective roles in functional mechanics. A three-dimensional non-linear FE model of the lumbar spine (L3-Sacrum) was developed and validated for pure moment bending. Disc degeneration and sequential ligament failure was modeled. Intersegmental range of motion (ROM) and bending stiffness was measured. The prediction of the FE model to moment loading in all three planes of bending showed very good agreement, where global and intersegmental ROM and bending stiffness of the model fell within one standard deviation of the in vitro results. Degeneration decreased ROM for all directions. Stiffness increased for all directions except axial rotation, where it initially increased then decreased for moderate and severe degeneration, respectively. Incremental ligament failure produced increased ROM and decreased stiffness. This effect was much more pronounced for all directions except lateral bending, which is minimally impacted by ligaments. These results indicate that lateral bending may be more apt to detect the subtle changes associated with degeneration, without being masked by associated changes of surrounding stabilizing structures. PMID:26404463

  3. Low Intensity Pulsed Ultrasound (LIPUS) for the treatment of intervertebral disc degeneration

    NASA Astrophysics Data System (ADS)

    Horne, Devante; Jones, Peter; Salgaonkar, Vasant; Adams, Matt; Ozilgen, B. Arda; Zahos, Peter; Tang, Xinyan; Liebenberg, Ellen; Coughlin, Dezba; Lotz, Jeffrey; Diederich, Chris

    2017-02-01

    Discogenic back pain presents a major public health issue, with current therapeutic interventions limited to short-term symptom relief without providing regenerative remedies for diseased intervertebral discs (IVD). Many of these interventions are invasive and can diminish the biomechanical integrity of the IVDs. Low intensity pulsed ultrasound (LIPUS) is a potential treatment option that is both non-invasive and regenerative. LIPUS has been shown to be a clinically effective method for the enhancement of wound and fracture healing. Recent in vitro studies have shown that LIPUS stimulation induces an upregulation functional matrix proteins and downregulation of inflammatory factors in cultured IVD cells. However, we do not know the effects of LIPUS on an in vivo model for intervertebral disc degeneration. The objective of this study was to show technical feasibility of building a LIPUS system that can target the rat tail IVD and apply this setup to a model for acute IVD degeneration. A LIPUS exposimetry system was built using a 1.0 MHz planar transducer and custom housing. Ex vivo intensity measurements demonstrated LIPUS delivery to the center of the rat tail IVD. Using an established stab-incision model for disc degeneration, LIPUS was applied for 20 minutes daily for five days. For rats that displayed a significant injury response, LIPUS treatment caused significant upregulation of Collagen II and downregulation of Tumor Necrosis Factor - α gene expression. Our preliminary studies indicate technical feasibility of targeted delivery of ultrasound to a rat tail IVD for studies of LIPUS biological effects.

  4. Annular puncture with tumor necrosis factor-alpha injection enhances painful behavior with disc degeneration in vivo.

    PubMed

    Lai, Alon; Moon, Andrew; Purmessur, Devina; Skovrlj, Branko; Laudier, Damien M; Winkelstein, Beth A; Cho, Samuel K; Hecht, Andrew C; Iatridis, James C

    2016-03-01

    , whereas pro-inflammatory cytokines might play a more important role in the level of pain, which might have resulted from enhanced DRG sensitization. These in vivo painful disc degeneration models with different severities of structural changes may be useful for investigating discogenic pain mechanisms and for screening therapies, although interpretations must note the differences between all surgically induced animal models and the human condition. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Hyaluronic Acid (HA)-Polyethylene glycol (PEG) as injectable hydrogel for intervertebral disc degeneration patients therapy

    NASA Astrophysics Data System (ADS)

    Putri Kwarta, Cityta; Widiyanti, Prihartini; Siswanto

    2017-05-01

    Chronic Low Back Pain (CLBP) is one health problem that is often encountered in a community. Inject-able hydrogels are the newest way to restore the disc thickness and hydration caused by disc degeneration by means of minimally invasive surgery. Thus, polymers can be combined to improve the characteristic properties of inject-able hydrogels, leading to use of Hyaluronic Acid (a natural polymer) and Polyethylene glycol (PEG) with Horse Radish Peroxide (HRP) cross linker enzymes. The swelling test results, which approaches were the ideal disc values, were sampled with variation of enzyme concentrations of 0.25 µmol/min/mL. The enzyme concentrations were 33.95%. The degradation test proved that the sample degradation increased along with the decrease of the HRP enzyme concentration. The results of the cytotoxicity assay with MTT assay method showed that all samples resulted in the 90% of living cells are not toxic. In vitro injection, models demonstrated that higher concentration of the enzymes was less state of gel which would rupture when released from the agarose gel. The functional group characterization shows the cross linking bonding in sample with enzyme adding. The conclusion of this study is PEG-HA-HRP enzyme are safe polymer composites which have a potential to be applied as an injectable hydrogel for intervertebral disc degeneration.

  6. Association between apparent diffusion coefficient and intervertebral disc degeneration in patients with ankylosing spondylitis

    PubMed Central

    Resorlu, Mustafa; Gokmen, Ferhat; Resorlu, Hatice; Adam, Gurhan; Akbal, Ayla; Cevizci, Sibel; Sariyildirim, Abdullah; Savas, Yilmaz; Guven, Mustafa; Aras, Adem Bozkurt

    2015-01-01

    Purpose: To assess the relation between ankylosing spondylitis (AS) and degenerative disc disease emerging in association with various intrinsic and extrinsic factors and to evaluate the correlation between degree of degeneration in intervertebral discs and apparent diffusion coefficient (ADC) values. Methods: Thirty-five patients with AS and a control group of 35 patients were included in the study. Three hundred fifty intervertebral discs were assessed in terms of degeneration by analyzing signal intensities and morphologies on T2 weighted series of a 1.5 Tesla magnetic resonance scanner. ADC values were determined in diffusion weighted images (DWI) using a “b value of 500 s/mm2”. Patients in the AS and control groups were compared in terms of intervertebral disc degeneration, and association between degree of degeneration and ADC values was analyzed. Results: The mean of total degeneration degrees for five lumbar intervertebral discs was significantly higher in the patients with AS compared to the control group (16.77±4.67 vs 13.00±4.08, respectively; P=0.001). When intervertebral discs were analyzed separately, disc degeneration was again significantly higher in patients with AS compared to the control group, with the exception of L5-S1. Age, cholesterol level, triglyceride level, duration of disease and BASFI index were significantly associated with degree of degeneration in patients with AS. A negative correlation was determined between disc degeneration and ADC value. Conclusion: AS is a risk factor for degenerative disc disease due to its systemic effects, the fact it leads to posture impairment and its inflammatory effects on the vertebrae. A decrease in ADC values is observed as degeneration worsens in degenerative disc disease. PMID:25785119

  7. Association Between Measures of Vertebral Endplate Morphology and Lumbar Intervertebral Disc Degeneration.

    PubMed

    Duran, Semra; Cavusoglu, Mehtap; Hatipoglu, Hatice Gul; Sozmen Cılız, Deniz; Sakman, Bulent

    2017-05-01

    The aim of this study was to evaluate the association between vertebral endplate morphology and the degree of lumbar intervertebral disc degeneration via magnetic resonance imaging (MRI). In total, 150 patients who met the inclusion criteria and were 20-60 years of age were retrospectively evaluated. Patients were evaluated for the presence of intervertebral disc degeneration or herniation, and the degree of degeneration was assessed at all lumbar levels. Vertebral endplate morphology was evaluated based on the endplate sagittal diameter, endplate sagittal concave angle (ECA), and endplate sagittal concave depth (ECD) on sagittal MRI. The association between intervertebral disc degeneration or herniation and endplate morphological measurements was analysed. In MRI, superior endplates (ie, inferior endplates of the superior vertebra) were concave and inferior endplates (ie, superior endplates of the inferior vertebra) were flat at all disc levels. A decrease in ECD and an increase in ECA were detected at all lumbar levels as disc degeneration increased (P < .05). At the L4-L5 and L5-S1 levels, a decrease in ECD and an increase in ECA were detected in the group with herniated lumbar discs (P < .05). There was no association between lumbar disc degeneration or herniation and endplate sagittal diameter at lumbar intervertebral levels (P > .05). At all levels, ECD of women was significantly lesser than that of men and ECA of women was significantly greater than that of men (P < .05). There is an association between vertebral endplate morphology and lumbar intervertebral disc degeneration. Vertebral endplates at the degenerated disc level become flat; the severity of this flattening is correlated with the degree of disc degeneration. Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

  8. The role of interleukin-1 in the pathogenesis of human Intervertebral disc degeneration

    PubMed Central

    Le Maitre, Christine Lyn; Freemont, Anthony J; Hoyland, Judith Alison

    2005-01-01

    In this study, we investigated the hypotheses that in human intervertebral disc (IVD) degeneration there is local production of the cytokine IL-1, and that this locally produced cytokine can induce the cellular and matrix changes of IVD degeneration. Immunohistochemistry was used to localize five members of the IL-1 family (IL-1α, IL-1β, IL-1Ra (IL-1 receptor antagonist), IL-1RI (IL-1 receptor, type I), and ICE (IL-1β-converting enzyme)) in non-degenerate and degenerate human IVDs. In addition, cells derived from non-degenerate and degenerate human IVDs were challenged with IL-1 agonists and the response was investigated using real-time PCR for a number of matrix-degrading enzymes, matrix proteins, and members of the IL-1 family. This study has shown that native disc cells from non-degenerate and degenerate discs produced the IL-1 agonists, antagonist, the active receptor, and IL-1β-converting enzyme. In addition, immunopositivity for these proteins, with the exception of IL-1Ra, increased with severity of degeneration. We have also shown that IL-1 treatment of human IVD cells resulted in increased gene expression for the matrix-degrading enzymes (MMP 3 (matrix metalloproteinase 3), MMP 13 (matrix metalloproteinase 13), and ADAMTS-4 (a disintegrin and metalloproteinase with thrombospondin motifs)) and a decrease in the gene expression for matrix genes (aggrecan, collagen II, collagen I, and SOX6). In conclusion we have shown that IL-1 is produced in the degenerate IVD. It is synthesized by native disc cells, and treatment of human disc cells with IL-1 induces an imbalance between catabolic and anabolic events, responses that represent the changes seen during disc degeneration. Therefore, inhibiting IL-1 could be an important therapeutic target for preventing and reversing disc degeneration. PMID:15987475

  9. MRI Quantification of Human Spine Cartilage Endplate Geometry: Comparison With Age, Degeneration, Level, and Disc Geometry

    PubMed Central

    DeLucca, John F.; Peloquin, John M.; Smith, Lachlan J.; Wright, Alexander C.; Vresilovic, Edward J.; Elliott, Dawn M.

    2017-01-01

    Geometry is an important indicator of disc mechanical function and degeneration. While the geometry and associated degenerative changes in the nucleus pulposus and the annulus fibrosus are well-defined, the geometry of the cartilage endplate (CEP) and its relationship to disc degeneration are unknown. The objectives of this study were to quantify CEP geometry in three dimensions using an MRI FLASH imaging sequence and evaluate relationships between CEP geometry and age, degeneration, spinal level, and overall disc geometry. To do so, we assessed the MRI-based measurements for accuracy and repeatability. Next, we measured CEP geometry across a larger sample set and correlated CEP geometric parameters to age, disc degeneration, level, and disc geometry. The MRI-based measures resulted in thicknesses (0.3–1 mm) that are comparable to prior measurements of CEP thickness. CEP thickness was greatest at the anterior/posterior (A/P) margins and smallest in the center. The CEP A/P thickness, axial area, and lateral width decreased with age but were not related to disc degeneration. Age-related, but not degeneration-related, changes in geometry suggest that the CEP may not follow the progression of disc degeneration. Ultimately, if the CEP undergoes significant geometric changes with aging and if these can be related to low back pain, a clinically feasible translation of the FLASH MRI-based measurement of CEP geometry presented in this study may prove a useful diagnostic tool. PMID:27232974

  10. Paeoniflorin inhibits nucleus pulposus cell apoptosis by regulating the expression of Bcl-2 family proteins and caspase-9 in a rabbit model of intervertebral disc degeneration

    PubMed Central

    SHI, LIJUN; TENG, HONGLIN; ZHU, MINYU; LI, CHI; HUANG, KELUN; CHEN, BI; DAI, YUSEN; WANG, JING

    2015-01-01

    Apoptosis plays a key role in the pathogenesis of internal disc disruption (IDD); therefore, the inhibition of apoptosis may offer a novel approach for treating IDD diseases. The aim of the present study was to investigate the effects and the underlying mechanisms of paeoniflorin through the detection of relevant indicators in a rabbit model of IDD. In total, 144 rabbits were used in the study and divided into four groups (n=36 per group). Rabbits successfully modeled with IDD received an intragastric injection of 120 mg/kg·day paeoniflorin (high-dose group), 30 mg/kg·day paeoniflorin (low-dose group) or saline (model saline group), while rabbits without IDD were used as a normal control group. The apoptosis rate of disc nucleus pulposus cells was detected using flow cytometry. In addition, the expression levels of Bcl-2, Bax and caspase-9 in the disc tissues were detected using immunohistochemistry and western blot analysis prior to and following the treatment. The results indicated that the expression levels of Bax in the low- and high-dose paeoniflorin groups were significantly reduced, while the Bcl-2 expression levels were significantly increased when compared with the model saline group (P<0.01). In addition, the expression levels of cleaved caspase-3 and cleaved caspase-9 were reduced in the low- and high-dose paeoniflorin groups, as compared with the model saline group (P<0.05). Furthermore, the average apoptotic index of the high- and low-dose paeoniflorin groups was decreased when compared with the model saline group (P<0.05). In conclusion, paeoniflorin was demonstrated to inhibit the apoptosis of nucleus pulposus cells and the activation of caspase-3 and caspase-9 through the regulation of Bcl-2 family protein expression. These results provide an experimental basis for the future treatment of IDD with paeoniflorin. PMID:26170945

  11. Disc distraction shows evidence of regenerative potential in degenerated intervertebral discs as evaluated by protein expression, magnetic resonance imaging, and messenger ribonucleic acid expression analysis.

    PubMed

    Guehring, Thorsten; Omlor, Georg W; Lorenz, Helga; Engelleiter, Karl; Richter, Wiltrud; Carstens, Claus; Kroeber, Markus

    2006-07-01

    An animal model of degeneration was used to determine the effects of disc distraction, and was evaluated with magnetic resonance imaging (MRI) as well as gene and protein expression levels. To investigate gene expression and MRI effects of distraction. Disc degeneration can result from hyper-physiologic loading. Distracted discs with degeneration showed histologic signs of tissue recovery. There were 18 rabbits that underwent 28 days of compression (200 N) to induce moderate disc degeneration followed by 28 days of distraction (120 N; attached and loaded distraction device) or sham distraction (attached but unloaded distraction device). Comparison was performed with 56 days of compressed discs without distraction. Quantitative outcome measures were MRI signal intensity and gene expression analysis to determine: messenger ribonucleic acid levels for extracellular matrix genes, including collagen 1, collagen 2, biglycan, decorin, aggrecan, fibromodulin, and osteonectin; and matrix-regulative genes, including matrix metalloproteinase-13, tissue-inhibitor of matrix metalloproteinase-1, and bone morphogenetic protein (BMP)-2. Immunohistology was performed for collagen 2 and BMP-2 to label cells semiquantitatively by staining of the cell-surrounding matrix. A total of 28 days of compression decreased signal intensity. Distraction over the same period reestablished physiologic signal intensity, however, a persistent reduction was found in sham distraction. Distraction resulted in gene expression up-regulation of collagen 1 (5.4-fold), collagen 2 (5.5-fold), biglycan (7.7-fold), and decorin (3.4-fold), while expression of fibromodulin (0.16-fold), tissue-inhibitor of matrix metalloproteinase-1 (0.05-fold), and BMP-2 (0.15-fold) was decreased, as compared with 56 days compression. Distracted discs showed more BMP-2 (19.67 vs. 3.67 in 56 days compression) and collagen 2 (18.67 vs. 11.33 in 56 days compression) positive cells per field. Distraction results in disc rehydration

  12. Role of biomechanics on intervertebral disc degeneration and regenerative therapies: What needs repairing in the disc and what are promising biomaterials for its repair?

    PubMed Central

    Iatridis, James C.; Nicoll, Steven B.; Michalek, Arthur J.; Walter, Benjamin A.; Gupta, Michelle S.

    2013-01-01

    Background Context Degeneration and injuries of the intervertebral disc result in large alterations in biomechanical behaviors. Repair strategies using biomaterials can be optimized based on biomechanical and biological requirements. Purpose To review current literature on 1) effects of degeneration, simulated degeneration, and injury on biomechanics of the intervertebral disc with special attention paid to needle puncture injuries which are a pathway for diagnostics and regenerative therapies; and 2) promising biomaterials for disc repair with a focus on how those biomaterials may promote biomechanical repair. Study Design/Setting A narrative review to evaluate the role of biomechanics on disc degeneration and regenerative therapies with a focus on what biomechanical properties need to be repaired and how to evaluate and accomplish such repairs using biomaterials. Model systems for screening of such repair strategies are also briefly described. Methods Papers were selected from two main Pubmed searches using keywords: intervertebral AND biomechanics (1823 articles) and intervertebral AND biomaterials (361 articles). Additional keywords (injury, needle puncture, nucleus pressurization, biomaterials, hydrogel, sealant, tissue engineering) were used to narrow articles to the topics most relevant to this review. Results Degeneration and acute disc injuries have the capacity to influence nucleus pulposus pressurization and annulus fibrosus integrity, which are necessary for effective disc function, and therefore, require repair. Needle injection injuries are of particular clinical relevance with potential to influence disc biomechanics, cellularity, and metabolism, yet these effects are localized or small, and more research is required to evaluate and reduce potential clinical morbidity using such techniques. NP replacement strategies, such as hydrogels, are required to restore NP pressurization or lost volume. AF repair strategies, including crosslinked hydrogels

  13. Factors associated with lumbar intervertebral disc degeneration in the elderly.

    PubMed

    Hangai, Mika; Kaneoka, Koji; Kuno, Shinya; Hinotsu, Shiro; Sakane, Masataka; Mamizuka, Naotaka; Sakai, Shinsuke; Ochiai, Naoyuki

    2008-01-01

    Lumbar intervertebral disc degeneration (DD) precedes degenerative diseases of the lumbar spine. Various factors in addition to normal aging are reported to be associated with DD, and recently atherosclerosis and risk factors for cardiovascular diseases (cardiovascular risk factors) have received much attention; however, the links between these risk factors and DD are unclear. By correlating magnetic resonance images (MRI) with suspected degenerative disc risk factors such as obesity, cardiovascular risk factors, and atherosclerosis, we hope to clarify the factors associated with DD. An observational study. Two hundred seventy adults (51-86 years old) who participated in a health promotion program. DD evaluated based on the signal intensity of MR T2-weighted mid-sagittal images of the lumbar spine. Age, gender, body mass index (BMI), low-density lipoprotein cholesterol (LDLc), triglyceride (TG), glycosylated hemoglobin (HbA(1c)), brachial-ankle pulse wave velocity (baPWV) as an index of atherosclerosis, osteo-sono-assessment index (OSI) calculated from quantitative ultrasound assessment of the calcaneus as an index of bone mineral density (BMD), history of low back pain (LBP), smoking and drinking habits, and physical loading related to occupations and sports were assessed. The univariate relationships between DD and the variables were evaluated, and finally, odds ratios (OR) and 95% confidence intervals (CI) for the associations of each factor with DD were calculated using logistic regression at each disc level. Aging correlated significantly with DD of L1/2 (OR, 2.14), L2/3 (OR, 3.56), L3/4 (OR, 2.84), and L4/5 (OR, 3.05); high BMI, with L2/3 (OR, 2.98), L3/4 (OR, 3.58), L4/5 (OR, 2.32), and L5/S1 (OR, 3.34); high LDLc, with L4/5 (OR, 2.65); occupational lifting, with L1/2 (OR, 4.25); and sports activities, with L5/S1 (OR, 3.36). Aging, high BMI, high LDLc, occupational lifting, and sports activities are associated with DD. The results of this study raise our

  14. Qualitative and quantitative assessment of degeneration of cervical intervertebral discs and facet joints.

    PubMed

    Walraevens, Joris; Liu, Baoge; Meersschaert, Joke; Demaerel, Philippe; Delye, Hans; Depreitere, Bart; Vander Sloten, Jos; Goffin, Jan

    2009-03-01

    Degeneration of intervertebral discs and facet joints is one of the most frequently encountered spinal disorders. In order to describe and quantify degeneration and evaluate a possible relationship between degeneration and biomechanical parameters, e.g., the intervertebral range of motion and intradiscal pressure, a scoring system for degeneration is mandatory. However, few scoring systems for the assessment of degeneration of the cervical spine exist. Therefore, two separate objective scoring systems to qualitatively and quantitatively assess the degree of cervical intervertebral disc and facet joint degeneration were developed and validated. The scoring system for cervical disc degeneration consists of three variables which are individually scored on neutral lateral radiographs: "height loss" (0-4 points), "anterior osteophytes" (0-3 points) and "endplate sclerosis" (0-2 points). The scoring system for facet joint degeneration consists of four variables which are individually scored on neutral computed tomography scans: "hypertrophy" (0-2 points), "osteophytes" (0-1 point), "irregularity" on the articular surface (0-1 point) and "joint space narrowing" (0-1 point). Each variable contributes with varying importance to the overall degeneration score (max 9 points for the scoring system of cervical disc degeneration and max 5 points for facet joint degeneration). Degeneration of 20 discs and facet joints of 20 patients was blindly assessed by four raters: two neurosurgeons (one senior and one junior) and two radiologists (one senior and one junior), firstly based on first subjective impression and secondly using the scoring systems. Measurement errors and inter- and intra-rater agreement were determined. The measurement error of the scoring system for cervical disc degeneration was 11.1 versus 17.9% of the subjective impression results. This scoring system showed excellent intra-rater agreement (ICC = 0.86, 0.75-0.93) and excellent inter-rater agreement (ICC = 0

  15. A Histopathological Scheme for the Quantitative Scoring of Intervertebral Disc Degeneration and the Therapeutic Utility of Adult Mesenchymal Stem Cells for Intervertebral Disc Regeneration

    PubMed Central

    Shu, Cindy C.; Smith, Margaret M.; Smith, Susan M.; Dart, Andrew J.; Little, Christopher B.; Melrose, James

    2017-01-01

    The purpose of this study was to develop a quantitative histopathological scoring scheme to evaluate disc degeneration and regeneration using an ovine annular lesion model of experimental disc degeneration. Toluidine blue and Haematoxylin and Eosin (H&E) staining were used to evaluate cellular morphology: (i) disc structure/lesion morphology; (ii) proteoglycan depletion; (iii) cellular morphology; (iv) blood vessel in-growth; (v) cell influx into lesion; and (vi) cystic degeneration/chondroid metaplasia. Three study groups were examined: 5 × 5 mm lesion; 6 × 20 mm lesion; and 6 × 20 mm lesion plus mesenchymal stem cell (MSC) treatment. Lumbar intervertebral discs (IVDs) were scored under categories (i–vi) to provide a cumulative score, which underwent statistical analysis using STATA software. Focal proteoglycan depletion was associated with 5 × 5 mm annular rim lesions, bifurcations, annular delamellation, concentric and radial annular tears and an early influx of blood vessels and cells around remodeling lesions but the inner lesion did not heal. Similar features in 6 × 20 mm lesions occurred over a 3–6-month post operative period. MSCs induced a strong recovery in discal pathology with a reduction in cumulative histopathology degeneracy score from 15.2 to 2.7 (p = 0.001) over a three-month recovery period but no recovery in carrier injected discs. PMID:28498326

  16. Solute transport in intervertebral disc: experiments and finite element modeling.

    PubMed

    Das, D B; Welling, A; Urban, J P G; Boubriak, O A

    2009-04-01

    Loss of nutrient supply to the human intervertebral disc (IVD) cells is thought to be a major cause of disc degeneration in humans. To address this issue, transport of molecules of different size have been analyzed by a combination of experimental and modeling studies. Solute transport has been compared for steady-state and transient diffusion of several different solutes with molecular masses in the range 3-70 kDa, injected into parts of the disc where degeneration is thought most likely to occur first and into the blood supply to the disc. Diffusion coefficients of fluorescently tagged dextran molecules of different molecular weights have been measured in vitro using the concentration gradient technique in thin specimens of disc outer annulus and nucleus pulposus. Diffusion coefficients were found to decrease with molecular weight following a nonlinear relationship. Diffusion coefficients changed more rapidly for solutes with molecular masses less than 10 kDa. Although unrealistic or painful, solutes injected directly into the disc achieve the largest disc coverage with concentrations that would be high enough to be of practical use. Although more practical, solutes injected into the blood supply do not penetrate to the central regions of the disc and their concentrations dissipate more rapidly. Injection into the disc would be the best method to get drugs or growth factors to regions of degeneration in IVDs quickly; else concentrations of solute must be kept at a high value for several hours in the blood supply to the discs.

  17. Evidence for an Important Role of Smad-7 in Intervertebral Disc Degeneration

    PubMed Central

    Li, Bo; Su, Yi-Jun; Zheng, Xin-Feng; Yang, Yue-Hua; Jiang, Sheng-Dan

    2015-01-01

    Smad-7 inhibited the transforming growth factor beta (TGF-β)-induced proteoglycan synthesis in chondrocytes and completely antagonized the effect of TGF-β on the proliferation of the cells. The aim of this study was to evaluate the contribution of Smad-7 to the pathophysiology of disc degeneration by determining the expression of Smad-7 in the degenerative intervertebral discs and its effect on the extracellular matrix metabolism of disc cells. Instability of the lumbar spine produced by imbalanced dynamic and static forces was used to induce intervertebral disc degeneration in rats. The expression of Smad-7 was assessed by the immunohistochemical method. Disc cell apoptosis was detected by in situ TUNEL staining. The effect of Smad-7 overexpression on the matrix metabolism of disc cells was analyzed in vitro by real-time polymerase chain reaction (PCR) and Western blotting. Finally, intradiscal injection of the Smad-7 overexpression lentivirus was performed to evaluate the in vivo effect of Smad-7 on disc degeneration. Radiographic and histomorphological examinations showed that lumbar disc degeneration became more and more severe in the rats with induced instability. Immunohistochemical observation demonstrated increasing protein expression of Smad-7 in the degenerative discs. A significantly positive correlation was found between Smad-7 expression and the degree of disc degeneration and between Smad-7 expression and disc cell apoptosis. Overexpression of Smad-7 in disc cells inhibited the expression of TGF-β1, collagen type-I, collagen type-II, and aggrecan and promoted the expression of MMP-13, but did not change the expression of ADAMTS-5. The in vivo findings illustrated that intradiscal injection of lentivirus vector with Smad-7 overexpression accelerated the progress of disc degeneration. In conclusion, Smad-7 was highly expressed in the degenerative discs. Overexpression of Smad-7 weakened the protective role of TGF-β and accelerated the progress of

  18. Effect of calcitonin pretreatment on naturally occurring intervertebral disc degeneration in guinea pig

    PubMed Central

    Jiang, Xiaohua; Tian, Faming; Wang, Wenya; Yan, Jinyin; Liu, Huanjiang; Liu, Binbin; Song, Huiping; Zhang, Yingze; Shen, Yong; Zhang, Liu

    2015-01-01

    Introduction: Our previous study suggested protective effects of calcitonin (CT) on experimental osteoarthritis. The aim of the present study was to provide evidence of whether CT pretreatment could prevent naturally occurring intervertebral disc degeneration in guinea pigs. Methods: Forty-two 3 months old female guinea pigs were randomly assigned into 2 groups as follows: Twenty-four were treated by normal saline as control group and sacrificed at 3, 6, 9 and 12 months of age (6 animals at each time point), the other 18 were received salmon CT (8 ug/kg/day, everyday) treatment at 3 months of age and sacrificed at the age of 6, 9 and 12 months respectively. Van Gieson stain and the histological score were used to identify the histological changes of the lumbar intervertebral discs. The disc height and vertebral body height were measured. Immunohistochemistry measurements for glycosaminoglycan, type II collagen, and matrix metalloprotease (MMP)-1 expressions were performed. Bone quality and microstructural changes in the L3-6 lumbar vertebral bodies were assessed by bone mineral density (BMD), micro-CT analysis and biomechanical testing. Results: Histological analysis indicated significantly higher disc degeneration scores in 9-month-old guinea pigs in comparison with younger animals, and grew higher with increasing age. CT treatment significantly reduced the histological score, and increased the disc height and the ratio to vertebral body height in 12 months old animals, as well as upregulated the glycosaminoglycan, type II collagen and inhibited the MMP-1 expression. Micro-CT analysis showed decreased percent bone volume (BV/TV) and increased trabecular separation (Tb.Sp), structural model index (SMI) in 12 months old animals in comparison with the younger animals. Markedly increased BV/TV and decreased Tb.Sp were observed in CT treated animals when compared with control animals. The biomechanical properties including maximum load, maximum stress, yield stress and

  19. [Research progress of cellular senescence and senescent secretary phenotype in intervertebral disc degeneration].

    PubMed

    Wang, Feng; Zheng, Chenjingmei; Wu, Xiaotao

    2012-12-01

    To summarize the role of cellular senescence and senescent secretary phenotype in the intervertebral disc (IVD) degeneration. Relevant articles that discussed the roles of cellular senescence in the IVD degeneration were extensively reviewed, and retrospective and comprehensive analysis was performed. The senescent phenomenon during IVD degeneration, senescent secretary phenotype of the disc cells, senescent pathways within the IVD microenvironment, as well as the anti-senescent approaches for IVD regeneration were systematically reviewed. During aging and degeneration, IVD cells gradually and/or prematurely undergo senescence by activating p53-p21-retinoblastoma (RB) or p161NK4A-RB senescent pathways. The accumulation of senescent cells not only decreases the self-renewal ability of IVD, but also deteriorates the disc microenvironment by producing more inflammatory cytokines and matrix degrading enzymes. More specific senescent biomarkers are required to fully understand the phenotype change of senescent disc cells during IVD degeneration. Molecular analysis of the senescent disc cells and their intracellular signaling pathways are needed to get a safer and more efficient anti-senescence strategy for IVD regeneration. Cellular senescence is an important mechanism by which IVD cells decrease viability and degenerate biological behaviors, which provide a new thinking to understand the pathogenesis of IVD degeneration.

  20. Lovastatin prevents discography-associated degeneration and maintains the functional morphology of intervertebral discs.

    PubMed

    Hu, Ming-Hsiao; Yang, Kai-Chiang; Chen, Yeong-Jang; Sun, Yuan-Hui; Yang, Shu-Hua

    2014-10-01

    Discography is an important diagnostic approach to identify the painful discs. However, the benefit of discography, a procedure involving needle puncture and injection of the diagnostic agent into the intervertebral disc, is controversial and has been reported to be associated with accelerated degeneration. To investigate the effect of lovastatin on the prevention of degeneration caused by a discography simulation procedure in rat caudal discs. In vivo study using rat caudal discs. A single flexible 27-gauge needle puncture into rat caudal discs was performed under fluoroscopic monitoring. Different concentrations (0.1, 1, 5, and 10 μM) of lovastatin were prepared and injected into randomly chosen caudal discs. RNA expression of selected genes, histologic, and immunohistochemical staining were performed to evaluate the phenotypic effects of lovastatin on rat caudal discs. Simulation of the discography procedure by puncturing the rat caudal discs with a 27-gauge needle and injection of saline solution induced degenerative changes in the nucleus pulposus with minimal damage to the annulus fibrosus. Aggrecan, Type II collagen, and SOX9 expressions were upregulated, whereas Type I collagen expression was significantly suppressed in discs treated with 5 and 10 μM lovastatin. Discs treated with 5 and 10 μM lovastatin were subjected to alcian blue staining and immunohistochemistry that revealed higher levels of glycosaminoglycans and an increase in the number of cells producing S-100 proteins, Type II collagen, and bone morphogenetic protein-2 (BMP-2), respectively. The most effective phenotypic repair was observed in discs treated with 10 μM lovastatin. Intradiscal administration of lovastatin solution upregulated the expressions of BMP-2 and SOX9 and promoted chondrogenesis of rat caudal discs after needle puncture and substance injection. Therefore, we suggest that lovastatin promotes disc repair and can be used as a potential therapeutic agent for biological

  1. Evaluation of canine intervertebral disc degeneration in colour-coded computed tomography.

    PubMed

    Harder, Lisa K; Galindo-Zamora, Vladimir; Beyerbach, Martin; Nolte, Ingo; Wefstaedt, Patrick

    2015-01-01

    Canine intervertebral disc degeneration can lead to intervertebral disc disease. Mild degenerative changes in the structure of the canine intervertebral disc can be identified in magnetic resonance images, whereas these changes are not visible in computed tomographic images. Therefore, one aim of this study was to detect whether colour-coded computed tomography enhances the visibility of mild degenerative changes in the canine disc structure compared to non-contrast computed tomography. Furthermore, the study aimed to detect if intervertebral disc degeneration could be classified with a higher reliability in colour-coded images than in non-contrast images. Computed tomographic image studies of 144 canine intervertebral discs were coloured using three different lookup tables. Canine intervertebral disc degeneration was evaluated by three observers using a 5-grade classification system and compared to the evaluation of non-contrast CT and MRI images. A moderate to almost perfect intraobserver and a moderate to substantial interobserver agreement were found depending on the used colour code. On comparing non-contrast and colour-coded CT significant differences were found by one observer only. Significant differences in evaluation were found in grading intervertebral disc degeneration in MRI and colour-coded CT. Intervertebral disc degeneration could not be classified with a higher reliability on colour-coded images compared to non-contrast images. Furthermore, colour-coded CT did not enhance the visibility of mild degenerative changes in disc structure compared to non-contrast CT. However, the better intraobserver agreement and the subjective impression of the observers highlighted that the usage of colour encoded CT data sets with a wide range of tonal values of few primary and secondary colours may facilitate evaluation.

  2. Sitting versus standing: does the intradiscal pressure cause disc degeneration or low back pain?

    PubMed

    Claus, Andrew; Hides, Julie; Moseley, G Lorimer; Hodges, Paul

    2008-08-01

    Studies of lumbar intradiscal pressure (IDP) in standing and upright sitting have mostly reported higher pressures in sitting. It was assumed clinically that flexion of the lumbar spine in sitting relative to standing, caused higher IDP, disc degeneration or rupture, and low back pain. IDP indicates axial compressive load upon a non-degenerate disc, but provides little or no indication of shear, axial rotation or bending. This review is presented in two main parts. First, in vivo IDP data in standing and upright sitting for non-degenerate discs are comprehensively reviewed. As methodology, results and interpretations varied between IDP studies, in vivo studies measuring spinal shrinkage and spinal internal-fixator loads to infer axial compressive load to the discs are also reviewed. When data are considered together, it is clear that IDP is often similar in standing and sitting. Secondly, clinical assumptions related to IDP in sitting are considered in light of basic and epidemiologic studies. Current studies indicate that IDP in sitting is unlikely to pose a threat to non-degenerate discs, and sitting is no worse than standing for disc degeneration or low back pain incidence. If sitting is a greater threat for development of low back pain than standing, the mechanism is unlikely to be raised IDP.

  3. A Novel Catechol-O-Methyltransferase Variant Associated with Human Disc Degeneration

    PubMed Central

    Gruber, Helen E.; Sha, Wei; Brouwer, Cory R.; Steuerwald, Nury; Hoelscher, Gretchen L.; Hanley, Edward N. Jr.

    2014-01-01

    Background: Disc degeneration and its associated low back pain are a major health care concern causing disability with a prominent role in this country's medical, social and economic structure. Low back pain is devastating and influences the quality of life for millions. Low back pain lifetime prevalence approximates 80% with an estimated direct cost burden of $86 billion per year. Back pain patients incur higher costs, greater health care utilization, and greater work loss than patients without back pain. Methods: Research was performed following approval of our Institutional Review Board. DNA was isolated, processed and amplified using routine techniques. Amplified DNA was hybridized to Affymetrix Genome-Wide Human SNP Arrays. Quality control and genotyping analysis were performed using Affymetrix Genotyping Console. The Birdseed v2 algorithm was used for genotyping analysis. 2589 SNPs were selected a priori to enter statistical analysis using lotistic regression in SAS. Results: Our objective was to search for novel single nucleotide polymorphisms (SNPs) associated with disc degeneration. Four SNPs were found to have a significant relationship to disc degeneration; three are novel. Rs165656, a new SNP found to be associated with disc degeneration, was in catechol-O-methyltransferase (COMT), a gene with well-recognized pain involvement, especially in female subjects (p=0.01). Analysis confirmed the previously association between COMT SNP rs4633 and disc degeneration. We also report two novel disc degeneration-related SNPs (rs2095019 and rs470859) located in intergenic regions upstream to thrombospondin 2. Conclusions: Findings contribute to the challenging field of disc degeneration and pain, and are important in light of the high clinical relevance of low back pain and the need for improved understanding of its fundamental basis. PMID:24904231

  4. MRI quantification of human spine cartilage endplate geometry: Comparison with age, degeneration, level, and disc geometry.

    PubMed

    DeLucca, John F; Peloquin, John M; Smith, Lachlan J; Wright, Alexander C; Vresilovic, Edward J; Elliott, Dawn M

    2016-08-01

    Geometry is an important indicator of disc mechanical function and degeneration. While the geometry and associated degenerative changes in the nucleus pulposus and the annulus fibrosus are well-defined, the geometry of the cartilage endplate (CEP) and its relationship to disc degeneration are unknown. The objectives of this study were to quantify CEP geometry in three dimensions using an MRI FLASH imaging sequence and evaluate relationships between CEP geometry and age, degeneration, spinal level, and overall disc geometry. To do so, we assessed the MRI-based measurements for accuracy and repeatability. Next, we measured CEP geometry across a larger sample set and correlated CEP geometric parameters to age, disc degeneration, level, and disc geometry. The MRI-based measures resulted in thicknesses (0.3-1 mm) that are comparable to prior measurements of CEP thickness. CEP thickness was greatest at the anterior/posterior (A/P) margins and smallest in the center. The CEP A/P thickness, axial area, and lateral width decreased with age but were not related to disc degeneration. Age-related, but not degeneration-related, changes in geometry suggest that the CEP may not follow the progression of disc degeneration. Ultimately, if the CEP undergoes significant geometric changes with aging and if these can be related to low back pain, a clinically feasible translation of the FLASH MRI-based measurement of CEP geometry presented in this study may prove a useful diagnostic tool. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1410-1417, 2016.

  5. Population average T2 MRI maps reveal quantitative regional transformations in the degenerating rabbit intervertebral disc that vary by lumbar level.

    PubMed

    Martin, John T; Collins, Christopher M; Ikuta, Kensuke; Mauck, Robert L; Elliott, Dawn M; Zhang, Yeija; Anderson, D Greg; Vaccaro, Alexander R; Albert, Todd J; Arlet, Vincent; Smith, Harvey E

    2015-01-01

    Magnetic resonance imaging (MRI) with T2-weighting is routinely performed to assess intervertebral disc degeneration. Standard clinical evaluations of MR images are qualitative, however, and do not focus on region-specific alterations in the disc. Utilizing a rabbit needle puncture model, T2 mapping was performed on injured discs to develop a quantitative description of the degenerative process following puncture. To do so, an 18G needle was inserted into four discs per rabbit (L3/L4 to L6/L7) and T2 maps were generated pre- and 4 weeks post-injury. Individual T2 maps were normalized to a disc-specific coordinate system and then averaged for pre- and post-injury population composite T2 maps. We also developed a method to automatically segment the nucleus pulposus by fitting the NP region of the T2 maps with modified 2-D and 3-D Gaussian distribution functions. Puncture injury produced alterations in MR signal intensity in a region-specific manner mirroring human degeneration. Population average T2 maps provided a quantitative representation of the injury response, and identified deviations of individual degenerate discs from the pre-injury population. We found that the response to standardized injury was modest at lower lumbar levels, likely as a result of increased disc dimensions. These tools will be valuable for the quantitative characterization of disc degeneration in future clinical and pre-clinical studies. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo

    PubMed Central

    Chen, Deheng; Xia, Dongdong; Pan, Zongyou; Xu, Daoliang; Zhou, Yifei; Wu, Yaosen; Cai, Ningyu; Tang, Qian; Wang, Chenggui; Yan, Meijun; Zhang, Jing Jie; Zhou, Kailiang; Wang, Quan; Feng, Yongzeng; Wang, Xiangyang; Xu, Huazi; Zhang, Xiaolei; Tian, Naifeng

    2016-01-01

    Intervertebral disc degeneration (IDD) is a complicated process that involves both cellular apoptosis and senescence. Metformin has been reported to stimulate autophagy, whereas autophagy is shown to protect against apoptosis and senescence. Therefore, we hypothesize that metformin may have therapeutic effect on IDD through autophagy stimulation. The effect of metformin on IDD was investigated both in vitro and in vivo. Our study showed that metformin attenuated cellular apoptosis and senescence induced by tert-butyl hydroperoxide in nucleus pulposus cells. Autophagy, as well as its upstream regulator AMPK, was activated by metformin in nucleus pulposus cells in a dose- and time-dependent manner. Inhibition of autophagy by 3-MA partially abolished the protective effect of metformin against nucleus pulposus cells' apoptosis and senescence, indicating that autophagy was involved in the protective effect of metformin on IDD. In addition, metformin was shown to promote the expression of anabolic genes such as Col2a1 and Acan expression while inhibiting the expression of catabolic genes such as Mmp3 and Adamts5 in nucleus pulposus cells. In vivo study illustrated that metformin treatment could ameliorate IDD in a puncture-induced rat model. Thus, our study showed that metformin could protect nucleus pulposus cells against apoptosis and senescence via autophagy stimulation and ameliorate disc degeneration in vivo, revealing its potential to be a therapeutic agent for IDD. PMID:27787519

  7. Methodology to Calibrate Disc Degeneration in the Cervical Spine During Cyclic Fatigue Loading.

    PubMed

    Masoudi, Aidin; Fama, Daniel; Yoganandan, Narayan; Snyder, Brian

    2015-01-01

    Prolonged exposure to vibrational working conditions can cause neck, back, and shoulder pain. Mechanical degradation of soft tissues resulting from this type of fatigue was experimentally shown to contribute to endplate and compression fractures. However, effects of repetitive subfailure loading on intervertebral disc (IVD) behavior have not been well defined. This manuscript describes a methodology to experimentally characterize changes in cervical spine IVD material properties under fatigue. Bone-disc-bone spinal units with intact ligaments obtained from human cervical spines were obtained and a lack of bony or soft tissue degeneration was confirmed using X-ray and MRI scans. Cranial and caudal specimen extents were fixed in PMMA to facilitate attachment to testing devices. Baseline response was quantified using flexion/extension pure moment protocols. Specimens were immersed in a 34-deg-C saline bath and allowed to acclimate for one hour. A stress-relaxation test was then performed and viscoelasticity quantified using a quasi linear viscoelastic (QLV) material model. Fatigue testing was performed for up to 50,000 cycles with intermittent viscoelasticity, pure moment testing, and imaging scans performed to quantify cycle-dependent changes in disc properties. Preliminary results demonstrated progressive changes in viscoelasticity and bending response of cervical spine segments with increasing number of load cycles. This procedure will be used to quantify degradation of the IVD under repetitive compressive loads, focusing on effects of loading magnitude and frequency.

  8. Aging and age related stresses: a senescence mechanism of intervertebral disc degeneration.

    PubMed

    Wang, F; Cai, F; Shi, R; Wang, X-H; Wu, X-T

    2016-03-01

    Intervertebral disc (IVD) degeneration is a complicated process that involves both age-related change and tissue damage caused by multiple stresses. In a degenerative IVD, cellular senescence accumulates and is associated with reduced proliferation, compromised self-repair, increased inflammatory response, and enhanced catabolic metabolism. In this review, we decipher the senescence mechanism of IVD degeneration (IVDD) by interpreting how aging coordinates with age-related, microenvironment-derived stresses in promoting disc cell senescence and accelerating IVDD. After chronic and prolonged replication, cell senescence may occur as a natural part of the disc aging process, but can potentially be accelerated by growth factor deficiency, oxidative accumulation, and inflammatory irritation. While acute disc injury, excessive mechanical overloading, diabetes, and chronic tobacco smoking contribute to the amplification of senescence-inducing stresses, the avascular nature of IVD impairs the immune-clearance of the senescent disc cells, which accumulate in cell clusters, demonstrate inflammatory and catabolic phenotypes, deteriorate disc microenvironment, and accelerate IVDD. Anti-senescence strategies, including telomerase transduction, supply of growth factors, and blocking cell cycle inhibitors, have been shown to be feasible in rescuing disc cells from early senescence, but their efficiency for disc regeneration requires more in vivo validations. Guidelines dedicated to avoiding or alleviating senescence-inducing stresses might decelerate cellular senescence and benefit patients with IVD degenerative diseases. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  9. Glucosamine and chondroitin sulfate supplementation to treat symptomatic disc degeneration: Biochemical rationale and case report

    PubMed Central

    van Blitterswijk, Wim J; van de Nes, Jos CM; Wuisman, Paul IJM

    2003-01-01

    Background Glucosamine and chondroitin sulfate preparations are widely used as food supplements against osteoarthritis, but critics are skeptical about their efficacy, because of the lack of convincing clinical trials and a reasonable scientific rationale for the use of these nutraceuticals. Most trials were on osteoarthritis of the knee, while virtually no documentation exists on spinal disc degeneration. The purpose of this article is to highlight the potential of these food additives against cartilage degeneration in general, and against symptomatic spinal disc degeneration in particular, as is illustrated by a case report. The water content of the intervertebral disc is a reliable measure of its degeneration/ regeneration status, and can be objectively determined by Magnetic Resonance Imaging (MRI) signals. Case presentation Oral intake of glucosamine and chondroitin sulfate for two years associated with disk recovery (brightening of MRI signal) in a case of symptomatic spinal disc degeneration. We provide a biochemical explanation for the possible efficacy of these nutraceuticals. They are bioavailable to cartilage chondrocytes, may stimulate the biosynthesis and inhibit the breakdown of their extracellular matrix proteoglycans. Conclusion The case suggests that long-term glucosamine and chondroitin sulfate intake may counteract symptomatic spinal disc degeneration, particularly at an early stage. However, definite proof requires well-conducted clinical trials with these food supplements, in which disc de-/regeneration can be objectively determined by MRI. A number of biochemical reasons (that mechanistically need to be further resolved) explain why these agents may have cartilage structure- and symptom-modifying effects, suggesting their therapeutic efficacy against osteoarthritis in general. PMID:12797867

  10. Pathology and possible mechanisms of nervous system response to disc degeneration.

    PubMed

    Brisby, Helena

    2006-04-01

    Degeneration of the intervertebral disc is clinically considered to be an important source of pain in patients with low-back pain. Disc deterioration and/or degeneration may influence the nervous system by stimulation of nociceptors in the anulus fibrosus, causing nociceptive pain that is often referred to as discogenic pain. The stimulation of the nociceptors may be of mechanical or inflammatory origin. Deterioration of a disc with loss of normal structure and weight-bearing properties may lead to abnormal motions that cause mechanical stimulation. This theory is supported by the fact that patients commonly experience an increase in pain with weight-bearing and certain movements. In addition, an ingrowth of vessels and nerve fibers into deeper layers of the anulus fibrosus has been observed in degenerated discs. A large number of inflammatory and signaling substances, such as tumor necrosis factor and interleukins (interleukin-1beta, interleukin-6, and interleukin-8), may also play a role in the development of back pain. Independent of stimulus of the nociceptors, the pain impulses are conducted through myelinated A delta fibers and unmyelinated C fibers to the dorsal root ganglion and continue by way of the spinothalamic tract to the thalamus and the somatosensory cortex. In response to stimulation of the nociceptors in the disc, the somatosensory system may increase its sensitivity, resulting in a nonfunctional response; that is, normally innocuous stimuli may generate an amplified response (peripheral sensitization). When disc degeneration leads to a disc herniation, the adjacent nervous system structures, such as the nerve roots or the dorsal root ganglion, can be affected, causing neuropathic pain of mechanical or biochemical origin. Disc deterioration also influences other spinal structures, such as facet joints, ligaments, and muscles, which can also become pain generators. Thus, disc degeneration may be responsible for the development of chronic low

  11. Organ culture bioreactors--platforms to study human intervertebral disc degeneration and regenerative therapy.

    PubMed

    Gantenbein, Benjamin; Illien-Jünger, Svenja; Chan, Samantha C W; Walser, Jochen; Haglund, Lisbet; Ferguson, Stephen J; Iatridis, James C; Grad, Sibylle

    2015-01-01

    In recent decades the application of bioreactors has revolutionized the concept of culturing tissues and organs that require mechanical loading. In intervertebral disc (IVD) research, collaborative efforts of biomedical engineering, biology and mechatronics have led to the innovation of new loading devices that can maintain viable IVD organ explants from large animals and human cadavers in precisely defined nutritional and mechanical environments over extended culture periods. Particularly in spine and IVD research, these organ culture models offer appealing alternatives, as large bipedal animal models with naturally occurring IVD degeneration and a genetic background similar to the human condition do not exist. Latest research has demonstrated important concepts including the potential of homing of mesenchymal stem cells to nutritionally or mechanically stressed IVDs, and the regenerative potential of "smart" biomaterials for nucleus pulposus or annulus fibrosus repair. In this review, we summarize the current knowledge about cell therapy, injection of cytokines and short peptides to rescue the degenerating IVD. We further stress that most bioreactor systems simplify the real in vivo conditions providing a useful proof of concept. Limitations are that certain aspects of the immune host response and pain assessments cannot be addressed with ex vivo systems. Coccygeal animal disc models are commonly used because of their availability and similarity to human IVDs. Although in vitro loading environments are not identical to the human in vivo situation, 3D ex vivo organ culture models of large animal coccygeal and human lumbar IVDs should be seen as valid alternatives for screening and feasibility testing to augment existing small animal, large animal, and human clinical trial experiments.

  12. Association Between Lumbar Spine Sagittal Alignment and L4-L5 Disc Degeneration Among Asymptomatic Young Adults.

    PubMed

    Menezes-Reis, Rafael; Bonugli, Gustavo Perazzoli; Dalto, Vitor Faeda; da Silva Herrero, Carlos Fernando Pereira; Defino, Helton Luiz Aparecido; Nogueira-Barbosa, Marcello Henrique

    2016-09-15

    Cross-sectional observational study on the relationship between the degrees of disc degeneration and sagittal alignment in asymptomatic healthy individuals. This study sought to determine whether the sagittal spine alignment subtype is related to the prevalence of lumbar disc degeneration. Sagittal balance and spinopelvic parameters might be risk factors for disc degeneration. A total of 70 asymptomatic participants (36 women and 34 men) without regular physical activity were categorized according to the four subtypes of sagittal alignment proposed by Roussouly. All participants underwent magnetic resonance imaging of the lumbar spine (1.5T) and panoramic radiography of the spine. The degree of disc degeneration was graded using T2-weighted images according to the Pfirrmann classification. Spinopelvic parameters and vertebral curvatures were measured on digital panoramic radiographs using Surgimap software. Interobserver analyses for the Pfirrmann classification and spinopelvic parameters were assessed using the weighted Kappa and intraclass correlation coefficient (ICC), respectively. The Kappa associated with disc degeneration classification was 0.79 (95% confidence intervals 0.72-0.87). The ICCs were excellent, with small confidence intervals for all spinopelvic parameters. The type II group (flat lordosis) showed a higher frequency of degenerated discs at L4-L5 (P = 0.03) than the type IV group (long and curved lumbar spine). No significant differences in disc degeneration were observed among the four subtypes at the other disc levels. We found a negative, moderate correlation between the spinopelvic parameters and the occurrence of disc degeneration in the type II group. The Roussouly subtype II sagittal alignment is significantly associated with disc degeneration at L4-L5 in asymptomatic young adults. Our results support the hypothesis that spinal sagittal alignment plays a role in early disc degeneration. 3.

  13. Herb formula "Fufangqishe-Pill" prevents upright posture-induced intervertebral disc degeneration at the lumbar in rats.

    PubMed

    Liang, Qian-Qian; Xi, Zhi-Jie; Bian, Qin; Cui, Xue-Jun; Li, Chen-Guang; Hou, Wei; Shi, Qi; Wang, Yong-Jun

    2010-01-01

    Degeneration of the lumbar spine plays an important role in most chronic low back pain. Prevention of lumbar intervertebral disc (IVD) degeneration is therefore a high research priority. Both our previous multicenter clinical trials and pharmacological research showed that Fufangqishe-Pill (FFQSP), a newly patented traditional Chinese medicine, could effectively relieve the symptoms of neck pain and prevent cervical degeneration. To clarify the effect of FFQSP on lumbar IVD degeneration, we applied a lumbar IVD degeneration rat model induced by prolonged upright posture. Pretreatment of FFQSP for one month prevented the histological changes indicating IVD disorganization; increased type II-collagen level, decreased type X-collagen protein level, and increased Col2alpha1 mRNA expression at all time points; and decreased Col10alpha1, matrix metalloproteinase (MMP)-3, MMP13, and Interleukin (IL)-1beta mRNA expression induced by upright posture for 7 and 9 months. These results suggest that FFQSP prevents lumbar IVD degeneration induced by upright posture. FFQSP is a promising medicine for lumbar IVD degeneration disease.

  14. Effects of unisegmental disc compression on adjacent segments: an in vivo animal model.

    PubMed

    Unglaub, Frank; Guehring, Thorsten; Lorenz, Helga; Carstens, Claus; Kroeber, Markus W

    2005-12-01

    It is controversial whether fusion of discs in the spine leads to increased degeneration on the remaining discs or whether the degenerative changes are merely a part of the inevitable natural history process. To determine the effects of unisegmental compression and subsequent recovery on adjacent segments, we studied histology, radiology and intradiscal pressure using an in vivo rabbit model. Fifteen New Zealand rabbits were divided in to three groups of five. In the first group, the intervertebral disc L4-L5 of the lumbar spine was axially loaded for 28 days with an external loading device. In the second group, the intervertebral disc was compressed for 28 days and allowed to recover for an equal amount of time, with the loading device removed. Five animals underwent a sham operation, in which the external loading device was situated, but their discs remained unloaded for 28 days. The intradiscal pressure was determined in the loaded discs as well as in the cranial and caudal adjacent discs. Lateral radiographs were taken from each subjected intervertebral disc with adjacent vertebral bodies and the cranial and caudal adjacent segments. The compressed discs showed lower intradiscal pressure in comparison with the control group, which remained unloaded. In the cranial and caudal discs adjacent to the loaded discs the average intradiscal pressure was similar to the unloaded controls. The loaded discs demonstrated a significant decrease in disc space. No discs adjacent to the loaded discs changed in height. The lamellar architecture of the inner, middle, and outer annulus became more disorganized in the loaded discs. The nucleus pulposus showed increase of mucoid degeneration and increased cell death. Intervertebral discs from the control group and the adjacent discs to the compressed discs maintained their normal morphology. This study shows that mechanical loading of discs in the spine can cause rapid degeneration. Adjacent discs, however, did not change in terms

  15. Correlation between T2∗ (T2 star) relaxation time and cervical intervertebral disc degeneration

    PubMed Central

    Huang, Minghua; Guo, Yong; Ye, Qiong; Chen, Lei; Zhou, Kai; Wang, Qingjun; Shao, Lixin; Shi, Qinglei; Chen, Chun

    2016-01-01

    Abstract Purpose: To demonstrate the potential benefits of T2∗ relaxation time of intervertebral discs (IVDs) regarding the detection and grading of degenerative disc disease using 3.0-T magnetic resonance imaging (MRI) in a clinical setting. Materials and Methods: Cervical sagittal T2-weighted, T2∗ relaxation MRI was performed at 3.0-T in 61 subjects, covering discs C2–3 to C6–7. All discs were morphologically assessed based on the Pfirrmann grade, and regions of interests (ROIs) were drawn over the T2∗ mapping. Receiver operating characteristic (ROC) analysis was performed among grades to determine the cut-off values. Results: Cervical intervertebral discs (IVDs) of patients were commonly determined to be at Pfirrmann grades III to V. The nucleus pulposus (NP) values did not differ significantly between sexes at the same anatomic level (P > 0.05). In the NP, the T2∗ values tended to decrease with increasing grade (P < 0.000), and a significant difference was found in the T2 values between grades I to V (P < 0.05). T2∗ values based on disc degeneration level classification were as follows: grade I (>30 milliseconds), grade II (24.55–29.99 milliseconds), grade III (21.65–24.54 milliseconds), grade IV (18.35–21.64 milliseconds), and grade V (<18.34 milliseconds). Conclusion: Our standardized method of region-specific quantitative T2∗ relaxation time evaluation seems capable of characterizing different degrees of disc degeneration quantitatively. The T2∗ values obtained in these cervical IVDs may serve as baseline values for future T2∗ measurements in both healthy and degenerated cervical discs. PMID:27893652

  16. Degenerate Hopf bifurcation in a self-exciting Faraday disc dynamo

    NASA Astrophysics Data System (ADS)

    Pan, Weiquan; Li, Lijie

    2017-06-01

    In order to further understand a self-exciting Faraday disc dynamo (Hide et al, in Proc. R. Soc. A 452, 1369 1996), showing chaotic attractors with very complicated topological structures, we present codimension one and two (degenerate) Hopf bifurcations and prove the existence of periodic solutions. In addition, numerical simulations are given for confirming the theoretical results.

  17. L5-S1 disc degeneration and the anatomic parameters of the iliac crest: imaging study.

    PubMed

    Wang, Yong-Li; Wang, Xiang-Yang; Fang, Bi-Dong; Chi, Yong-Long; Xu, Hua-Zi; Wu, Li-Jun; Lin, Zhong-Ke

    2015-11-01

    To evaluate the relationship between height ratio of the iliac crest to L4 (HR), width ratio of the iliac crest to L4 (WR) and L5-S1 disc degeneration. On T2-weighted sagittal images of the 50 randomly selected patients, two observers graded L5-S1 discs and some other parameters were measured. Then, relative signal intensity (RSI) of the L5-S1 nucleus pulposus was calculated. On anteroposterior and lateral radiographs of the same 50 patients' lumbar spine, the parameters such as the height of the iliac crest were measured and then HR and WR were calculated. Finally, HR, WR and the percentage of the sROM of L5-S1 in L1-S1 segments of the other 51 randomly selected patients were calculated. Positive correlations were found between HR, WR and RSI of the L5-S1 disc. Negative correlations were found between HR, WR and modified Pfirrmann scores of L5-S1 nucleus pulposus. A statistically significant negative correlation was found between HR and the percentage of sROM of L5-S1 in L1-S1 segments. Low HR and (or) WR were the risk factors for L5-S1 disc degeneration. High HR could reduce the percentage of sROM of L5-S1 in L1-S1 segments and high HR and (or) WR could reduce the incidence of L5-S1 disc degeneration.

  18. Endplate degeneration may be the origination of the vacuum phenomenon in intervertebral discs.

    PubMed

    Li, Fang-Cai; Zhang, Ning; Chen, Wei-Shan; Chen, Qi-Xin

    2010-08-01

    The intravertebral vacuum phenomenon (VP) is usually associated with degenerative disc disease, which could be related to the low back pain. Various theories related to the pathogenesis of VP have been proposed, but these theories have not been critically examined and remain hypothetical. In this article, we review the possible role of endplate degeneration in the pathogenesis of VP, and discuss several pathways possibly linked to them. Due to the endplate calcification and activated cytokines, the transport pathway of the nutrition for the intervertebral disc was blocked, resulting in the metabolic unbalance and decrease of the synthesis of matrix structural proteins. It could promote the matrix decomposition, causing the decrease of the quantity of matrix and the changes of stress distribution in intervertebral disc. As a result, the structure of intervertebral discs became increasingly unstable. While compression happened, the intravertebral cleft could occur and be gradually filled with gas, which may cause low back pain and aggravate the intervertebral discs degeneration. As outlined above, we hypothesize that endplate degeneration might be the origination of the vacuum phenomenon.

  19. Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF in a rat model.

    PubMed

    Hu, Yuan; Tang, Jin-Shu; Hou, Shu-Xun; Shi, Xiu-Xiu; Qin, Jiang; Zhang, Tie-Song; Wang, Xiao-Jing

    2017-09-12

    Curcumin is a natural product with antimutagenic, antitumor, antioxidant and neuroprotective properties. However, to the best of our knowledge, curcumin has yet to be investigated for the treatment of lumbar intervertebral disc degeneration LIDD). The aim of the present study was to investigate whether curcumin can alleviate LIDD through regulating the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‑2, transforming growth factor (TGF)‑β1/2, matrix metalloproteinase (MMP)‑9 and brain‑derived neurotrophic factor (BDNF) in a rat model of LIDD. The results of the present study suggest that pretreatment with curcumin can prevent the development of LIDD in rats. It was revealed that treatment with curcumin significantly reduced interleukin (IL)‑1β and IL‑6, iNOS, COX‑2 and MMP‑9 levels in rats with LIDD. In addition, treatment with curcumin reduced the mRNA expression levels of TGF‑β1 and TGF‑β2, whereas it increased the mRNA expression levels of BDNF in rats with LIDD. In conclusion, the present findings indicate that curcumin may exert protective effects on LIDD development, exerting its action through the regulation of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF.

  20. Hydrogen sulfide protects against endoplasmic reticulum stress and mitochondrial injury in nucleus pulposus cells and ameliorates intervertebral disc degeneration.

    PubMed

    Xu, Daoliang; Jin, Haiming; Wen, Jianxia; Chen, Jiaoxiang; Chen, Deheng; Cai, Ningyu; Wang, Yongli; Wang, Jianle; Chen, Yu; Zhang, Xiaolei; Wang, Xiangyang

    2017-03-01

    It has been suggested that excessive apoptosis in intervertebral disc cells induced by inflammatory cytokines, such as interleukin (IL)-1β, is related to the process of intervertebral disc degeneration (IVDD). Hydrogen sulfide (H2S), a gaseous signaling molecule, has drawn attention for its anti-apoptosis role in various pathophysiological processes in degenerative diseases. To date, there has been no investigation of the correlation of H2S production and IVDD or of the effects of H2S on IL-1β-induced apoptosis in nucleus pulposus (NP) cells. Here, we found that the expression levels of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), two key enzymes in the generation of H2S, were significantly decreased in human degenerate NP tissues as well as in IL-1β-treated NP cells. NaHS (H2S donor) administration showed a protective effect by inhibiting the endoplasmic reticulum (ER) stress response and mitochondrial dysfunction induced by IL-1β stimulation in vitro, the effect was related to activation of the PI3K/Akt and ERK1/2 signaling pathways. Suppression of these pathways by specific inhibitors, LY294002 and PD98059, partially reduced the protective effect of NaHS. Moreover, in the percutaneous needle puncture disc degeneration rat tail model, disc degeneration was partially reversed by NaHS administration. Taken together, our results suggest that H2S plays a protective role in IVDD and the underlying mechanism involves PI3K/Akt and ERK1/2 signaling pathways-mediated suppression of ER stress and mitochondrial dysfunction in IL-1β-induced NP cells.

  1. Longitudinal Comparison of Enzyme- and Laser-Treated Intervertebral Disc by MRI, X-Ray, and Histological Analyses Reveals Discrepancies in the Progression of Disc Degeneration: A Rabbit Study

    PubMed Central

    Colombier, Pauline; Lesoeur, Julie; Youl, Samy; Madec, Stéphane; Gauthier, Olivier; Hamel, Olivier; Guicheux, Jérôme; Clouet, Johann

    2016-01-01

    Regenerative medicine is considered an attractive prospect for the treatment of intervertebral disc (IVD) degeneration. To assess the efficacy of the regenerative approach, animal models of IVD degeneration are needed. Among these animal models, chemonucleolysis based on the enzymatic degradation of the Nucleus Pulposus (NP) is often used, but this technique remains far from the natural physiopathological process of IVD degeneration. Recently, we developed an innovative animal model of IVD degeneration based on the use of a laser beam. In the present study, this laser model was compared with the chemonucleolysis model in a longitudinal study in rabbits. The effects of the treatments were studied by MRI (T2-weighted signal intensity (T2wsi)), radiography (IVD height index), and histology (NP area and Boos' scoring). The results showed that both treatments induced a degeneration of the IVD with a decrease in IVD height and T2wsi as well as NP area and an increase in Boos' scoring. The enzyme treatment leads to a rapid and acute process of IVD degeneration. Conversely, laser radiation induced more progressive and less pronounced degeneration. It can be concluded that laser treatment provides an instrumental in vivo model of slowly evolving IVD degenerative disease that can be of preclinical relevance for assessing new prophylactic biological treatments of disc degeneration. PMID:27247937

  2. Automated grading of lumbar disc degeneration via supervised distance metric learning

    NASA Astrophysics Data System (ADS)

    He, Xiaoxu; Landis, Mark; Leung, Stephanie; Warrington, James; Shmuilovich, Olga; Li, Shuo

    2017-03-01

    Lumbar disc degeneration (LDD) is a commonly age-associated condition related to low back pain, while its consequences are responsible for over 90% of spine surgical procedures. In clinical practice, grading of LDD by inspecting MRI is a necessary step to make a suitable treatment plan. This step purely relies on physicians manual inspection so that it brings the unbearable tediousness and inefficiency. An automated method for grading of LDD is highly desirable. However, the technical implementation faces a big challenge from class ambiguity, which is typical in medical image classification problems with a large number of classes. This typical challenge is derived from the complexity and diversity of medical images, which lead to a serious class overlapping and brings a great challenge in discriminating different classes. To solve this problem, we proposed an automated grading approach, which is based on supervised distance metric learning to classify the input discs into four class labels (0: normal, 1: slight, 2: marked, 3: severe). By learning distance metrics from labeled instances, an optimal distance metric is modeled and with two attractive advantages: (1) keeps images from the same classes close, and (2) keeps images from different classes far apart. The experiments, performed in 93 subjects, demonstrated the superiority of our method with accuracy 0.9226, sensitivity 0.9655, specificity 0.9083, F-score 0.8615. With our approach, physicians will be free from the tediousness and patients will be provided an effective treatment.

  3. Development of an intact intervertebral disc organ culture system in which degeneration can be induced as a prelude to studying repair potential.

    PubMed

    Jim, Bernice; Steffen, Thomas; Moir, Janet; Roughley, Peter; Haglund, Lisbet

    2011-08-01

    The present work describes a novel bovine disc organ culture system with long-term maintenance of cell viability, in which degenerative changes can be induced as a prelude to studying repair. Discs were isolated with three different techniques: without endplates (NEP), with bony endplates (BEP) and with intact cartilage endplates (CEP). Swelling, deformation, and cell viability were evaluated in unloaded cultures. Degeneration was induced by a single trypsin injection into the center of the disc and the effect on cell viability and matrix degradation was followed. Trypsin-treated discs were exposed to TGFβ to evaluate the potential to study repair in this system. NEP isolated discs showed >75% maintained cell viability for up to 10 days but were severely deformed, BEP discs on the other hand maintained morphology but failed to retain cell viability having only 27% viable cells after 10 days. In CEP discs, both cell viability and morphology were maintained for at least 4 weeks where >75% of the cells were still viable. To mimic proteoglycan loss during disc degeneration, a single trypsin injection was administered to the center of the disc. This resulted in 60% loss of aggrecan, after 7 days, without affecting cell viability. When TGFβ was injected to validate that the system can be used to study a repair response following injection of a bio-active substance, proteoglycan synthesis nearly doubled compared to baseline synthesis. Trypsin-treated bovine CEP discs therefore provide a model system for studying repair of the degenerate disc, as morphology, cell viability and responsiveness to bio-active substances were maintained.

  4. Lack of association between lumbar disc degeneration and osteophyte formation in elderly japanese women with back pain.

    PubMed

    Oishi, Y; Shimizu, K; Katoh, T; Nakao, H; Yamaura, M; Furuko, T; Narusawa, K; Nakamura, T

    2003-04-01

    Our study was designed to assess the contributions of the physical and constitutional factors to osteophyte formation, disc degeneration, and bone mineral density (BMD) in lumbar vertebrae of elderly postmenopausal women. A total of 126 Japanese women with back pain, aged over 60 years, were invited to participate in the study. Then 80 subjects with a full set of data for physical examinations, radiographs, MRI, and DXA were examined. TaqI polymorphism of vitamin D receptor (VDR) gene was examined in 60 subjects. Prevalence rates of osteophytes (on radiographs) and disc degeneration (on MRI) were 61 and 68%, respectively. Body weight and BMI correlated significantly with anteroposterior (AP) and lateral (LAT) BMD (r = 0.354 for weight, r = 0.347 for BMI) and mean osteophyte area (r = 0.557 for weight, r = 0.486 for BMI), and body weight also correlated with number of discs with osteophytes. However, these did not correlate with the disc area or the number of degenerated discs. Stepwise regression analysis revealed that body weight and LAT-BMD values independently related to the osteophyte area. Disc area (r = 0.386 for AP view) and osteophyte area (r = 0.384 for AP view) significantly correlated with BMD. However, disc area and osteophyte area did not correlate with each other (r = 0.056). The proportion of degenerated discs was higher in the lower lumbar discs, but not the proportion of discs with osteophytes. Frequencies of T and t alleles of VDR did not correlate with disc degeneration, osteophyte formation, or osteoporosis. Our data showed that increases in osteophyte formation and BMD in the lumbar vertebrae are influenced by body weight and BMI, but did not correlate with disc area, which correlated inversely with BMD. Disc degeneration and osteophyte formation seem to represent two different factors that affect lumbar spine in elderly women.

  5. Disc Degeneration Assessed by Quantitative T2* (T2 star) Correlated with Functional Lumbar Mechanics

    PubMed Central

    Ellingson, Arin M.; Mehta, Hitesh; Polly, David W.; Ellermann, Jutta; Nuckley, David J.

    2013-01-01

    Study Design Experimental correlation study design to quantify features of disc health, including signal intensity and distinction between the annulus fibrosus (AF) and nucleus pulposus (NP), with T2* magnetic resonance imaging (MRI) and correlate with the functional mechanics in corresponding motion segments. Objective Establish the relationship between disc health assessed by quantitative T2* MRI and functional lumbar mechanics. Summary of Background Data Degeneration leads to altered biochemistry in the disc, affecting the mechanical competence. Clinical routine MRI sequences are not adequate in detecting early changes in degeneration and fails to correlate with pain or improve patient stratification. Quantitative T2* relaxation time mapping probes biochemical features and may offer more sensitivity in assessing disc degeneration. Methods Cadaveric lumbar spines were imaged using quantitative T2* mapping, as well as conventional T2-weighted MRI sequences. Discs were graded by the Pfirrmann scale and features of disc health, including signal intensity (T2* Intensity Area) and distinction between the AF and NP (Transition Zone Slope), were quantified by T2*. Each motion segment was subjected to pure moment bending to determine range of motion (ROM), neutral zone (NZ), and bending stiffness. Results T2* Intensity Area and Transition Zone Slope were significantly correlated with flexion ROM (p=0.015; p=0.002), ratio of NZ/ROM (p=0.010; p=0.028), and stiffness (p=0.044; p=0.026), as well as lateral bending NZ/ROM (p=0.005; p=0.010) and stiffness (p=0.022; p=0.029). T2* Intensity Area was also correlated with LB ROM (p=0.023). Pfirrmann grade was only correlated with lateral bending NZ/ROM (p=0.001) and stiffness (p=0.007). Conclusions T2* mapping is a sensitive quantitative method capable of detecting changes associated with disc degeneration. Features of disc health quantified with T2* predicted altered functional mechanics of the lumbar spine better than

  6. The Effects of Platelet-Rich Plasma on Halting the Progression in Porcine Intervertebral Disc Degeneration.

    PubMed

    Cho, Hongsik; Holt, David C; Smith, Richard; Kim, Song-Ja; Gardocki, Raymond J; Hasty, Karen A

    2016-02-01

    Disc degeneration and the subsequent herniation and/or rupture of the intervertebral disc (IVD) are due to a failure of the extracellular matrix of the annulus to contain the contents of the nucleus. This results from inadequate maintenance of the matrix components as well as the proteolytic activity of matrix metalloproteinases (MMPs) that degrade matrix molecules. Arresting progression of disc degeneration in the annulus holds greater clinical potential at this point than prevention of its onset in the nucleus. Therefore, in this study, we have therapeutic aims that would decrease levels of the cytokines and growth factors that indirectly lead to disc degeneration via stimulating MMP and increase levels of several beneficial growth factors, such as transforming growth factor-β, with the addition of platelet-rich plasma (PRP) that would stimulate cell growth and matrix synthesis. For this study, we attempted to address these imbalances of metabolism by using tumor necrosis factor-α treated annulus fibrosus cells isolated from porcine IVD tissue and incubating the cells in a growth factor rich environment with PRP. These results indicate that the PRP in vitro increased the production of the major matrix components (type II collagen and aggrecan) and decreased the inhibitory collagenase MMP-1. This application will address a therapeutic approach for intervening early in the degenerative process.

  7. Structured bilaminar co-culture outperforms stem cells and disc cells in a simulated degenerate disc environment

    PubMed Central

    Allon, Aliza A.; Butcher, Kristin; Schneider, Richard A.; Lotz, Jeffrey C.

    2011-01-01

    Study Design This study explores the use of bilaminar coculture pellets of mesenchymal stem cells (MSC) and Nucleus Pulposus cells (NPC) as a cell-based therapy for intervertebral disc regeneration. The pellets were tested under conditions that mimic the degenerative disc. Objective Our goal is to optimize our cell-based therapy in vitro under conditions representative of the eventual diseased tissue. Summary of Background Data Harnessing the potential of stem cells is an important strategy for regenerative medicine. Our approach seeks to direct the behavior of stem cells by mimicking embryonic processes underlying cartilage and intervertebral disc development. Prior experiments have shown that bilaminar co-culture can help differentiate MSC and substantially improve new matrix deposition. Methods We have designed a novel spherical bilaminar cell pellet (BCP) where MSC are enclosed in a shell of NPC. There were three groups: MSC, NPC, and BCP. The pellets were tested under three different culture conditions: in a bioreactor that provides pressure & hypoxia (mimicking normal disc conditions), with inflammatory cytokines (IL-1b and TNF-a), and a bioreactor with inflammation (mimicking painful disc conditions). Results When cultured in the bioreactor, the NPC pellets produced significantly more glycosaminoglycan (GAG)/cell than the other groups: 70-80% more than the BCP and MSC alone. When cultured in an inflammatory environment, the MSC and BCP groups produced 30-34% more GAG/cell than NPC (p<0.05). When the pellets were cultured in a bioreactor with inflammation, the BCP made 25% more GAG/cell than MSC and 57% more than NPC (p<0.05). Conclusion This study shows that BCP outperform controls in a simulated degenerated disc environment. Adapting inductive mechanisms from development to trigger differentiation and restore diseased tissue has many advantages. As opposed to strategies that require growth factor supplements or genetic manipulations, our method is self

  8. Reliable Magnetic Resonance Imaging Based Grading System for Cervical Intervertebral Disc Degeneration

    PubMed Central

    Chen, Antonia F.; Kang, James D.; Lee, Joon Y.

    2016-01-01

    Study Design Observational. Purpose To develop a simple and comprehensive grading system for cervical discs that precisely, consistently and meaningfully presents radiologic and morphologic data. Overview of Literature The Thompson grading system is commonly used to classify the severity of degenerative lumbar discs on magnetic resonance imaging (MRI). Inherent differences in the morphological and physiological characteristics of cervical discs have hindered development of precise classification systems. Other grading systems have been developed for degenerating cervical discs, but their versatility and feasibility in the clinical setting is suboptimal. Methods MRIs of 46 human cervical discs were de-identified and displayed in PowerPoint format. Each slide depicted a single disc with a normal (grade 0) disc displayed in the top right corner for reference. The presentation was given to 25 physicians comprising attending spine surgeons, spine fellows, orthopaedic residents, and two attending musculoskeletal radiologists. The grading system included Grade 0 (normal height compared to C2–3, mid cleft still visible), grade 1 (dark disc, normal height), grade 2 (collapsed disc, few osteophytes), and grade 3 (collapsed disc, many osteophytes). The ease of use of the system was gauged in the participants and the interobserver reliability was calculated. Results The intraclass correlation coefficient for interobserver reliability was 0.87, and 0.94 for intraobserver reliability, indicating excellent reliability. Ninety-five percent and 85 percent of the clinicians judged the grading system to be clinically feasible and useful in daily practice, respectively. Conclusions The grading system is easy to use, has excellent reliability, and can be used for precise and consistent clinician communication. PMID:26949461

  9. 1991 Volvo Award in clinical sciences. Smoking and lumbar intervertebral disc degeneration: an MRI study of identical twins.

    PubMed

    Battié, M C; Videman, T; Gill, K; Moneta, G B; Nyman, R; Kaprio, J; Koskenvuo, M

    1991-09-01

    The primary objective of this study was to determine whether disc degeneration, as assessed through magnetic resonance imaging, is greater in smokers than in nonsmokers. To control for the maximum number of potentially confounding variables, pairs of identical twins highly discordant for cigarette smoking were selected as study subjects. Data analyses revealed 18% greater mean disc degeneration scores in the lumbar spines of smokers as compared with nonsmokers. The effect was present across the entire lumbar spine, implicating a mechanism acting systemically. This investigation demonstrates the efficiency of using carefully selected controls in studying conditions of multifactorial etiology, such as disc degeneration.

  10. A role for TNFα in intervertebral disc degeneration: A non-recoverable catabolic shift

    SciTech Connect

    Purmessur, D.; Walter, B.A.; Roughley, P.J.; Laudier, D.M.; Hecht, A.C.; Iatridis, James

    2013-03-29

    Highlights: ► TNFα induced catabolic changes similar to human intervertebral disc degeneration. ► The metabolic shift induced by TNFα was sustained following removal. ► TNFα induced changes suggestive of cell senescence without affecting cell viability. ► Interventions are required to stimulate anabolism and increase cell proliferation. -- Abstract: This study examines the effect of TNFα on whole bovine intervertebral discs in organ culture and its association with changes characteristic of intervertebral disc degeneration (IDD) in order to inform future treatments to mitigate the chronic inflammatory state commonly found with painful IDD. Pro-inflammatory cytokines such as TNFα contribute to disc pathology and are implicated in the catabolic phenotype associated with painful IDD. Whole bovine discs were cultured to examine cellular (anabolic/catabolic gene expression, cell viability and senescence using β-galactosidase) and structural (histology and aggrecan degradation) changes in response to TNFα treatment. Control or TNFα cultures were assessed at 7 and 21 days; the 21 day group also included a recovery group with 7 days TNFα followed by 14 days in basal media. TNFα induced catabolic and anti-anabolic shifts in the nucleus pulposus (NP) and annulus fibrosus (AF) at 7 days and this persisted until 21 days however cell viability was not affected. Data indicates that TNFα increased aggrecan degradation products and suggests increased β-galactosidase staining at 21 days without any recovery. TNFα treatment of whole bovine discs for 7 days induced changes similar to the degeneration processes that occur in human IDD: aggrecan degradation, increased catabolism, pro-inflammatory cytokines and nerve growth factor expression. TNFα significantly reduced anabolism in cultured IVDs and a possible mechanism may be associated with cell senescence. Results therefore suggest that successful treatments must promote anabolism and cell proliferation in

  11. Ultrastructure of inclusion bodies in annulus cells in the degenerating human intervertebral disc.

    PubMed

    Gruber, H E; Hanley, E N

    2009-06-01

    The rough endoplasmic reticulum (rER) of the cell has an architectural editing function that checks whether protein structure and three-dimensional assembly have occurred properly prior to export of newly synthesized material out of the cell. If these have been faulty, the material is retained within the rER as an inclusion body. Inclusion bodies have been identified previously in chondrocytes and osteoblasts in chondrodysplasias and osteogenesis imperfecta. Inclusion bodies in intervertebral disc cells, however, have only recently been recognized. Our objectives were to use transmission electron microscopy to analyze more fully inclusion bodies in the annulus pulposus and to study the extracellular matrix (ECM) surrounding cells containing inclusion bodies. ECM frequently encapsulated cells with inclusion bodies, and commonly contained prominent banded aggregates of Type VI collagen. Inclusion body material had several morphologies, including relatively smooth, homogeneous material, or a rougher, less homogeneous feature. Such findings expand our knowledge of the fine structure of the human disc cell and ECM during disc degeneration, and indicate the potential utility of ultrastructural identification of discs with intracellular inclusion bodies as a screening method for molecular studies directed toward identification of defective gene products in degenerating discs.

  12. Intradiscal pressure measurements in normal discs, compressed discs and compressed discs treated with axial posterior disc distraction: an experimental study on the rabbit lumbar spine model.

    PubMed

    Guehring, Thorsten; Unglaub, Frank; Lorenz, Helga; Omlor, Georg; Wilke, Hans-Joachim; Kroeber, Markus W

    2006-05-01

    Intervertebral disc (IVD) pressure measurement is an appropriate method for characterizing spinal loading conditions. However, there is no human or animal model that provides sufficient IVD pressure data. The aim of our study was to establish physiological pressure values in the rabbit lumbar spine and to determine whether temporary external disc compression and distraction were associated with pressure changes. Measurements were done using a microstructure-based fibreoptic sensor. Data were collected in five control rabbits (N, measurement lying prone at segment L3/4 at day 28), five rabbits with 28 days of axial compression (C, measurement at day 28) and three rabbits with 28 days of axial compression and following 28 days of axial distraction (D, measurement at day 56). Disc compression and distraction was verified by disc height in lateral radiographs. The controls (N) showed a level-related range between 0.25 MPa-0.45 MPa. The IVD pressure was highest at level L3/4 (0.42 MPa; range 0.38-0.45) with a decrease in both cranial and caudal adjacent segments. The result for C was a significant decrease in IVD pressure (0.31 MPa) when compared with controls (P=0.009). D showed slightly higher median IVD pressure (0.32 MPa) compared to C, but significantly lower levels when compared with N (P=0.037). Our results indicate a high range of physiological IVD pressure at different levels of the lumbar rabbit spine. Temporary disc compression reduces pressure when compared with controls. These data support the hypothesis that temporary external compression leads to moderate disc degeneration as a result of degradation of water-binding disc matrix or affected active pumping mechanisms of nutrients into the disc. A stabilization of IVD pressure in discs treated with temporary distraction was observed.

  13. The intervertebral disc contains intrinsic circadian clocks that are regulated by age and cytokines and linked to degeneration

    PubMed Central

    Dudek, Michal; Yang, Nan; Ruckshanthi, Jayalath PD; Williams, Jack; Borysiewicz, Elzbieta; Wang, Ping; Adamson, Antony; Li, Jian; Bateman, John F; White, Michael R; Boot-Handford, Raymond P; Hoyland, Judith A; Meng, Qing-Jun

    2017-01-01

    Objectives The circadian clocks are internal timing mechanisms that drive ∼24-hour rhythms in a tissue-specific manner. Many aspects of the physiology of the intervertebral disc (IVD) show clear diurnal rhythms. However, it is unknown whether IVD tissue contains functional circadian clocks and if so, how their dysregulation is implicated in IVD degeneration. Methods Clock gene dynamics in ex vivo IVD explants (from PER2:: luciferase (LUC) reporter mice) and human disc cells (transduced with lentivirus containing Per2::luc reporters) were monitored in real time by bioluminescence photon counting and imaging. Temporal gene expression changes were studied by RNAseq and quantitative reverse transcription (qRT)-PCR. IVD pathology was evaluated by histology in a mouse model with tissue-specific deletion of the core clock gene Bmal1. Results Here we show the existence of the circadian rhythm in mouse IVD tissue and human disc cells. This rhythm is dampened with ageing in mice and can be abolished by treatment with interleukin-1β but not tumour necrosis factor α. Time-series RNAseq revealed 607 genes with 24-hour patterns of expression representing several essential pathways in IVD physiology. Mice with conditional knockout of Bmal1 in their disc cells demonstrated age-related degeneration of IVDs. Conclusions We have established autonomous circadian clocks in mouse and human IVD cells which respond to age and cytokines, and control key pathways involved in the homeostasis of IVDs. Genetic disruption to the mouse IVD molecular clock predisposes to IVD degeneration. These results support the concept that disruptions to circadian rhythms may be a risk factor for degenerative IVD disease and low back pain. PMID:27489225

  14. Degeneration of the intervertebral disc with new approaches for treating low back pain.

    PubMed

    Le Maitre, C L; Binch, A L; Thorpe, A A; Hughes, S P

    2015-03-01

    This review paper discusses the process of disc degeneration and the current understanding of cellular degradation in patients who present with low back pain. The role of surgical treatment for low back pain is analysed with emphasis on the proven value of spinal fusion. The interesting and novel developments of stem cell research in the treatment of low back pain are presented with special emphasis on the importance of the cartilaginous end plate and the role of IL-1 in future treatment modalities.

  15. Early UV emission from disc-originated matter (DOM) in Type Ia supernovae in the double-degenerate scenario

    NASA Astrophysics Data System (ADS)

    Levanon, Naveh; Soker, Noam

    2017-09-01

    We show that the blue and UV excess emission in the first few days of some Type Ia supernovae (SNe Ia) can be accounted in the double-degenerate (DD) scenario by the collision of the SN ejecta with circumstellar matter that was blown by the accretion disc formed during the merger process of the two white dwarfs (WDs). We assume that in cases of excess early light, the disc blows the circumstellar matter, that we term disc-originated matter (DOM), hours to days before explosion. To perform our analysis, we first provide a model-based definition for early excess light, replacing the definition of excess light relative to a power-law fit to the rising luminosity. We then examine the light curves of the SNe Ia iPTF14atg and SN 2012cg, and find that the collision of the ejecta with a DOM in the frame of the DD scenario can account for their early excess emission. Thus, early excess light does not necessarily imply the presence of a stellar companion in the frame of the single-degenerate scenario. Our findings further increase the variety of phenomena that the DD scenario can account for, and emphasize the need to consider all different SN Ia scenarios when interpreting observations.

  16. Identifying molecular phenotype of nucleus pulposus cells in human intervertebral disc with aging and degeneration.

    PubMed

    Tang, Xinyan; Jing, Liufang; Richardson, William J; Isaacs, Robert E; Fitch, Robert D; Brown, Christopher R; Erickson, Melissa M; Setton, Lori A; Chen, Jun

    2016-08-01

    Previous study claimed that disc degeneration may be preceded by structure and matrix changes in the intervertebral disc (IVD) which coincide with the loss of distinct notochordally derived nucleus pulposus (NP) cells. However, the fate of notochordal cells and their molecular phenotype change during aging and degeneration in human are still unknown. In this study, a set of novel molecular phenotype markers of notochordal NP cells during aging and degeneration in human IVD tissue were revealed with immunostaining and flow cytometry. Furthermore, the potential of phenotype juvenilization and matrix regeneration of IVD cells in a laminin-rich pseudo-3D culture system were evaluated at day 28 by immunostaining, Safranin O, and type II collagen staining. Immunostaining and flow cytometry demonstrated that transcriptional factor Brachyury T, neuronal-related proteins (brain abundant membrane attached signal protein 1, Basp1; Neurochondrin, Ncdn; Neuropilin, Nrp-1), CD24, and CD221 were expressed only in juvenile human NP tissue, which suggested that these proteins may be served as the notochordal NP cell markers. However, the increased expression of CD54 and CD166 with aging indicated that they might be referenced as the potential biomarker for disc degeneration. In addition, 3D culture maintained most of markers in juvenile NP, and rescued the expression of Basp1, Ncdn, and Nrp 1 that disappeared in adult NP native tissue. These findings provided new insight into molecular profile that may be used to characterize the existence of a unique notochordal NP cells during aging and degeneration in human IVD cells, which will facilitate cell-based therapy for IVD regeneration. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1316-1326, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  17. MRI methodological development of intervertebral disc degeneration: a rabbit in vivo study at 9.4 T.

    PubMed

    Noury, Fanny; Mispelter, Joël; Szeremeta, Frédéric; Même, Sandra; Doan, Bich-Thuy; Beloeil, Jean-Claude

    2008-12-01

    Intervertebral disc (IVD) degeneration is a complex process characterized by biochemical and structural changes in both the nucleus pulposus and the anulus fibrosus. In this study, we were able to obtain in vivo magnetic resonance (MR) images of the rabbit spine, with several MR imaging (MRI) contrasts (rho, T(1) and T(2)). We quantified several parameters (T(2), apparent diffusion coefficient, disc height and area) to differentiate between healthy and degenerative IVDs and to characterize the degeneration process. To our knowledge, there has not been any previous in vivo study of rabbit IVDs at high-field MRI (9.4 T). A custom radio frequency (RF) coil for 9.4 T was designed to match rabbit IVD morphology, to study the degeneration in vivo on a model of human lumbar disease. Our new probe, a custom half-birdcage-type coil, obtains the necessary exploration depth while meeting the requirements for signal homogeneity and sensitivity of the study. This design addresses some of the difficulties with constructing RF coils at high field strengths.

  18. Effects of psoralen on chondrocyte degeneration in lumbar intervertebral disc of rats.

    PubMed

    Yang, Libin; Sun, Xiaohui; Geng, Xiaolin

    2015-03-01

    Discuss the internal mechanism of delaying degeneration of lumber intervertebral disc. The cartilage of lumbar intervertebral disc of SD rats was selected in vitro, then cultured by tissue explant method, and identified by HE staining, toluidine blue staining and immunofluorescence. The optimal concentration of psoralen was screened by cell proliferation assay and RT-PCR method. The cells in third generation with good growth situation is selected and placed in 6-well plate at concentration of 1×10(5)/well and its expression was tested. Compared to concentration of 0, the mRNA expression of Col2al (Collagen Ⅱ) secreted by was up regulated chondrocyte of lumbar intervertebral disc at the concentration of 12.5 and 25μM (P<0.0 or P<0.01). The aggrecan mRNA of psoralen group was higher than blank control group (P<0.01); compared with IL-1β induced group, the mRNA expression of Col2al was significantly increased but the mRNA expression of ADAMTS-5 was significantly decreased in psoralen group (P<0.01). These findings suggest that, psoralen can remit the degeneration of lumbar intervertebral disc induced by IL-1β to some extent, and affect the related factors of IL-1β signaling pathway.

  19. MSC response to pH levels found in degenerating intervertebral discs

    SciTech Connect

    Wuertz, Karin Godburn, Karolyn; Iatridis, James C.

    2009-02-20

    Painful degenerative disc disease is a major health problem and for successful tissue regeneration, MSCs must endure and thrive in a harsh disc microenvironment that includes matrix acidity as a critical factor. MSCs were isolated from bone marrow of Sprague-Dawley rats from two different age groups (<1 month, n = 6 and 4-5 months, n = 6) and cultured under four different pH conditions representative of the healthy, mildly or severely degenerated intervertebral disc (pH 7.4, 7.1, 6.8, and 6.5) for 5 days. Acidity caused an inhibition of aggrecan, collagen-1, and TIMP-3 expression, as well as a decrease in proliferation and viability and was associated with a change in cell morphology. Ageing had generally minor effects but young MSCs maintained greater mRNA expression levels. As acidic pH levels are typical of increasingly degenerated discs, our findings demonstrate the importance of early interventions and predifferentiation when planning to use MSCs for reparative treatments.

  20. Correlation of end plate shape on MRI and disc degeneration in surgically treated patients with degenerative disc disease and herniated nucleus pulposus.

    PubMed

    Pappou, Ioannis P; Cammisa, Frank P; Girardi, Federico P

    2007-01-01

    The sagittal profile of the lumbar end plates on magnetic resonance imaging (MRI) has not been investigated in patients with degenerative disc disease (DDD) or herniated nucleus pulposus (HNP). To examine the shape of the end plates in patients treated surgically for a) low back pain or b) radiculopathy with HNP. Furthermore, to investigate the correlation between end plate shape and disc degeneration on the one, and end plate shape and symptoms on the other. Retrospective review of charts and radiographs. The charts, operative reports, preoperative lateral plain radiographs, and MRI scans of 178 patients (85 with low back pain and 93 with HNP) were reviewed. End plate shape was determined on midsagittal MRI cuts, disc degeneration was graded on T2 sequences, and disc height was measured on lateral plain radiographs from L1 to S1 in all patients. Student t-test and chi(2) test were used to detect significant differences and associations. Flat and irregular levels were most common in the lower lumbar spine. The L5/S1 segment was flat in most cases, due to a flat sacral end plate. In DDD patients, disc degeneration on MRI and plain radiographs worsened from concave to flat, to irregular levels. In HNP patients, MRI demonstrated concave levels to be less degenerated, whereas no difference was detected between flat and irregular levels. Disc height of irregular levels was well preserved in HNP patients. Comparing the two groups, flat levels were more degenerated on MRI in HNP patients. Despite similar degrees of degeneration on MRI, concave and irregular levels in DDD patients had lower disc heights. A higher frequency of symptoms was found in flat and irregular levels for both patient groups. The sagittal profile of end plates in the lumbar spine was described for patients with DDD on the one and HNP on the other. A higher association with symptoms was observed for flat and irregular levels in both patient groups. In DDD patients, disck degeneration on both MRI and

  1. Mesenchymal stem cells injection in degenerated intervertebral disc: cell leakage may induce osteophyte formation.

    PubMed

    Vadalà, Gianluca; Sowa, Gwendolyn; Hubert, Mark; Gilbertson, Lars G; Denaro, Vincenzo; Kang, James D

    2012-05-01

    Recent studies have shown that mesenchymal stem cell (MSC)-based therapy might be an effective approach for the treatment of intervertebral disc degeneration (IDD). However, many unanswered questions remain before clinical translation, such as the most effective stem cell type, a reliable transplantation method, including the carrier choice, and the fate of stem cells after misdirected delivery, among others. The objective of the study was to evaluate the fate and effect of allogenic bone marrow MSCs after transplantation into an IDD model. The L2-3, L3-4 and L4-5 intervertebral discs (IVDs) of four rabbits were stabbed to create IDD. Rabbit MSCs were expanded in vitro and in part transduced with retrovirus/eGFP. After 3 weeks, 1 × 10(5) MSCs were injected into the IVDs. The rabbits were followed by X-ray and MRI 3 and 9 weeks after injection. Then the animals were sacrificed and the spines analysed histologically. MRI showed no signs of regeneration. X-ray and gross anatomy inspection demonstrated large anterolateral osteophytes. Histological analysis showed that the osteophytes were composed of mineralized tissue surrounded by chondrocytes, with the labelled MSCs among the osteophyte-forming cells. The labelled MSCs were not found in the nucleus. Inflammatory cells were not observed in any injected IVDs. These results raise concern that MSCs can migrate out of the nucleus and undesirable bone formation may occur. While cause cannot be inferred from this study, the presence of MSCs in the osteophytes suggests a potential side-effect with this approach. IVD regeneration strategies need to focus on cell carrier systems and annulus-sealing technologies to avoid pitfalls.

  2. The Involvement of Protease Nexin-1 (PN1) in the Pathogenesis of Intervertebral Disc (IVD) Degeneration

    PubMed Central

    Wu, Xinghuo; Liu, Wei; Duan, Zhenfeng; Gao, Yong; Li, Shuai; Wang, Kun; Song, Yu; Shao, Zengwu; Yang, Shuhua; Yang, Cao

    2016-01-01

    Protease nexin-1 (PN-1) is a serine protease inhibitor belonging to the serpin superfamily. This study was undertaken to investigate the regulatory role of PN-1 in the pathogenesis of intervertebral disk (IVD) degeneration. Expression of PN-1 was detected in human IVD tissue of varying grades. Expression of both PN-1 mRNA and protein was significantly decreased in degenerated IVD, and the expression levels of PN-1 were correlated with the grade of disc degeneration. Moreover, a decrease in PN-1 expression in primary NP cells was confirmed. On induction by IL-1β, the expression of PN-1 in NP cells was decreased at day 7, 14, and 21, as shown by western blot analysis and immunofluorescence staining. PN-1 administration decreased IL-1β-induced MMPs and ADAMTS production and the loss of Agg and Col II in NP cell cultures through the ERK1/2/NF-kB signaling pathway. The changes in PN-1 expression are involved in the pathogenesis of IVD degeneration. Our findings indicate that PN-1 administration could antagonize IL-1β-induced MMPs and ADAMTS, potentially preventing degeneration of IVD tissue. This study also revealed new insights into the regulation of PN-1 expression via the ERK1/2/NF-kB signaling pathway and the role of PN-1 in the pathogenesis of IVD degeneration. PMID:27460424

  3. [Stimulation of degenerative changes in the intervertebral disc through axial compression. Radiologic, histologic and biomechanical research in an animal model].

    PubMed

    Unglaub, F; Lorenz, H; Nerlich, A; Richter, W; Kroeber, M W

    2003-01-01

    Degeneration of the intervertebral disc is a common disease in the adults, especially at advanced age. A causal therapy is not known, but the progress in new therapeutic strategies, for example in tissue engineering, shows new possibilities. The goal of our study was to develop a new animal model that stimulates a load induced degeneration of the disc. We used the New Zealand rabbit, because morphology is similar to the human intervertebral disc. The degeneration was induced by axial compression of the disc L4 - L5 with an external fixateur. After different loading intervals, the animals were sacrified and the discs examined by radiology, histology, apoptosis and biomechanical testing. Radiography showed a significant decrease of the disc thickness in all loaded groups. Morphologically the intervertebral discs of loaded rabbits showed degenerative changes which were comparable to those in humans. A significantly increased number of dead cells in the annulus occurred after 14 and 28 days loading compared to the controls. The bending stress measured as the load to failure was not significantly different between the unloaded discs and the 28 days loaded discs. The results show that our animal modell can create degeneration. Four weeks compression leads to significant degeneration. Degeneration of the discs persisted in animals that were allowed a recovery time of 28 days after 28 days of loading.

  4. Injection of human umbilical tissue–derived cells into the nucleus pulposus alters the course of intervertebral disc degeneration in vivo

    PubMed Central

    Leckie, Steven K.; Sowa, Gwendolyn A.; Bechara, Bernard P.; Hartman, Robert A.; Coelho, Joao Paulo; Witt, William T.; Dong, Qing D.; Bowman, Brent W.; Bell, Kevin M.; Vo, Nam V.; Kramer, Brian C.; Kang, James D.

    2016-01-01

    Background context Patients often present to spine clinic with evidence of intervertebral disc degeneration (IDD). If conservative management fails, a safe and effective injection directly into the disc might be preferable to the risks and morbidity of surgery. Purpose To determine whether injecting human umbilical tissue–derived cells (hUTC) into the nucleus pulposus (NP) might improve the course of IDD. Design Prospective, randomized, blinded placebo–controlled in vivo study. Patient sample Skeletally mature New Zealand white rabbits. Outcome measures Degree of IDD based on magnetic resonance imaging (MRI), biomechanics, and histology. Methods Thirty skeletally mature New Zealand white rabbits were used in a previously validated rabbit annulotomy model for IDD. Discs L2–L3, L3–L4, and L4–L5 were surgically exposed and punctured to induce degeneration and then 3 weeks later the same discs were injected with hUTC with or without a hydrogel carrier. Serial MRIs obtained at 0, 3, 6, and 12 weeks were analyzed for evidence of degeneration qualitatively and quantitatively via NP area and MRI Index. The rabbits were sacrificed at 12 weeks and discs L4–L5 were analyzed histologically. The L3–L4 discs were fixed to a robotic arm and subjected to uniaxial compression, and viscoelastic displacement curves were generated. Results Qualitatively, the MRIs demonstrated no evidence of degeneration in the control group over the course of 12 weeks. The punctured group yielded MRIs with the evidence of disc height loss and darkening, suggestive of degeneration. The three treatment groups (cells alone, carrier alone, or cells+carrier) generated MRIs with less qualitative evidence of degeneration than the punctured group. MRI Index and area for the cell and the cell+carrier groups were significantly distinct from the punctured group at 12 weeks. The carrier group generated MRI data that fell between control and punctured values but failed to reach a statistically

  5. Characterization of in vivo effects of platelet-rich plasma and biodegradable gelatin hydrogel microspheres on degenerated intervertebral discs.

    PubMed

    Sawamura, Kazuhide; Ikeda, Takumi; Nagae, Masateru; Okamoto, Shin-ichi; Mikami, Yasuo; Hase, Hitoshi; Ikoma, Kazuya; Yamada, Tetsuya; Sakamoto, Hirotaka; Matsuda, Ken-ichi; Tabata, Yasuhiko; Kawata, Mitsuhiro; Kubo, Toshikazu

    2009-12-01

    We have previously shown that administration of platelet-rich plasma-impregnated gelatin hydrogel microspheres (PRP-GHMs) into a degenerated intervertebral disc (IVD) markedly suppresses progression of IVD degeneration. In the current study, we characterized the in vivo effects of PRP-GHM treatment in a degenerated IVD model in rabbit. On magnetic resonance images, the IVD height was significantly greater after treatment with PRP-GHMs compared with phosphate-buffered saline-impregnated GHMs, PRP without GHMs, and needle puncture only. Water content was also preserved in PRP-GHM-treated IVDs. Consistent with this observation, the mRNA expression of proteoglycan core protein and type II collagen was significantly higher after PRP-GHM treatment compared with other treatment groups. No proliferating cells were found in the nucleus pulposus and inner annulus fibrosus in any groups, but the number of apoptotic cells in the nucleus pulposus after PRP-GHM treatment was significantly lower than that after other treatments. These results provide an improved understanding of the therapeutic effects of PRP-GHM treatment of degenerated IVDs.

  6. Association Between Lumbar Disc Degeneration and Propionibacterium acnes Infection: Clinical Research and Preliminary Exploration of Animal Experiment.

    PubMed

    Li, Bo; Dong, Zhe; Wu, Yongchao; Zeng, Ji; Zheng, Qixin; Xiao, Baojun; Cai, Xianyi; Xiao, Zhiyong

    2016-07-01

    Clinical research and animal experiment. To investigate whether lumbar disc degeneration is associated with Propionibacterium acnes (P acnes) infection. The hypothesis that herniated discs may be infected with P acnes by way of bacteremia is remarkable. This may bring a tremendous change in treatment of lumbar disc herniation (LDH). However, this hypothesis is still controversial. Since P acnes isolated may be related to contamination. Nucleus pulposus from 22 patients (30 discs) with lumbar disc herniation was collected during discectomy, following aerobic and anaerobic cultures for 10 days.Twenty-four rabbits were divided into four groups. After L3-L6 being exposed, an incision was made into the three discs in groups A and B. While in groups C and D, two random segments were operated. Six weeks later, 0.05 mL of 5 × 10 CFU/mL P acnes was inoculated into operated discs in group A and sterile physiological saline in group B. In group C, 0.2 mL of 5 × 10 CFU/mL P acnes was injected through ear vein. Sterile saline was used in group D. Six weeks later, MRI was performed. Then, nucleus pulposus and paraspinal muscles were harvested for aerobic and anaerobic cultures. Clinical research: Anaerobic cultures were positive in three cases: two coagulase-negative staphylococci, one particles chain bacterium. No P acnes was found. Staphylococcus epidermidis was isolated in one aerobic culture.Animal experiment: P acnes was found in 11 out of 18 (61%) discs in group A. There was no P acnes found in the other three groups. Degenerated discs were suitable for P acnes growth. This research did not find the evidence of the symptomatic degenerated lumbar discs infected with P acnes or that P acnes could infect the degenerated lumbar discs by way of bacteremia. N/A.

  7. Viscoelastic Disc Arthroplasty Provides Superior Back and Leg Pain Relief in Patients with Lumbar Disc Degeneration Compared to Anterior Lumbar Interbody Fusion.

    PubMed

    Rischke, Burkhard; Zimmers, Kari B; Smith, Eric

    2015-01-01

    Lumbar disc degeneration (LDD) is one of the most frequently diagnosed spinal diseases. The symptoms these disorders cause are anticipated to increase as the population in Western countries ages. Compare back and leg pain alleviation in patients with LDD and a viscoelastic disc prosthesis documented in the SWISSspine registry versus patients with anterior lumbar interbody fusion documented in the Spine Tango registry. Prospectively collected clinical and outcome data in two independent spine registries. Outcome Measures were back and leg pain relief on 0 to 10 numerical rating scales. The analysis included a single surgeon series of 48 patients with viscoelastic total disc replacement (VTDR) from the SWISSspine registry which were compared to 131 patients with anterior lumbar interbody fusion (ALIF) from the Spine Tango registry. Two linear multivariate regression models were built to assess the associations of patient characteristics with back and leg pain relief. The following covariates were included in the models: patient age and sex, disc herniation as additional diagnosis, number of treated segments, level of treated segment, treatment type (VTDR, ALIF), preoperative back and leg pain levels and follow-up interval. Both models showed VTDR to be associated with significantly higher back (2.76 points; 95% confidence interval (CI) 1.78 - 3.73; p < 0.001) and leg pain (2.12 points; 95% CI 1.12 to 3.13; p < 0.001) relief than ALIF. Other influential factors for higher back pain relief were female sex compared with male sex (1.03 additional points; 95% CI 0.27 to 1.78; p = 0.008), monosegmental surgery compared with bisegmental surgery (1.02 additional points; 95% CI 0.21 to 1.83; p = 0.014), and higher back pain at baseline (0.87 points additional pain relief per level of preoperative back pain; 95% CI 0.70 to 1.03; p < 0.001). Other influential factors for leg pain relief were monosegmental surgery (0.93 additional points; 95% CI 0.10 to 1.77; p = 0.029) and

  8. Association between menopause and lumbar disc degeneration: an MRI study of 1,566 women and 1,382 men.

    PubMed

    Lou, Chao; Chen, Hongliang; Mei, Liangwei; Yu, Weiyang; Zhu, Kejun; Liu, Feijun; Chen, Zhenzhong; Xiang, Guangheng; Chen, Minjiang; Weng, Qiaoyou; He, Dengwei

    2017-10-01

    The aim of this study was to revisit and further investigate the association between menopause and disc degeneration in the lumbar spine using a magnetic resonance imaging-based eight-level grading system. This study cohort comprised of 1,566 women and 1,382 age-matched men who were admitted for low back pain from June 2013 to October 2016. Data on age, weight, height, body mass index, age at natural menopause, and years since menopause (YSM) were obtained. Lumbar disc degeneration was assessed using a magnetic resonance imaging-based eight-level grading system. After adjustment for the confounding factors of age, height, and weight, young age-matched men were more susceptible to disc degeneration than premenopausal women (P < 0.05). However, after menopause, postmenopausal women had a significant tendency to develop more severe disc degeneration than their age-matched men (P < 0.05), and also compared with premenopausal and perimenopausal women (P < 0.01). Postmenopausal women were divided into nine subgroups by every 5 YSM. When YSM was less than 15 years, a positive trend was observed between YSM and severity of disc degeneration, respectively, at L1/L2 (r = 0.241), L2/L3 (r = 0.193), L3/L4 (r = 0.191), L4/L5 (r = 0.165), L5/S1 (r = 0.153), and all lumbar discs (r = 0.237) (P < 0.05 or 0.01). The analysis of covariance indicated a significant difference in each disc level (P < 0.05 or 0.01) between every two groups. When YSM was more than 15 years, the significant difference, however, disappeared in each disc level (P > 0.05). Menopause is associated with lumbar disc degeneration. The association occurred in the first 15 YSM, suggesting estrogen deficiency might be a risk factor of disc degeneration of the lumbar spine. Further studies need to be carried out for deciding whether age or menopause plays a more important role in the progression of disc degeneration in the lumbar spine.

  9. Progression and determinants of quantitative magnetic resonance imaging measures of lumbar disc degeneration: a five-year follow-up of adult male monozygotic twins.

    PubMed

    Videman, Tapio; Battié, Michele C; Parent, Eric; Gibbons, Laura E; Vainio, Pauli; Kaprio, Jaakko

    2008-06-01

    A longitudinal study. Our goal was to explore the role of digital magnetic resonance imaging (MRI) data, by extending our earlier 5-year follow-up study of progression of lumbar spine degeneration with quantitative measures of disc degeneration. A longitudinal study is optimal for investigating disc degeneration but only a few studies (with small sample sizes) or short follow-up studies include repeated MRI data. Subjects consisted of 134 male monozygotic twins (age 35-69 years). Quantitative MRI measures included changes in disc bulging and height. Inter-rater reliability coefficients were between 0.77 and 0.96. At baseline and follow-up, an extensive interview about exposures to suspected determinants was conducted. Reduction in disc height and increases in bulges (worsening) were seen in 2/3 of subjects. The mean reduction in disc height was 2.2% to 3.6%. A mean increase in bulging of 7% to 10% was found in the L1-L4 discs and 4% in L4-S1 discs. Although the mean changes were small, few reverse changes were observed. Familial aggregation, a proxy for genetic influences, explained 17% of changes in disc height, and 11% and 0% of changes in the sizes of anterior and posterior bulges in the regression models. Higher maximal occupational lifting (AR2 = 4.9%) and smoking (AR2 = 3.5%) during follow-up predicted more disc height reduction. Greater increases in bulging (AR2 = 7.4%-10.2%) were predicted by smaller bulges at baseline. The mean annual changes in disc heights (<1%) and bulges (<2%) were small, and included both decreases and increases, with only a few subjects showing more major changes in either direction. The role of genetics was largest except in posterior bulges, but lifting and smoking were also associated with disc height reduction but none of the other studied risk factors were associated with anterior or posterior disc bulging. Different degenerative findings have different determinants of progression.

  10. ADAMTS-4 and ADAMTS-5 expression in human temporomandibular joint discs with internal derangement, correlates with degeneration.

    PubMed

    Leonardi, Rosalia; Crimi, Salvatore; Almeida, Luis Eduardo; Pannone, Giuseppe; Musumeci, Giuseppe; Castorina, Sergio; Rusu, Mugurel Constantin; Loreto, Carla

    2015-11-01

    Temporomandibular joint (TMJ) internal derangement (ID) is one of the most common form of temporomandibular disorders. There is evidence showing the increased expression of matrix metalloproteinases (MMPs) in the cells from degenerated TMJ disc. ADAMTS are a large family of metalloproteases which are responsible for proteoglycans degradation. The present study aimed to evaluate ADAMTS-4 and ADAMTS-5 immunohistochemical expression in human TMJ discs from patients affected by ID, and to find out if there is any correlation with the degree of histopathological changes. Eighteen temporomandibular displaced disc specimens and sixteen TMJ disc control were used for the present study. Specimens were immunohistochemically processed and ADAMTS-4 and ADAMTS-5 expression were obtained respectively for the anterior (AB), intermediate (IB) and posterior (PB) bands and compared to the histopathological degeneration score (HDS). Immunoreactivity for ADAMTS-4 and -5, was observed in both not degenerated and degenerated human TMJ discs. Both the percentage of ADAMTS-4 and -5 immunostained cells (ES) and the intensity of staining (IS) were significantly greater in affected specimens compared with those in control discs. The ADAMTS-5 ES and IS of the 3 bands of the disc correlated to the TMJ disc HDS (0.001 < P < 0.05), on the other hand only AB and IB, ADAMTS-4 immunostaining scores correlated to HDS. According to these findings it can be assumed in that the more histopathological changes in the disc are detected, the higher levels of ADAMTS are produced. This in turn can lead to ECM breakdown and in turn to a more advanced disc displacement. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Pulsed electromagnetic field (PEMF) treatment reduces expression of genes associated with disc degeneration in human intervertebral disc cells.

    PubMed

    Miller, Stephanie L; Coughlin, Dezba G; Waldorff, Erik I; Ryaby, James T; Lotz, Jeffrey C

    2016-06-01

    Pulsed electromagnetic field (PEMF) therapies have been applied to stimulate bone healing and to reduce the symptoms of arthritis, but the effects of PEMF on intervertebral disc (IVD) biology is unknown. The purpose of this study was to determine how PEMF affects gene expression of IVD cells in normal and inflammatory environments. This was an in vitro human cell culture and microarray gene expression study. Human annulus fibrosus (AF) and nucleus pulposus (NP) cells were separately encapsulated in alginate beads and exposed to interleukin 1α (IL-1α) (10 ng/mL) to stimulate the inflammatory environment associated with IVD degeneration and/or stimulated by PEMF for 4 hours daily for up to 7 days. RNA was isolated from each treatment group and analyzed via microarray to assess IL-1α- and PEMF-induced changes in gene expression. Although PEMF treatment did not completely inhibit the effects of IL-1α, PEMF treatment lessened the IL-1α-induced upregulation of genes expressed in degenerated IVDs. Consistent with our previous results, after 4 days, PEMF tended to reduce IL-1α-associated gene expression of IL-6 (25%, p=.07) in NP cells and MMP13 (26%, p=.10) in AF cells. Additionally, PEMF treatment significantly diminished IL-1α-induced gene expression of IL-17A (33%, p=.01) and MMP2 (24%, p=.006) in NP cells and NFκB (11%, p=.04) in AF cells. These results demonstrate that IVD cells are responsive to PEMF and motivate future studies to determine whether PEMF may be helpful for patients with IVD degeneration. Copyright © 2016. Published by Elsevier Inc.

  12. Cell and molecular biology of intervertebral disc degeneration: current understanding and implications for potential therapeutic strategies.

    PubMed

    Wang, S Z; Rui, Y F; Lu, J; Wang, C

    2014-10-01

    Intervertebral disc degeneration (IDD) is a chronic, complex process associated with low back pain; mechanisms of its occurrence have not yet been fully elucidated. Its process is not only accompanied by morphological changes, but also by systematic changes in its histological and biochemical properties. Many cellular and molecular mechanisms have been reported to be related with IDD and to reverse degenerative trends, abnormal conditions of the living cells and altered cell phenotypes would need to be restored. Promising biological therapeutic strategies still rely on injection of active substances, gene therapy and cell transplantation. With advanced study of tissue engineering protocols based on cell therapy, combined use of seeding cells, bio-active substances and bio-compatible materials, are promising for IDD regeneration. Recently reported progenitor cells within discs themselves also hold prospects for future IDD studies. This article describes the background of IDD, current understanding and implications of potential therapeutic strategies.

  13. High Prevalence of Disc Degeneration and Spondylolysis in the Lumbar Spine of Professional Beach Volleyball Players

    PubMed Central

    Külling, Fabrice A.; Florianz, Hannes; Reepschläger, Bastian; Gasser, Johann; Jost, Bernhard; Lajtai, Georg

    2014-01-01

    Background: Beach volleyball is an intensive sport with high impact on the lumbar spine. Low back pain (LBP) is frequent among elite players. Increased prevalence of pathological changes on magnetic resonance imaging (MRI) in the lumbar spine of elite athletes has been reported. Hypothesis: There is an increased prevalence of disc degeneration and spondylolysis in the MRI of the lumbar spine of professional beach volleyball players. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Twenty-nine fully competitive professional male volleyball players (mean age, 28 years) completed outcomes questionnaires and underwent a complete clinical examination and an MRI of their lumbar spine. Results: Whereas 86% of players suffered from LBP during their career, the incidence of LBP in the last 4 weeks was 35%. Pain rated using a visual analog scale (VAS) averaged 3 points (range, 0-8). Twenty-three of 29 players (79%) had at least 1 degenerated disc of Pfirrmann grade ≥3. The most affected spinal levels were L4-5 in 14 (48%) and L5-S1 in 15 players (52%); both levels were involved in 5 players (17%). Six of 29 (21%) players showed a spondylolysis grade 4 according to the Hollenburg classification; there was evidence of spondylolisthesis in 2 players. There was no significant correlation between LBP and MRI abnormalities. Conclusion: In the lumbar spine MRI of professional beach volleyball players, the prevalence of disc degeneration is 79%. Spondylolysis (21%) is up to 3 times higher compared with the normal population. Abnormal MRI findings did not correlate with LBP, thus MRIs have to be interpreted with caution. PMID:26535316

  14. Thermochemical modelling of brown dwarf discs

    NASA Astrophysics Data System (ADS)

    Greenwood, A. J.; Kamp, I.; Waters, L. B. F. M.; Woitke, P.; Thi, W.-F.; Rab, Ch.; Aresu, G.; Spaans, M.

    2017-05-01

    The physical properties of brown dwarf discs, in terms of their shapes and sizes, are still largely unexplored by observations. ALMA has by far the best capabilities to observe these discs in sub-mm CO lines and dust continuum, while also spatially resolving some discs. To what extent brown dwarf discs are similar to scaled-down T Tauri discs is currently unknown, and this work is a step towards establishing a relationship through the eventual modelling of future observations. We use observations of the brown dwarf disc ρ Oph 102 to infer a fiducial model around which we build a small grid of brown dwarf disc models, in order to model the CO, HCN, and HCO+ line fluxes and the chemistry which drives their abundances. These are the first brown dwarf models to be published which relate detailed, 2D radiation thermochemical disc models to observational data. We predict that moderately extended ALMA antenna configurations will spatially resolve CO line emission around brown dwarf discs, and that HCN and HCO+ will be detectable in integrated flux, following our conclusion that the flux ratios of these molecules to CO emission are comparable to that of T Tauri discs. These molecules have not yet been observed in sub-mm wavelengths in a brown dwarf disc, yet they are crucial tracers of the warm surface-layer gas and of ionization in the outer parts of the disc. We present the prediction that if the physical and chemical processes in brown dwarf discs are similar to those that occur in T Tauri discs - as our models suggest - then the same diagnostics that are used for T Tauri discs can be used for brown dwarf discs (such as HCN and HCO+ lines that have not yet been observed in the sub-mm), and that these lines should be observable with ALMA. Through future observations, either confirmation (or refutation) of these ideas about brown dwarf disc chemistry will have strong implications for our understanding of disc chemistry, structure, and subsequent planet formation in brown

  15. Comparative gene expression profiling of normal and degenerative discs: analysis of a rabbit annular laceration model.

    PubMed

    Anderson, D Greg; Izzo, Marc W; Hall, David J; Vaccaro, Alexander R; Hilibrand, Alan; Arnold, William; Tuan, Rocky S; Albert, Todd J

    2002-06-15

    A rabbit annular laceration model was used to investigate intervertebral disc gene expression in normal and lacerated discs. To determine and compare the pattern of expression of potentially important genes in normal and lacerated discs and to determine if the changes in gene expression were similar to human degenerative discs. Little is known regarding gene expression in normal or degenerating disc tissue. Eighteen rabbits were subjected to annular laceration of the L1-L2 and L2-L3 discs while two rabbits served as sham controls. Control and lacerated discs were harvested 1 week, 3 weeks, and 6 weeks following surgery and subjected to histologic examination and gene expression analysis using the reverse transcription-polymerase chain reaction (RT-PCR). The genes studied included collagen Type I (Col I), collagen Type II (Col II), decorin, fibronectin (FN), interleukin-1a (IL-1alpha), bone morphogenetic protein 2 (BMP-2), Fas, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 9 (MMP-9), matrix metalloproteinase 13 (MMP-13), and tumor necrosis factor (TNF). Expression levels of each gene were normalized to that of glyceraldehyde-3-phosphate dehydrogenase (GADPH), a constitutively expressed gene. Histology confirmed progressive degeneration of the discs over the 6-week study period. Different patterns of gene expression were observed in control and lesioned discs. Annular laceration caused a marked upregulation (two- to eightfold) of the expression of Col I, Col II, FN, MMP-1, MMP-9, MMP-13, and Fas genes, whereas that of BMP-2, IL-1alpha, and TNF genes was unaffected. Expression of the decorin gene was downregulated approximately sixfold after annular laceration. Annular laceration in this animal model resulted in marked changes in gene expression. Upregulation of gene expression was observed for some molecules found at high concentration in human degenerated discs, suggesting similarities to human disc degeneration at the molecular level. This supports

  16. Autophagy in the Degenerating Human Intervertebral Disc: In Vivo Molecular and Morphological Evidence, and Induction of Autophagy in Cultured Annulus Cells Exposed to Proinflammatory Cytokines-Implications for Disc Degeneration.

    PubMed

    Gruber, Helen E; Hoelscher, Gretchen L; Ingram, Jane A; Bethea, Synthia; Hanley, Edward N

    2015-06-01

    Autophagy-related gene expression and ultrastructural features of autophagy were studied in human discs. To obtain molecular/morphological data on autophagy in human disc degeneration and cultured human annulus cells exposed to proinflammatory cytokines. Autophagy is an important process by which cytoplasm and organelles are degraded; this adaptive response to sublethal stresses (such as nutrient deprivation present in disc degeneration) supplies needed metabolites. Little is known about autophagic processes during disc degeneration. Human disc specimens were obtained after institutional review board approval. Annulus mRNA was analyzed to determine autophagy-related gene expression levels. Immunolocalization and ultrastructural studies for p62, ATG3, ATG4B, ATG4C, ATG7, L3A, ULK-2, and beclin were conducted. In vitro experiments used IL-1β- or TNF-α-treated human annulus cells to test for autophagy-related gene expression. More degenerated versus healthier discs showed significantly greater upregulation of well-recognized autophagy-related genes (P ≤ 0.028): beclin 1 (upregulated 1.6-fold); ATG8 (LC3) (upregulated 2.0-fold); ATG12 (upregulated 4.0-fold); presenilin 1 (upregulated 1.6-fold); cathepsin B (upregulated 4.5-fold). p62 was localized, and ultrastructure showed autophagic vacuolization and autophagosomes with complex, redundant whorls of membrane-derived material. In vitro, proinflammatory cytokines significantly upregulated autophagy-related genes (P ≤ 0.04): DRAM1 (6.24-fold); p62 (4.98-fold); PIM-2 oncogene, a positive regulator of autophagy (3-fold); WIPI49 (linked to starvation-induced autophagy) (upregulated 2.3-fold). Data provide initial molecular and morphological evidence for the presence of autophagy in the degenerating human annulus. In vivo gene analyses showed greater autophagy-related gene expression in more degenerated than healthier discs. In vitro data suggested a mechanism implicating a role of TNF-α and IL-1β in disc autophagy

  17. 2D segmentation of intervertebral discs and its degree of degeneration from T2-weighted magnetic resonance images

    NASA Astrophysics Data System (ADS)

    Castro-Mateos, Isaac; Pozo, José Maria; Lazary, Aron; Frangi, Alejandro F.

    2014-03-01

    Low back pain (LBP) is a disorder suffered by a large population around the world. A key factor causing this illness is Intervertebral Disc (IVD) degeneration, whose early diagnosis could help in preventing this widespread condition. Clinicians base their diagnosis on visual inspection of 2D slices of Magnetic Resonance (MR) images, which is subject to large interobserver variability. In this work, an automatic classification method is presented, which provides the Pfirrmann degree of degeneration from a mid-sagittal MR slice. The proposed method utilizes Active Contour Models, with a new geometrical energy, to achieve an initial segmentation, which is further improved using fuzzy C-means. Then, IVDs are classified according to their degree of degeneration. This classification is attained by employing Adaboost on five specific features: the mean and the variance of the probability map of the nucleus using two different approaches and the eccentricity of the fitting ellipse to the contour of the IVD. The classification method was evaluated using a cohort of 150 intervertebral discs assessed by three experts, resulting in a mean specificity (93%) and sensitivity (83%) similar to the one provided by every expert with respect to the most voted value. The segmentation accuracy was evaluated using the Dice Similarity Index (DSI) and Root Mean Square Error (RMSE) of the point-to-contour distance. The mean DSI ± 2 standard deviation was 91:7% ±5:6%, the mean RMSE was 0:82mm and the 95 percentile was 1:36mm. These results were found accurate when compared to the state-of-the-art.

  18. Association between TRAIL gene polymorphisms and the susceptibility and severity of lumbar disc degeneration

    PubMed Central

    Du, Heng; Bai, Bin; Qiu, Yusheng; Yin, Si; Bian, Weiguo

    2015-01-01

    Aim: The aim of the present study was to investigate the association between tumor necrosis factor related apoptosis-inducing ligand (TRAIL) gene polymorphisms and the susceptibility and severity of lumbar disc degeneration (LDD) in the Chinese Han population. Methods: A total of 153 patients with LDD and 131 healthy subjects were enrolled in the study. Four single-nucleotide polymorphisms (SNPs) in the 3’ untranslated region (3’UTR) of TRAIL gene, including 1289 C/A, 1525 G/A, 1588 G/A and 1595 C/T, were genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: The genotypes and alleles frequencies of TRAIL at 1525 and 1595 positions in all subjects were the same. There was a significant association between TRAIL 1525/1595 polymorphisms and the susceptibility of LDD. The frequencies of 1525 GG /1595 CC genotype, and 1525 G/1595 C allele were higher in the patients group than that in the control group. In addition, we found patients with the 1525 AA /1595 TT genotype, as well as 1525 A/1595 T allele exhibit significantly low frequency of high grades of disc degeneration. However, there were no significant differences in the genotype or allele distribution of TRAIL 1289 C/A or 1588 G/A between the patients and the control group. Conclusion: TRAIL 1525/1595 polymorphisms were associated with the susceptibility and severity of LDD in the Chinese Han population. PMID:26261645

  19. Nerves are more abundant than blood vessels in the degenerate human intervertebral disc.

    PubMed

    Binch, Abbie L A; Cole, Ashley A; Breakwell, Lee M; Michael, Antony L R; Chiverton, Neil; Creemers, Laura B; Cross, Alison K; Le Maitre, Christine L

    2015-12-21

    Chronic low back pain (LBP) is the most common cause of disability worldwide. New ideas surrounding LBP are emerging that are based on interactions between mechanical, biological and chemical influences on the human IVD. The degenerate IVD is proposed to be innervated by sensory nerve fibres and vascularised by blood vessels, and it is speculated to contribute to pain sensation. However, the incidence of nerve and blood vessel ingrowth, as well as whether these features are always associated, is unknown. We investigated the presence of nerves and blood vessels in the nucleus pulposus (NP) of the IVD in a large population of human discs. Immunohistochemistry was performed with 61 human IVD samples, to identify and localise nerves (neurofilament 200 [NF200]/protein gene product 9.5) and blood vessels (CD31) within different regions of the IVD. Immunopositivity for NF200 was identified within all regions of the IVD within post-mortem tissues. Nerves were seen to protrude across lamellar ridges and through matrix towards NP cells. Nerves were identified deep within the NP and were in many cases, but not always, seen in close proximity to fissures or in areas where decreased matrix was seen. Fifteen percent of samples were degenerate and negative for nerves and blood vessels, whilst 16 % of all samples were degenerate with nerves and blood vessels. We identified 52% of samples that were degenerate with nerves but no blood vessels. Interestingly, only 4% of all samples were degenerate with no nerves but positive for blood vessels. Of the 85 samples investigated, only 6 % of samples were non-degenerate without nerves and blood vessels and 7% had nerves but no blood vessels. This study addresses the controversial topic of nerve and blood vessel ingrowth into the IVD in a large number of human samples. Our findings demonstrate that nerves are present within a large proportion of NP samples from degenerate IVDs. This study shows a possible link between nerve ingrowth and

  20. [Correlation between shape and direction of small articular surface in lower lumbar vertebrae and degeneration of intervertebral disc].

    PubMed

    Tan, L; Bai, X; Li, D

    1997-01-01

    To assess the possible correlation between the shape and the direction of the small articular surface in the lower lumbar vertebrae and the degeneration of the intervertebral disc, we investigated with computed tomography (CT) and evaluated with statistics the small articular surface and the transverse interface-joint angle (TIFA) of the L4-5 and the L5-S1 in 152 cases who had normal or degenerative discs verified through CT, MRI or operation. The small articular surface was found arc in 69.1% of the L4-5 and in 23.0% of the L5-S1. The TIFA of the L4-5 was less than that of the L5-S1. There was no correlation between the ratio of degeneration of the intervertebral disc at the L4-5 and the TIFA of the L4-5 and the L5-S1, but the ratio of degeneration of the intervertebral disc at the L5-S1 had postive correlation with the TIFA of the L4-5, negative correlation with the TIFA of the L5-S1, and particular correlation with the TIFA of the L5-S1 and L4-5. These results suggest that the shape and direction of the lower lumbar facet joint are related to the lumbar degeneration of intervertebral disc and the causes of degeneration at the L4-5 disc differ from those at the L5-S1 disc in biomechanics.

  1. Analysis of quantitative magnetic resonance imaging and biomechanical parameters on human discs with different grades of degeneration.

    PubMed

    Antoniou, John; Epure, Laura M; Michalek, Arthur J; Grant, Michael P; Iatridis, James C; Mwale, Fackson

    2013-12-01

    To establish relationships between quantitative MRI (qMRI) and biomechanical parameters in order to help inform and interpret alterations of human intervertebral discs (IVD) with different grades of degeneration. The properties of the nucleus pulposus (NP) and annulus fibrosus (AF) of each IVD of 10 lumbar spines (range, 32-77 years) were analyzed by qMRI (relaxation times T1 and T2, magnetization transfer ratio [MTR], and apparent diffusion coefficient [ADC]), and tested in confined compression and dynamic shear. T1 and T2 significantly decreased in both the NP and AF with increasing degeneration grades while the MTR increased significantly with grade 4. In contrast to the other qMRI parameters, the ADC had a tendency to decrease with increasing grade. Disc degeneration caused a decrease in the aggregate modulus, hydraulic permeability and shear modulus magnitude along with an increase in phase angle in the AF. In contrast, disc degeneration of NPs demonstrated decreases in shear modulus and phase angle. Our studies indicate that qMRI can be used as a noninvasive diagnostic tool in the detection of IVD properties with the potential to help interpret and detect early, middle, and late stages of degeneration. QMRI of human IVD can therefore become a very important diagnostic assessment tool in determining the functional state of the disc. Copyright © 2013 Wiley Periodicals, Inc.

  2. Analysis of Quantitative Magnetic Resonance Imaging and Biomechanical Parameters on Human Discs with Different Grades of Degeneration

    PubMed Central

    Antoniou, John; Epure, Laura M.; Michalek, Arthur J.; Grant, Michael P.; Iatridis, James C.; Mwale, Fackson

    2013-01-01

    Purpose To establish relationships between quantitative magnetic resonance imaging (qMRI) and biomechanical parameters to help inform and interpret alterations of human intervertebral discs (IVD) with different grades of degeneration. Materials and Methods The properties of the nucleus pulposus (NP) and annulus fibrosus (AF) tissues of each IVD of 10 lumbar spines (range 32–77 years) were analyzed by qMRI (relaxation times T1 and T2, magnetization transfer ratio MTR and apparent diffusion coefficient ADC), and tested in confined compression and dynamic shear. Results T1 and T2 significantly decreased in both the NP and AF with increasing degeneration grades while the MTR increased significantly with grade 4. In contrast with the others qMRI parameters, the ADC had a tendency to decrease with increasing grade. Disc degeneration caused a decrease in the aggregate modulus, hydraulic permeability and shear modulus magnitude along with an increase in phase angle in the AF. On the other hand, disc degeneration of NPs decreased the shear modulus and the phase angle. Conclusion Our studies indicate that qMRI can be used as a non-invasive diagnostic tool in the detection of IVDs properties with potential to help interpret and to detect early, middle and late stages of degeneration. QMRI of the human IVD can therefore become a very important diagnostic assessment tool in determining the functional state of the disc. PMID:23633131

  3. Lumbar disc degeneration was not related to spine and hip bone mineral densities in Chinese: facet joint osteoarthritis may confound the association.

    PubMed

    Pan, Jianjiang; Lu, Xuan; Yang, Ge; Han, Yongmei; Tong, Xiang; Wang, Yue

    2017-12-01

    A sample of 512 Chinese was studied and we observed that greater disc degeneration on MRI was associated with greater spine DXA BMD. Yet, this association may be confounded by facet joint osteoarthritis. BMD may not be a risk factor for lumbar disc degeneration in Chinese.

  4. Segmental kinematics and adjacent level degeneration following disc replacement versus fusion: RCT with three years of follow-up.

    PubMed

    Nabhan, A; Steudel, W I; Nabhan, Ah; Pape, D; Ishak, B

    2007-01-01

    Prospective, randomized and controlled clinical and radiological study. The aim of this study was to assess the segmental kinematics and clinical outcome of disc replacement with ProDisc C versus anterior cervical discectomy and fusion (ACDF) for monosegmental disease 3 years after surgery. Anterior cervical discectomy and fusion (ACDF), including plate fixation, is an accepted technique for treatment of symptomatic degenerative disc disease (DDD). However, various studies could show that fusion of a relative mobile spinal segment leads to heightens of stresses on the discs below and above fusion, which is manifested as adjacent level degeneration. Intervertebral disc replacement has been attempted to restore intervertebral disc height and to maintain segmental motion, which may be thought to avoid the accelerated degeneration to the adjacent level. In earlier studies, we could show that ProDisc C could maintain segmental motion for 1 year after surgery. 49 patients with cervical disc herniation underwent arthroplasty of a single level using ProDisc C disc prosthesis or received fusion using a cage and anterior titanium plate fixation. Clinical outcome was assessed using the visual analogue scale (VAS) and the neck disability index (NDI). Radiostereometry was performed immediately postoperative and then after 1, 2, and 3 years after surgery to quantify the segmental kinematics. The range of motion of the treated segment with prosthesis remained unchanged 3 years after surgery in comparison to the 1-year result. The prosthesis shows a significant segmental motion in contrast to the fusion group at each RSA examination time (p < 0.05). After both procedures, a significant pain reduction in neck and arm was observed, without significant differences between both groups. During the course of the 3 years follow-up, no patients of the prosthesis group required further surgical intervention.

  5. Correlation between T2* (T2 star) relaxation time and cervical intervertebral disc degeneration: An observational study.

    PubMed

    Huang, Minghua; Guo, Yong; Ye, Qiong; Chen, Lei; Zhou, Kai; Wang, Qingjun; Shao, Lixin; Shi, Qinglei; Chen, Chun

    2016-11-01

    To demonstrate the potential benefits of T2 relaxation time of intervertebral discs (IVDs) regarding the detection and grading of degenerative disc disease using 3.0-T magnetic resonance imaging (MRI) in a clinical setting. Cervical sagittal T2-weighted, T2 relaxation MRI was performed at 3.0-T in 61 subjects, covering discs C2-3 to C6-7. All discs were morphologically assessed based on the Pfirrmann grade, and regions of interests (ROIs) were drawn over the T2 mapping. Receiver operating characteristic (ROC) analysis was performed among grades to determine the cut-off values. Cervical intervertebral discs (IVDs) of patients were commonly determined to be at Pfirrmann grades III to V. The nucleus pulposus (NP) values did not differ significantly between sexes at the same anatomic level (P > 0.05). In the NP, the T2 values tended to decrease with increasing grade (P < 0.000), and a significant difference was found in the T2 values between grades I to V (P < 0.05). T2 values based on disc degeneration level classification were as follows: grade I (>30 milliseconds), grade II (24.55-29.99 milliseconds), grade III (21.65-24.54 milliseconds), grade IV (18.35-21.64 milliseconds), and grade V (<18.34 milliseconds). Our standardized method of region-specific quantitative T2 relaxation time evaluation seems capable of characterizing different degrees of disc degeneration quantitatively. The T2 values obtained in these cervical IVDs may serve as baseline values for future T2 measurements in both healthy and degenerated cervical discs.

  6. lncRNAs: novel players in intervertebral disc degeneration and osteoarthritis.

    PubMed

    Chen, Wen-Kang; Yu, Xiao-Hua; Yang, Wei; Wang, Cheng; He, Wen-Si; Yan, Yi-Guo; Zhang, Jian; Wang, Wen-Jun

    2017-02-01

    The term long non-coding RNA (lncRNA) refers to a group of RNAs with length more than 200 nucleotides, limited protein-coding potential, and having widespread biological functions, including regulation of transcriptional patterns and protein activity, formation of endogenous small interfering RNAs (siRNAs) and natural microRNA (miRNA) sponges. Intervertebral disc degeneration (IDD) and osteoarthritis (OA) are the most common chronic, prevalent and age-related degenerative musculoskeletal disorders. Numbers of lncRNAs are differentially expressed in human degenerative nucleus pulposus tissue and OA cartilage. Moreover, some lncRNAs have been shown to be involved in multiple pathological processes during OA, including extracellular matrix (ECM) degradation, inflammatory responses, apoptosis and angiogenesis. In this review, we summarize current knowledge concerning lncRNAs, from their biogenesis, classification and biological functions to molecular mechanisms and therapeutic potential in IDD and OA.

  7. Oestrogen and parathyroid hormone alleviate lumbar intervertebral disc degeneration in ovariectomized rats and enhance Wnt/β-catenin pathway activity

    PubMed Central

    Jia, Haobo; Ma, Jianxiong; Lv, Jianwei; Ma, Xinlong; Xu, Weiguo; Yang, Yang; Tian, Aixian; Wang, Ying; Sun, Lei; Xu, Liyan; Fu, Lin; Zhao, Jie

    2016-01-01

    To investigate the mitigation effect and mechanism of oestrogen and PTH on disc degeneration in rats after ovariectomy, as well as on Wnt/β-catenin pathway activity, thirty 3-month-old rats were ovariectomized and divided into three groups. Ten additional rats were used as controls. Eight weeks later, the rats were administered oestrogen or PTH for 12 weeks, and then discs were collected for tests. Results showed that nucleus pulposus cells in the Sham group were mostly notochord cells, while in the OVX group, cells gradually developed into chondrocyte-like cells. Oestrogen or PTH could partly recover the notochord cell number. After ovariectomy, the endplate roughened and endplate porosity decreased. After oestrogen or PTH treatment, the smoothness and porosity of endplate recovered. Compared with the Sham group, Aggrecan, Col2a and Wnt/β-catenin pathway expression in OVX group decreased, and either oestrogen or PTH treatment improved their expression. The biomechanical properties of intervertebral disc significantly changed after ovariectomy, and oestrogen or PTH treatment partly recovered them. Disc degeneration occurred with low oestrogen, and the underlying mechanisms involve nutrition supply disorders, cell type changes and decreased Wnt/β-catenin pathway activity. Oestrogen and PTH can retard disc degeneration in OVX rats and enhance Wnt/β-catenin pathway activity in nucleus pulposus. PMID:27279629

  8. The Effect of Discectomy and the Dependence on Degeneration of Human Intervertebral Disc Strain in Axial Compression

    PubMed Central

    O’Connell, Grace D.; Malhotra, Neil R.; Vresilovic, Edward J; Elliott, Dawn M.

    2011-01-01

    Study Design Biomechanics of human intervertebral discs before and after nucleotomy. Objective To noninvasively quantify the effect of nucleotomy on internal strains under axial compression in flexion, neutral, and extension positions, and to determine whether the change in strains depended on degeneration. Summary of Background Data Herniation and discectomy may accelerate the progression of disc degeneration. Removal of NP tissue has resulted in altered disc mechanics in vitro, including in a decrease in internal pressure and an increase in the deformations at physiologically relevant strains. We recently presented a technique to quantify internal disc strains using magnetic resonance imaging. Methods Degeneration was quantitatively assessed by the T1ρ relaxation in the nucleus pulposus (NP). Samples were prepared from human levels L3-L4 and/or L4-L5. A 1000N compressive load was applied while in the MR scanner. Nucleotomy was performed by removing 2g of NP through the posterior-lateral AF. The discs were rehydrated, reimaged and retested. The analyzed parameters include axial deformation, AF radial bulge and strains. Results The axial deformation was more compressive following nucleotomy. In the neutral position, the axial deformation following nucleotomy correlated with degeneration (as quantified by T1ρ in the NP), with minimal alteration in nondegenerated discs. Nucleotomy altered the radial displacements and strains in the neutral position, such that the inner AF radial bulge decreased and the radial strains were more tensile in the lateral AF and less tensile in the posterior AF. In the bending loading positions the radial strains were not affected by nucleotomy. Conclusions Nucleotomy alters the internal radial and axial AF strains in the neutral position, which may leave the AF vulnerable to damage and microfractures. In bending, the effects of nucleotomy were minimal; likely due to more of the applied load being directed over the AF. Some of the

  9. Expression of semaphorin 3A and its receptors in the human intervertebral disc: potential role in regulating neural ingrowth in the degenerate intervertebral disc

    PubMed Central

    2010-01-01

    Introduction Intervertebral disc (IVD) degeneration is considered a major underlying factor in the pathogenesis of chronic low back pain. Although the healthy IVD is both avascular and aneural, during degeneration there is ingrowth of nociceptive nerve fibres and blood vessels into proximal regions of the IVD, which may contribute to the pain. The mechanisms underlying neural ingrowth are, however, not fully understood. Semaphorin 3A (sema3A) is an axonal guidance molecule with the ability to repel nerves seeking their synaptic target. This study aimed to identify whether members of the Class 3 semaphorins were expressed by chondrocyte-like cells of the IVD addressing the hypothesis that they may play a role in repelling axons surrounding the healthy disc, thus maintaining its aneural condition. Methods Human IVD samples were investigated using reverse transcription polymerase chain reaction (RT-PCR) to identify gene expression of sema3A, 3F and their receptors: neuropilins (1 and 2) and plexins (A1-4). Sema3A protein was also localised within sections of normal and degenerate human IVD and immunopositivity quantified. Serial sections were stained using PGP9.5 and CD31 to correlate semaphorin 3A expression with nerve and blood vessel ingrowth, respectively. Results Sema3A protein was expressed highly in the healthy disc, primarily localised to the outer annulus fibrosus. In degenerate samples, sema3A expression decreased significantly in this region, although cell clusters within the degenerate nucleus pulposus exhibited strong immunopositivity. mRNA for sema3A receptors was also identified in healthy and degenerate tissues. CD31 and PGP9.5 were expressed most highly in degenerate tissues correlating with low expression of sema3A. Conclusions This study is the first to establish the expression of semaphorins and their receptors in the human IVD with a decrease seen in the degenerate painful IVD. Sema3A may therefore, amongst other roles, act as a barrier to

  10. The effect of training on lumbar spine posture and intervertebral disc degeneration in active-duty Marines.

    PubMed

    Rodriguez-Soto, Ana E; Berry, David B; Jaworski, Rebecca; Jensen, Andrew; Chung, Christine B; Niederberger, Brenda; Qadir, Aziza; Kelly, Karen R; Ward, Samuel R

    2017-08-01

    Military training aims to improve load carriage performance and reduce risk of injuries. Data describing the lumbar spine (LS) postural response to load carriage throughout training are limited. We hypothesised that training would reduce the LS postural response to load. The LS posture of 27 Marines was measured from upright MR images: with and without load (22.6 kg) at the beginning, middle, and end of School of Infantry (SOI) training. Disc degeneration was graded at L5-S1. No changes in posture and disc degeneration were found throughout training. During load carriage the LS became less lordotic and the sacrum more horizontal. Marines with disc degeneration had larger sacral postural perturbations in response to load. Our findings suggest that the postural response to load is defined more by the task needs than by the physical condition of the Marine. Practitioner Summary: The effect of military training on lumbar spine posture is unknown. The lumbar posture of 27 Marines was measured from upright MR images, with and without load throughout infantry training. No changes in posture or IVD degeneration were found across training. Marines with degeneration at the L5-S1 level had larger sacral postural perturbations in response to load.

  11. Elevated interleukin-6 expression levels are associated with intervertebral disc degeneration

    PubMed Central

    DENG, XIAO; ZHAO, FENG; KANG, BAOLIN; ZHANG, XIN

    2016-01-01

    The present study aimed to investigate whether serum interleukin-6 (IL-6) expression levels were associated with the onset and progression of intervertebral disc degeneration (IDD). A comprehensive meta-analysis of the scientific literature from numerous electronic databases was performed, in order to obtain published studies associated with the topic of interest. Relevant case-control studies that had previously assessed a correlation between IL-6 expression levels and IDD were identified using predetermined inclusion and exclusion criteria. The STATA version 12.0 software was used for statistical analysis of the extracted data. A total of 112 studies were initially retrieved, with eight studies meeting the inclusion criteria. These contained a total of 392 subjects, of which 263 were patients with IDD and 129 were healthy controls. A meta-analysis of the eight studies demonstrated that serum IL-6 protein expression levels may be associated with IDD, and this was irrespective of IDD subtype (bulging, protrusion, or sequestration). Notably, serum expression levels of the IL-6 protein were upregulated in intervertebral disc (IVD) protrusion tissue, as compared with normal IVD tissue; thus suggesting that IL-6 may have an important role in the pathophysiological process of IDD. PMID:27073460

  12. Acidic pH promotes intervertebral disc degeneration: Acid-sensing ion channel -3 as a potential therapeutic target

    PubMed Central

    Gilbert, Hamish T. J.; Hodson, Nathan; Baird, Pauline; Richardson, Stephen M.; Hoyland, Judith A.

    2016-01-01

    The aetiology of intervertebral disc (IVD) degeneration remains poorly understood. Painful IVD degeneration is associated with an acidic intradiscal pH but the response of NP cells to this aberrant microenvironmental factor remains to be fully characterised. The aim here was to address the hypothesis that acidic pH, similar to that found in degenerate IVDs, leads to the altered cell/functional phenotype observed during IVD degeneration, and to investigate the involvement of acid-sensing ion channel (ASIC) -3 in the response. Human NP cells were treated with a range of pH, from that of a non-degenerate (pH 7.4 and 7.1) through to mildly degenerate (pH 6.8) and severely degenerate IVD (pH 6.5 and 6.2). Increasing acidity of pH caused a decrease in cell proliferation and viability, a shift towards matrix catabolism and increased expression of proinflammatory cytokines and pain-related factors. Acidic pH resulted in an increase in ASIC-3 expression. Importantly, inhibition of ASIC-3 prevented the acidic pH induced proinflammatory and pain-related phenotype in NP cells. Acidic pH causes a catabolic and degenerate phenotype in NP cells which is inhibited by blocking ASIC-3 activity, suggesting that this may be a useful therapeutic target for treatment of IVD degeneration. PMID:27853274

  13. An organ culture system to model early degenerative changes of the intervertebral disc II: profiling global gene expression changes.

    PubMed

    Markova, Dessislava Z; Kepler, Christopher K; Addya, Sankar; Murray, Hallie B; Vaccaro, Alexander R; Shapiro, Irving M; Anderson, D Greg; Albert, Todd J; Risbud, Makarand V

    2013-01-01

    Despite many advances in our understanding of the molecular basis of disc degeneration, there remains a paucity of preclinical models which can be used to study the biochemical and molecular events that drive disc degeneration, and the effects of potential therapeutic interventions. The goal of this study is to characterize global gene expression changes in a disc organ culture system that mimics early nontraumatic disc degeneration. To mimic a degenerative insult, rat intervertebral discs were cultured in the presence of TNF-α, IL-1β and serum-limiting conditions. Gene expression analysis was performed using a microarray to identify differential gene expression between experimental and control groups. Differential pattern of gene expression was confirmed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) or Western blot. Treatment resulted in significant changes in expression of more than 1,000 genes affecting many aspects of cell function including cellular movement, the cell cycle, cellular development, and cell death and proliferation. Many of the most highly upregulated and downregulated genes have known functions in disc degeneration and extracellular matrix hemostasis. Construction of gene networks based on known cellular pathways and expression data from our analysis demonstrated that the network associated with cell death, cell cycle regulation and DNA replication and repair was most heavily affected in this model of disc degeneration. This rat organ culture model uses cytokine exposure to induce wide gene expression changes with the most affected genes having known reported functions in disc degeneration. We propose that this model is a valuable tool to study the etiology of disc degeneration and evaluate potential therapeutic treatments.

  14. An organ culture system to model early degenerative changes of the intervertebral disc II: profiling global gene expression changes

    PubMed Central

    2013-01-01

    Introduction Despite many advances in our understanding of the molecular basis of disc degeneration, there remains a paucity of preclinical models which can be used to study the biochemical and molecular events that drive disc degeneration, and the effects of potential therapeutic interventions. The goal of this study is to characterize global gene expression changes in a disc organ culture system that mimics early nontraumatic disc degeneration. Methods To mimic a degenerative insult, rat intervertebral discs were cultured in the presence of TNF-α, IL-1β and serum-limiting conditions. Gene expression analysis was performed using a microarray to identify differential gene expression between experimental and control groups. Differential pattern of gene expression was confirmed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) or Western blot. Results Treatment resulted in significant changes in expression of more than 1,000 genes affecting many aspects of cell function including cellular movement, the cell cycle, cellular development, and cell death and proliferation. Many of the most highly upregulated and downregulated genes have known functions in disc degeneration and extracellular matrix hemostasis. Construction of gene networks based on known cellular pathways and expression data from our analysis demonstrated that the network associated with cell death, cell cycle regulation and DNA replication and repair was most heavily affected in this model of disc degeneration. Conclusions This rat organ culture model uses cytokine exposure to induce wide gene expression changes with the most affected genes having known reported functions in disc degeneration. We propose that this model is a valuable tool to study the etiology of disc degeneration and evaluate potential therapeutic treatments. PMID:24171898

  15. MyD88-dependent Toll-like receptor 4 signal pathway in intervertebral disc degeneration

    PubMed Central

    Qin, Chuqiang; Zhang, Bo; Zhang, Liang; Zhang, Zhi; Wang, Le; Tang, Long; Li, Shuangqing; Yang, Yixi; Yang, Fuguo; Zhang, Ping; Yang, Bo

    2016-01-01

    Lower back pain (LBP) is a common and remitting problem. One of the primary causes of LBP is thought to be degeneration of the intervertebral disc (IVD). The aim of the present study was to investigate the role of the myeloid differentiation primary-response protein 88 (MyD88)-dependent Toll-like receptor 4 (TLR4) signal pathway in the mechanism of IVD degeneration. IVD nucleus pulposus cells isolated and cultured from the lumbar vertebrae of Wistar rats were stimulated by various doses of lipopolysaccharide (LPS; 0.1, 1, 10 and 100 µg/ml) to simulate IVD degeneration. Cells were rinsed and cultured in serum-free Dulbecco's modified Eagle's medium/F12. Reverse transcription-quantitative polymerase chain reaction was used to determine the levels of TLR4, MyD88, tumor necrosis factor α (TNFα), and interleukin-1β (IL-1β) mRNA expression after 1, 3, 6, 9 and 12 h of incubation. Additionally, western blot and enzyme-linked immunosorbent assay analyses were used to determine the levels of TLR4, MyD88, TNFα, and IL-1β protein expression after 24, 48 and 72 h of incubation. The levels of TLR4, MyD88, TNFα and IL-1β mRNA all increased in the cells stimulated by 10 µg/ml LPS at 3, 6 and 9 h (all P<0.001). Furthermore, the levels of TLR4, MyD88, TNFα and IL-1β protein all increased at 24, 48 and 72 h (all P<0.001). Additionally, the mRNA and protein levels of TLR4, MyD88, TNFα and IL-1β increased significantly in the cells stimulated by 1, 10 and 100 µg/ml LPS compared with the control group, and reached a peak in the 10 µg/ml LPS group (all P<0.001). These results suggest that the MyD88-dependent TLR4 signal pathway is a target pathway in IVD degeneration. This pathway is time phase- and dose-dependent, and when activated can lead to the release of inflammatory factors that participate in IVD degeneration. PMID:27446251

  16. Enhancement of Lumbar Fusion and Alleviation of Adjacent Segment Disc Degeneration by Intermittent PTH(1-34) in Ovariectomized Rats.

    PubMed

    Zhou, Zhuang; Tian, Fa-Ming; Gou, Yu; Wang, Peng; Zhang, Heng; Song, Hui-Ping; Shen, Yong; Zhang, Ying-Ze; Zhang, Liu

    2016-04-01

    Osteoporosis, which is prevalent in postmenopausal or aged populations, is thought to be a contributing factor to adjacent segment disc degeneration (ASDD), and the incidence and extent of ASDD may be augmented by osteopenia. Parathyroid hormone (PTH) (1-34) has already been shown to be beneficial in osteoporosis, lumbar fusion and matrix homeostasis of intervertebral discs. However, whether PTH(1-34) has a reversing or retarding effect on ASDD in osteopenia has not been confirmed. In the present study, we evaluated the effects of intermittent PTH(1-34) on ASDD in an ovariectomized (OVX) rat model. One hundred 3-month-old female Sprague-Dawley rats underwent L4 -L5 posterolateral lumbar fusion (PLF) with spinous-process wire fixation 4 weeks after OVX surgery. Control groups were established accordingly. PTH(1-34) was intermittently administered immediately after PLF surgery and lasted for 8 weeks using the following groups (n = 20) (V = vehicle): Sham+V, OVX+V, Sham+PLF+V, OVX+PLF+V, OVX+PLF+PTH. The fused segments showed clear evidence of eliminated motion on the fusion-segment based on manual palpation. Greater new bone formation in histology was observed in PTH-treated animals compared to the control group. The extent of ASDD was significantly increased by ovariotomy. Intermittent PTH(1-34) significantly alleviated ASDD by preserving disc height, microvessel density, relative area of vascular buds, endplate thickness and the relative area of endplate calcification. Moreover, protein expression results showed that PTH(1-34) not only inhibited matrix degradation by decreasing MMP-13, ADAMTS-4 and Col-I, but also promote matrix synthesis by increasing Col-II and Aggrecan. In conclusion, PTH(1-34), which effectively improves lumbar fusion and alleviates ASDD in ovariectomized rats, may be a potential candidate to ameliorate the prognosis of lumbar fusion in osteopenia. © 2015 American Society for Bone and Mineral Research.

  17. Growth factor expression in degenerated intervertebral disc tissue. An immunohistochemical analysis of transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor.

    PubMed

    Tolonen, Jukka; Grönblad, Mats; Vanharanta, Heikki; Virri, Johanna; Guyer, Richard D; Rytömaa, Tapio; Karaharju, Erkki O

    2006-05-01

    Degenerated intervertebral disc has lost its normal architecture, and there are changes both in the nuclear and annular parts of the disc. Changes in cell shape, especially in the annulus fibrosus, have been reported. During degeneration the cells become more rounded, chondrocyte-like, whereas in the normal condition annular cells are more spindle shaped. These chondrocyte-like cells, often forming clusters, affect extracellular matrix turnover. In previous studies transforming growth factor beta (TGFbeta) -1 and -2, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) have been highlighted in herniated intervertebral disc tissue. In the present study the same growth factors are analysed immunohistochemically in degenerated intervertebral disc tissue. Disc material was obtained from 16 discs operated for painful degenerative disc disease. Discs were classified according to the Dallas Discogram Description. Different disc regions were analysed in parallel. As normal control disc tissue material from eight organ donors was used. Polyclonal antibodies against different growth factors and TGFbeta receptor type II were used, and the immunoreaction was detected by the avidin biotin complex method. All studied degenerated discs showed immunoreactivity for TGFbeta receptor type II and bFGF. Fifteen of 16 discs were immunopositive for TGFbeta-1 and -2, respectively, and none showed immunoreaction for PDGF. Immunopositivity was located in blood vessels and in disc cells. In the nucleus pulposus the immunoreaction was located almost exclusively in chondrocyte-like disc cells, whereas in the annular region this reaction was either in chondrocyte-like disc cells, often forming clusters, or in fibroblast-like disc cells. Chondrocyte-like disc cells were especially prevalent in the posterior disrupted area. In the anterior area of the annulus fibrosus the distribution was more even between these two cell types. bFGF was expressed in the anterior annulus

  18. An In Vivo Model of Reduced Nucleus Pulposus Glycosaminoglycan Content in the Rat Lumbar Intervertebral Disc

    PubMed Central

    Boxberger, John I.; Auerbach, Joshua D.; Sen, Sounok; Elliott, Dawn M.

    2009-01-01

    Study Design An in vivo model resembling early stage disc degeneration in the rat lumbar spine. Objective Simulate the reduced glycosaminoglycan content and altered mechanics observed in intervertebral disc degeneration using a controlled injection of chondroitinase ABC (ChABC). Summary of Background Data Nucleus glycosaminoglycan reduction occurs early during disc degeneration; however, mechanisms through which degeneration progresses from this state are unknown. Animal models simulating this condition are essential for understanding disease progression and for development of therapies aimed at early intervention. Methods ChABC was injected into the nucleus pulposus, and discs were evaluated via micro-CT, mechanical testing, biochemical assays, and histology 4 and 12 weeks after injection. Results At 4 weeks, reductions in nucleus glycosaminoglycan level by 43%, average height by 12%, neutral zone modulus by 40%, and increases in range of motion by 40%, and creep strain by 25% were found. Neutral zone modulus and range of motion were correlated with nucleus glycosaminoglycan. At 12 weeks, recovery of some mechanical function was detected as range of motion and creep returned to control levels; however, this was not attributed to glycosaminoglycan restoration, because mechanics were no longer correlated with glycosaminoglycan. Conclusion An in vivo model simulating physiologic levels of glycosaminoglycan loss was created to aid in understanding the relationships between altered biochemistry, altered mechanics, and altered cellular function in degeneration. PMID:18197098

  19. Early stage disc degeneration does not have an appreciable affect on stiffness and load transfer following vertebroplasty and kyphoplasty

    PubMed Central

    Keller, Tony S.; Schizas, Constantin

    2008-01-01

    Vertebroplasty and kyphoplasty have been reported to alter the mechanical behavior of the treated and adjacent-level segments, and have been suggested to increase the risk for adjacent-level fractures. The intervertebral disc (IVD) plays an important role in the mechanical behavior of vertebral motion segments. Comparisons between normal and degenerative IVD motion segments following cement augmentation have yet to be reported. A microstructural finite element model of a degenerative IVD motion segment was constructed from micro-CT images. Microdamage within the vertebral body trabecular structure was used to simulate a slightly (I = 83.5% of intact stiffness), moderately (II = 57.8% of intact stiffness), and severely (III = 16.0% of intact stiffness) damaged motion segment. Six variable geometry single-segment cement repair strategies (models A–F) were studied at each damage level (I–III). IVD and bone stresses, and motion segment stiffness, were compared with the intact and baseline damage models (untreated), as well as, previous findings using normal IVD models with the same repair strategies. Overall, small differences were observed in motion segment stiffness and average stresses between the degenerative and normal disc repair models. We did however observe a reduction in endplate bulge and a redistribution in the microstructural tissue level stresses across both endplates and in the treated segment following early stage IVD degeneration. The cement augmentation strategy placing bone cement along the periphery of the vertebra (model E) proved to be the most advantageous in treating the degenerative IVD models by showing larger reductions in the average bone stresses (vertebral and endplate) as compared to the normal IVD models. Furthermore, only this repair strategy, and the complete cement fill strategy (model F), were able to restore the slightly damaged (I) motion segment stiffness above pre-damaged (intact) levels. Early stage IVD degeneration

  20. Dynamical modelling of galactic disc outskirts

    NASA Astrophysics Data System (ADS)

    Athanassoula, E.

    2017-03-01

    I review briefly some dynamical models of structures in the outer parts of disc galaxies, including models of polar rings, tidal tails and bridges. I then discuss the density distribution in the outer parts of discs. For this, I compare observations to results of a model in which the disc galaxy is in fact the remnant of a major merger, and find good agreement. This comparison includes radial profiles of the projected surface density and of stellar age, as well as time evolution of the break radius and of the inner and outer disc scale lengths. I also compare the radial projected surface density profiles of dynamically motivated mono-age populations and find that, compared to older populations, younger ones have flatter density profiles in the inner region and steeper in the outer one. The break radius, however, does not vary with stellar age, again in good agreement with observations.

  1. Influence of age and gender on thoracic vertebral body shape and disc degeneration: an MR investigation of 169 cases

    PubMed Central

    GOH, S.; TAN, C.; PRICE, R. I.; EDMONDSTON, S. J.; SONG, S.; DAVIS, S.; SINGER, K. P.

    2000-01-01

    There are limited data detailing the pattern of age and gender-related changes to the thoracic vertebral bodies and intervertebral discs. A retrospective MR investigation, involving T1-weighted midsagittal images from 169 cases, was undertaken to examine age influences on the anterior wedge (anteroposterior height ratio or Ha/Hp), biconcavity (midposterior height ratio or Hm/Hp), and compression indices (posterior height/anteroposterior diameter or Hp/D) of the thoracic vertebral bodies. Disc degenerative changes in the annulus, nucleus, end-plate and disc margin were noted on T2-weighted sagittal images for the 169 cases, based on a 3-level grading system. A linear age-related decline in the Ha/Hp and Hm/Hp indices was noted. The Hp/D index increased during the first few decades of life, then decreased gradually thereafter. The prevalence of abnormal findings in the annuli, nuclei and disc margins increased with increasing age, particularly in the mid and lower thoracic discs. Greater disc degenerative changes were observed in males. These findings provide further insight into the nature of thoracic vertebral shape changes across the lifespan, and the typical patterns of degeneration of the thoracic intervertebral discs. PMID:11197538

  2. Apoptosis, senescence, and autophagy in rat nucleus pulposus cells: Implications for diabetic intervertebral disc degeneration.

    PubMed

    Jiang, Libo; Zhang, Xiaolei; Zheng, Xuhao; Ru, Ao; Ni, Xiao; Wu, Yaosen; Tian, Naifeng; Huang, Yixing; Xue, Enxing; Wang, Xiangyang; Xu, Huazi

    2013-05-01

    This research was aimed to study the mechanisms by which diabetes aggravates intervertebral disc degeneration (IDD) and to discuss the relationship between autophagy and IDD in nucleus pulposus (NP) cells. Sixteen weeks after injecting streptozotocin (STZ), the intervertebral discs (IVDs) were studied by histology, Alcian blue, 1,9-dimethylmethylene blue (DMMB), immunohistochemistry, and RT-PCR to explore the IDD. The apoptosis and senescence of NP cells was investigated by terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay, immunohistochemistry, and Western blot for caspase3, caspase8, caspase9, and p16lnk4A (increased in cellular senescence). The level of autophagy in NP cells was detected by Western blot, immunohistochemistry, and transmission electron microscopy (TEM). The proteoglycan and collagen II in the extracellular matrix and the aggrecan and collagen II mRNA expression in NP cells of diabetic rats were decreased compared with the control group. Diabetes increased apoptosis of NP cells and led to activations of initiators of intrinsic (caspases-9) and extrinsic (caspase-8) pathways as well as their common executioner (caspase-3). Cellular senescence was increased about twofold in NP of diabetic rats. In addition, the Western blot, immunohistochemistry, and TEM demonstrated higher level of autophagy in NP cells of diabetic rats than control rats to a statistically significant extent. These findings support that diabetes induced by STZ can cause IDD by accelerating the apoptosis and senescence of NP cells excluding the overweight influence. And the results suggest that the autophagy may be a response mechanism to the change of NP cells in diabetic rats. Copyright © 2012 Orthopaedic Research Society.

  3. Resistin Promotes Intervertebral Disc Degeneration by Upregulation of ADAMTS-5 Through p38 MAPK Signaling Pathway.

    PubMed

    Liu, Caijun; Yang, Hao; Gao, Fei; Li, Xiang; An, Yan; Wang, Jianru; Jin, Anmin

    2016-09-15

    Rat nucleus pulposus (NP) cells were activated with resistin with or without p38 mitogen-activated protein kinase (MAPK) pathway inhibition. The expression of a disintegrin and metalloprotease with thrombospondin motif-5 (ADAMTS-5), which plays an important role in intervertebral disc degeneration (IDD), was determined. The aim of this study was to demonstrate whether resistin can influence the ADAMTS-5 expression and to further investigate the underlying mechanisms. Obesity has been demonstrated to promote IDD, whereas the exact mechanism remains poorly understood. Resistin, as an important adipokine, is increased with obesity and has been shown to play pro-inflammatory and catabolic role in cartilage metabolism. However, the effect of resistin on the catabolic enzymes within NP cells remains unknown. We exposed NP cells to resistin, and the transcriptional activity, gene expression, and protein levels of ADAMTS-5 were measured by luciferase reporter assay, qRT-polymerase chain reaction, immunofluorescence, and western blot, respectively. The activation of p38 MAPK pathways was detected using western blot analysis. Resistin had no effect on cell viability. Resistin increased ADAMTS-5 expression in rat NP cells time and dose dependently. The p38 MAPK signaling pathway was activated after exposure to resistin. Treatment with p38 inhibitor decreased the upregulation of ADAMTS-5 by resistin. The current study, for the first time, investigated the role of resistin in ADAMTS-5 regulation in IDD. These findings provide novel evidence supporting the causative role of obesity in IDD, which is important to develop novel preventative or therapeutic treatment in disc degenerative disorders. N/A.

  4. Impact of T1 slope on surgical and adjacent segment degeneration after Bryan cervical disc arthroplasty.

    PubMed

    Yang, Peng; Li, Yongqian; Li, Jia; Shen, Yong

    2017-01-01

    This retrospective study investigated an association between preoperative T1 slope and surgical and adjacent segment degeneration (SASD) after Bryan cervical disc arthroplasty (BCDA) in patients with cervical degenerative disc disease. Based on preoperative standing lateral radiographs, 90 patients were classified according to T1 slope that was higher or lower than the 50th percentile (high T1 or low T1, 28 and 62 patients, respectively). Patients were also classified as SASD or non-SASD (38 and 52 patients, respectively) determined by radiographs at final follow-up. Visual analog scale (VAS) and Neck Disability Index (NDI) scores for neck and arm pain were noted, and changes in the sagittal alignment of the cervical spine (SACS), functional spinal unit (FSU) angle, and FSU range of motion (ROM) were also noted. Univariate and multivariate logistic regression analyses were performed to determine the risk factors for SASD. The overall rate of SASD was 42.2% (38/90). The SACS, FSU angle, FSU ROM, and SASD rates of the high T1 and low T1 slope groups were significantly different at the last follow-up. The NDI and VAS scores of the high T1 slope group were significantly greater than those of the low T1 slope. The multivariate logistic regression analysis showed that high T1 slope and endplate coverage discrepancy (ie, residual space behind the prosthesis) were significant risk factors for SASD after BCDA. High T1 slope and endplate coverage discrepancy were associated with SASD after BCDA. Patients with a high preoperative T1 slope have a smaller FSU angle and more neck pain after BCDA.

  5. The Relation Between Sacral Angle and Vertical Angle of Sacral Curvature and Lumbar Disc Degeneration

    PubMed Central

    Ghasemi, Ahmad; Haddadi, Kaveh; Khoshakhlagh, Mohammad; Ganjeh, Hamid Reza

    2016-01-01

    Abstract The purpose of this study is to determine the reliability and validity of a goniometric measurement of the vertical angle of the sacrum and sacral angle (SA), and their relationships to lumbar degeneration. A herniated lumbar disc is one of the most frequent medical issues. Investigators in a number of studies have reported associated risk factors for prevalent disc degeneration. Atypical lumbosacral angles and curvature are thought to contribute to the degradation of the spine by many researchers. This study analyzed 360 patients referred to our clinic from 2013 to 2015 due to low back pain. A cross-sectional case–control study was designed in order to compare the sagittal alignment of the lumbosacral area in 3 groups of patients suffering from LBP. A total 120 patients were in a control group with a normal lumbar magnetic resonance imaging (MRI), 120 patients had lumbar disk herniation (LDH), and 120 patients had spinal stenosis. From the sagittal plan of lumbar MRI, SA and vertical angle of sacral curvature (VASC) were determined and then analyzed. The means of VASC in these groups were: 38.98 (SD: 6.36 ± 0.58), 40.89 (SD: 7.69 ± 0.69), and 40.54 (SD: 7.13 ± 0.92), respectively (P = 0.089). Moreover, studies of SA in 3 groups showed that the means of SA were: 39.30 (SD: 6.69 ± 0.63), 40.52 (SD: 7.47 ± 0.65), and 35.63 (SD: 6.07 ± 0.79), respectively. Relation between SA and spinal stenosis was just statistically significant (P ≤ 0.05). One significant limitation of our study is the lack of standing MRI for increased accuracy of measurement. However, we were reluctant to give patients needless exposure to radiation from conventional X-ray, and instead used MRI scans. We did not find any significant correlation between the VASC and LDH in lumbar MRI. Also, SA is not an independent risk factor for LDH in men and women. We suggested that there are several biomechanical factors involved in LDH. PMID:26871821

  6. Changes in gene expression and protein distribution at different stages of mechanically induced disc degeneration--an in vivo study on the New Zealand white rabbit.

    PubMed

    Omlor, Georg W; Lorenz, Helga; Engelleiter, Karl; Richter, Wiltrud; Carstens, Claus; Kroeber, Markus W; Guehring, Thorsten

    2006-03-01

    The objective of the study was to improve the biological understanding of degenerative disc disease using a rabbit model in which different stages of disc degeneration are induced by variation of the duration of loading with an external compression-device applying 2.4 MPa. Gene expression and protein distribution were analyzed in controls and after 1, 28, and 56 days of hyperphysiologic loading. To evaluate extracellular matrix genes, quantitative real-time reverse-transcriptase polymerase chain reaction was applied for collagen I, collagen II, biglycan, decorin, fibromodulin, fibronectin, aggrecan, and osteonectin. As representatives of catabolic, anticatabolic, and anabolic factors, matrix metalloproteinase-13 (MMP-13), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and bone morphogenetic protein-2 (BMP-2) were chosen. To evaluate protein distribution, immunohistochemistry was performed for collagen I, collagen II, and BMP-2/4. Matrix gene expression was characterized by two major developments: collagen I and II, biglycan, and decorin showed early elevation followed by later downregulation to control levels, whereas fibromodulin, fibronectin, aggrecan, and osteonectin showed continuous upregulation or remained at similar levels. Induction of MMP-13 gene expression was found in degenerated discs. TIMP-1 and BMP-2 were elevated immediately after hyperphysiologic loading and presented highest levels in the 56-day group. Immunohistochemistry showed less collagen II and BMP-2/4 positive cells after compression. In conclusion, elevated matrix gene expression represents an early cellular response to hyperphysiologic loading. As degeneration progresses, some matrix genes increase upregulation, whereas others start downregulation. Continuous upregulation of catabolic, anticatabolic, and anabolic factors indicates their important role in the degeneration process. Copyright 2005 Orthopaedic Research Society.

  7. The Effects of Age, Gender, Ethnicity, and Spinal Level on the Rate of Intervertebral Disc Degeneration. A review of 1712 Intervertebral Discs

    PubMed Central

    Siemionow, Krzysztof; An, Howard; Masuda, Koichi; Andersson, Gunnar; Cs-Szabo, Gabriella

    2010-01-01

    Study Design A gross anatomical and magnetic resonance imaging (MRI) study of intervertebral disc (IVD) degeneration in fresh cadaveric lumbar spines. Objective The purpose of this study was to find the rate of IVD degeneration. Summary of Background Data Age, sex, race, and lumbar level are among some of the factors that play a role in IVD degeneration. The rate at which IVDs degenerate is unknown. Methods Complete lumbar spine segments (T11/12 to S1) were received within 24 hours of death. The nucleus pulposus, annulus fibrosus, cartilaginous and bony end-plate, and the peripheral verterbral body were assessed with MRI and IVD degeneration was graded by two observers from grade 1(nondegenerated) to grade 5(severely degenerated) based on a scale developed by Tanaka et al. The specimens were then sectioned and gross anatomical evaluation was performed according to Thompson et al. Results 433 donors and 1712 IVDs were analyzed. There were 366 Caucasians, 47 Africans, 16 Hispanics, 4 Asian. There were 306 males and 127 females. The age range was 14–81 years, (average 60.5+/−11.3). For donors greater than age 40, the L5/S1 IVD degenerated at a significantly faster rate of 0.043/year compared to 0.031, 0.034, 0.033, 0.027 for L12, L23, L34, L45, respectively. For donors younger than 40, L5/S1 IVD degenerated at a significantly faster rate of 0.141/year compared to 0.033,0.021, 0.031, 0.050 for L12, L23, L34, L45, respectively. Multiple regression analysis revealed that gender had no significant effect on IVD degeneration whereas African ethnicity was associated with lower Thompson score at L12, L23, L34, L45 when compared to Caucasians. Conclusions The relatively early degeneration at L5-S1 in all races and lower Thompson grade in donors of African ethnicity needs further investigation. Factors such as sagittal alignment, facet joint arthritis, and genetics potentially play a role in IVD degeneration. PMID:21217432

  8. Interleukin 1 Polymorphisms Contribute to Intervertebral Disc Degeneration Risk: A Meta-Analysis

    PubMed Central

    Fu, Changfeng; Xu, Feng; Chen, Yong; Wang, Zhenyu; Liu, Yi

    2016-01-01

    Objective We performed a meta-analysis to assess association between interleukin 1 (IL-1) polymorphisms and the risk of Intervertebral Disc Degeneration (IDD). Background A series of studies have investigated the association between common single nucleotide polymorphisms in IL-1 and IDD risk; however, the overall results are inconclusive. Methods Two independent investigators conducted a systematic search for relevant available studies. Allele frequencies were extracted from each study. The association between the IL-1α (+889C/T) or IL-1β (+3954C/T) polymorphism and IDD risk was measured by odds ratios (OR) with 95% confidence intervals (95% CI). Results Five and six studies, respectively, were ultimately included in the meta-analysis for the IL-1α (+889C/T) and IL-1β (+3954C/T) polymorphism. The combined results showed that the IL-1α (+889C/T) polymorphism was significantly associated with increased susceptibility to IDD, particularly in Caucasians (TT versus CC: OR = 2.95, 95% CI: 1.45, 6.04; Pheterogeneity = 0.82; TT versus CC/CT: OR = 2.29, 95% CI: 1.18, 4.47; Pheterogeneity = 0.20). In contrast, the IL-1β (+3954C/T) polymorphism showed a trend towards increased risk in Caucasians but no association in Asians. Conclusion This meta-analysis suggested that the IL-1α (+889C/T) polymorphism is significantly associated with risk of IDD, especially in Caucasian populations. PMID:27253397

  9. Genome-Wide Identification of Long Noncoding RNAs in Human Intervertebral Disc Degeneration by RNA Sequencing

    PubMed Central

    Zhao, Bo; Lu, Minjuan; Wang, Dong; Li, Haopeng

    2016-01-01

    Long noncoding RNAs (lncRNAs) are emerging as crucial players in a myriad of biological processes. However, the precise mechanism and functions of most lncRNAs are poorly characterized. In this study, we presented genome-wide identification of lncRNAs in the patients with intervertebral disc degeneration (IDD) and spinal cord injury (control) using RNA sequencing (RNA-seq). A total of 124.6 million raw reads were yielded using Hiseq 2500 platform and approximately 88% clean reads could be aligned to human reference genome in both IDD and control groups. RNA-seq profiling indicated that 1,854 lncRNAs were differentially expressed (log2 fold change ≥ 1 or ≤−1, p < 0.05), in which 1,530 could potentially target 6,386 genes via cis-regulatory effects. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for these target genes suggested that lncRNAs were involved in diverse pathways, such as lysosome, focal adhesion, and MAPK signaling. In addition, a competing endogenous RNA (ceRNA) network was constructed for analyzing the function of lncRNAs. Further, quantitative real time PCR (qRT-PCR) was used to confirm the differentially expressed lncRNAs and ceRNA network. In conclusion, our results present the first global identification of lncRNAs in IDD and may provide candidate diagnostic biomarkers for IDD treatment. PMID:28097131

  10. Interleukin 1 Polymorphisms Contribute to Intervertebral Disc Degeneration Risk: A Meta-Analysis.

    PubMed

    Wang, Zheng; Qu, Zhigang; Fu, Changfeng; Xu, Feng; Chen, Yong; Wang, Zhenyu; Liu, Yi

    2016-01-01

    We performed a meta-analysis to assess association between interleukin 1 (IL-1) polymorphisms and the risk of Intervertebral Disc Degeneration (IDD). A series of studies have investigated the association between common single nucleotide polymorphisms in IL-1 and IDD risk; however, the overall results are inconclusive. Two independent investigators conducted a systematic search for relevant available studies. Allele frequencies were extracted from each study. The association between the IL-1α (+889C/T) or IL-1β (+3954C/T) polymorphism and IDD risk was measured by odds ratios (OR) with 95% confidence intervals (95% CI). Five and six studies, respectively, were ultimately included in the meta-analysis for the IL-1α (+889C/T) and IL-1β (+3954C/T) polymorphism. The combined results showed that the IL-1α (+889C/T) polymorphism was significantly associated with increased susceptibility to IDD, particularly in Caucasians (TT versus CC: OR = 2.95, 95% CI: 1.45, 6.04; Pheterogeneity = 0.82; TT versus OR = 2.29, 95% CI: 1.18, 4.47; Pheterogeneity = 0.20). In contrast, the IL-1β (+3954C/T) polymorphism showed a trend towards increased risk in Caucasians but no association in Asians. This meta-analysis suggested that the IL-1α (+889C/T) polymorphism is significantly associated with risk of IDD, especially in Caucasian populations.

  11. Stem Cell Therapies for Intervertebral Disc Degeneration: Immune Privilege Reinforcement by Fas/FasL Regulating Machinery.

    PubMed

    Ma, Chi-Jiao; Liu, Xu; Che, Lu; Liu, Zhi-Heng; Samartzis, Dino; Wang, Hai-Qiang

    2015-01-01

    As a main contributing factor to low back pain, intervertebral disc degeneration (IDD) is the fundamental basis for various debilitating spinal diseases. The pros and cons of current treatment modalities necessitate biological treatment strategies targeting for reversing or altering the degeneration process in terms of molecules or genes. The advances in stem cell research facilitate the studies aiming for possible clinical application of stem cell therapies for IDD. Human NP cells are versatile with cell morphology full of variety, capable of synthesizing extracellular matrix components, engulfing substances by autophagy and phagocytosis, mitochondrial vacuolization indicating dysfunction, expressing Fas and FasL as significant omens of immune privileged sites. Human discs belong to immune privilege organs with functional FasL expression, which can interact with invasive immune cells by Fas-FasL regulatory machinery. IDD is characterized by decreased expression level of FasL with dysfunctional FasL, which in turn unbalances the interaction between NP cells and immune cells. Certain modulation factors might play a role in the process, such as miR-155. Accumulating evidence indicates that Fas-FasL network expresses in a variety of stem cells. Given the expression of functional FasL and insensitive Fas in stem cells (we term as FasL privilege), transplantation of stem cells into the disc may regenerate the degenerative disc by not only differentiating into NP-like cells, increasing extracellular matrix, but also reinforce immune privilege via interaction with immune cells by Fas-FasL network.

  12. TGFβ and BMP Dependent Cell Fate Changes Due to Loss of Filamin B Produces Disc Degeneration and Progressive Vertebral Fusions

    PubMed Central

    Zieba, Jennifer; Forlenza, Kimberly Nicole; Khatra, Jagteshwar Singh; Sarukhanov, Anna; Duran, Ivan; Rigueur, Diana; Lyons, Karen M.; Cohn, Daniel H.; Merrill, Amy E.; Krakow, Deborah

    2016-01-01

    Spondylocarpotarsal synostosis (SCT) is an autosomal recessive disorder characterized by progressive vertebral fusions and caused by loss of function mutations in Filamin B (FLNB). FLNB acts as a signaling scaffold by linking the actin cytoskleteon to signal transduction systems, yet the disease mechanisms for SCT remain unclear. Employing a Flnb knockout mouse, we found morphologic and molecular evidence that the intervertebral discs (IVDs) of Flnb–/–mice undergo rapid and progressive degeneration during postnatal development as a result of abnormal cell fate changes in the IVD, particularly the annulus fibrosus (AF). In Flnb–/–mice, the AF cells lose their typical fibroblast-like characteristics and acquire the molecular and phenotypic signature of hypertrophic chondrocytes. This change is characterized by hallmarks of endochondral-like ossification including alterations in collagen matrix, expression of Collagen X, increased apoptosis, and inappropriate ossification of the disc tissue. We show that conversion of the AF cells into chondrocytes is coincident with upregulated TGFβ signaling via Smad2/3 and BMP induced p38 signaling as well as sustained activation of canonical and noncanonical target genes p21 and Ctgf. These findings indicate that FLNB is involved in attenuation of TGFβ/BMP signaling and influences AF cell fate. Furthermore, we demonstrate that the IVD disruptions in Flnb–/–mice resemble aging degenerative discs and reveal new insights into the molecular causes of vertebral fusions and disc degeneration. PMID:27019229

  13. Debris Discs: Modeling/theory review

    NASA Astrophysics Data System (ADS)

    Thébault, P.

    2012-03-01

    An impressive amount of photometric, spectroscopic and imaging observations of circumstellar debris discs has been accumulated over the past 3 decades, revealing that they come in all shapes and flavours, from young post-planet-formation systems like Beta-Pic to much older ones like Vega. What we see in these systems are small grains, which are probably only the tip of the iceberg of a vast population of larger (undetectable) collisionally-eroding bodies, leftover from the planet-formation process. Understanding the spatial structure, physical properties, origin and evolution of this dust is of crucial importance, as it is our only window into what is going on in these systems. Dust can be used as a tracer of the distribution of their collisional progenitors and of possible hidden massive pertubers, but can also allow to derive valuable information about the disc's total mass, size distribution or chemical composition. I will review the state of the art in numerical models of debris disc, and present some important issues that are explored by current modelling efforts: planet-disc interactions, link between cold (i.e. Herschel-observed) and hot discs, effect of binarity, transient versus continuous processes, etc. I will finally present some possible perspectives for the development of future models.

  14. Retinal Cell Degeneration in Animal Models

    PubMed Central

    Niwa, Masayuki; Aoki, Hitomi; Hirata, Akihiro; Tomita, Hiroyuki; Green, Paul G.; Hara, Akira

    2016-01-01

    The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl2-induced), autoimmune (experimental autoimmune encephalomyelitis), mechanical stress (optic nerve crush-induced, light-induced) and ischemia (transient retinal ischemia-induced). The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage. PMID:26784179

  15. Vitamin D Receptor Gene, Matrix Metalloproteinase 3 Polymorphisms and the Risk of Intervertebral Disc Degeneration Susceptibility: Meta-Analysis

    PubMed Central

    Huang, Yongjing; Zhao, Shujie; Xu, Nanwei

    2016-01-01

    Several studies have evaluated the association between vitamin D receptor, matrix metalloproteinase 3 (MMP-3) polymorphisms and the risk of intervertebral disc degeneration susceptibility. The findings were inconsistent. This meta-analysis aimed to systematically assess the association between vitamin D receptor, MMP-3 polymorphisms and the risk of intervertebral disc degeneration susceptibility. A search of various databases was done covering all papers published until December 31th, 2014. Eight, 4, 3 studies were finally included that addressed the risk of intervertebral disc degeneration susceptibility and vitamin D receptor FokI (rs2228570), ApaI (rs7975232), and MMP-3 (rs731236) polymorphisms, respectively. FokI (f vs. F: summary odds ratio [OR], 1.13; 95% confidence interval [CI], 0.76–1.69; ff vs. FF: OR, 1.02; 95% CI, 0.59–1.77; ff vs. Ff/FF: OR, 1.05; 95% CI, 0.70–1.58), ApaI (a vs. A: OR, 0.73; 95% CI, 0.45–1.19; aa vs. AA: OR, 0.53; 95% CI, 0.22–1.25 p=0.14; aa vs. AA/Aa: OR, 0.69; 95% CI, 0.53–0.89) in the vitamin D receptor gene and MMP3 polymorphisms (5A vs. 6A: OR, 1.92; 95% CI, 0.77–4.80; 5A5A vs. 6A6A: OR, 2.17; 95% CI, 0.75–6.24; 5A5A vs. 5A6A/6A6A: OR, 1.58; 95% CI, 0.72–3.44) were not obviously associated with risk of intervertebral disc degeneration susceptibility. FokI, ApaI polymorphisms in the vitamin D receptor gene and MMP-3 polymorphism are not obvious risk factors for intervertebral disc degeneration susceptibility. PMID:27790329

  16. The impact of generalized joint laxity (GJL) on the posterior neck pain, cervical disc herniation, and cervical disc degeneration in the cervical spine.

    PubMed

    Lee, Sun-Mi; Oh, Su Chan; Yeom, Jin S; Shin, Ji-Hoon; Park, Sam-Guk; Shin, Duk-Seop; Ahn, Myun-Whan; Lee, Gun Woo

    2016-12-01

    Generalized joint laxity (GJL) can have a negative impact on lumbar spine pathology, including low back pain, disc degeneration, and disc herniation, but the relationship between GJL and cervical spine conditions remains unknown. To investigate the relationship between GJL and cervical spine conditions, including the prevalence of posterior neck pain (PNP), cervical disc herniation (CDH), and cervical disc degeneration (CDD), in a young, active population. Retrospective 1:2 matched cohort (case-control) study from prospectively collected data PATIENT SAMPLE: Of a total of 1853 individuals reviewed, 73 individuals with GJL (study group, gruop A) and 146 without GJL (control group, Group B) were included in the study according to a 1:2 case-control matched design for age, sex, and body mass index. The primary outcome measure was the prevalence and intensity of PNP at enrollment based on a visual analogue scale score for pain. The secondary outcome measures were (1) clinical outcomes as measured with the neck disability index (NDI) and 12-item short form health survey (SF-12) at enrollment, and (2) radiological outcomes of CDH and CDD at enrollment. We compared baseline data between groups. Descriptive statistical analyses were performed to compare the 2 groups in terms of the outcome measures. The prevalence and intensity of PNP were significantly greater in group A (patients with GJL) than in group B (patients without GJL) (prevalence: p=.02; intensity: p=.001). Clinical outcomes as measured with NDI and SF-12 did not differ significantly between groups. For radiologic outcomes, the prevalence of CDD was significantly greater in group A than in group B (p=.04), whereas the prevalence of CDH did not differ significantly between groups (p=.91). The current study revealed that GJL was closely related to the prevalence and intensity of PNP, suggesting that GJL may be a causative factor for PNP. In addition, GJL may contribute to the occurrence of CDD, but not CDH. Spine

  17. Interrelationship between silicon, aluminum, and elements associated with tissue metabolism and degenerative processes in degenerated human intervertebral disc tissue.

    PubMed

    Zioła-Frankowska, Anetta; Kubaszewski, Łukasz; Dąbrowski, Mikołaj; Frankowski, Marcin

    2017-07-07

    There is a growing body of evidence concerning the significant role of silicon in development and composition of both connective and bone tissue. Bio-essential silicon shows strong chemical and biological affinity to aluminum, which is toxic and biologically inessential element. The presence of silicon was confirmed in a variety of tissues; however, it has never been examined in intervertebral disc tissue, neither in healthy nor in degenerated one. In this paper, for the first time in the literature, we present the content of silicon in the degenerated intervertebral disc tissue. We also compared the results of silicon analysis with aluminum values in degenerated intervertebral disc tissue in humans. We used chemometric methods to find correlations and similarities between silicon, aluminum, and elements associated with tissue metabolism (Mg) and degenerative processes (Zn and Cu). The presence of silicon was confirmed in all 30 samples harvested from 22 patients operated on due to degenerative changes. Its concentration was within the range of 5.37-12.8 μg g(-1) d.w., with the mean concentration of 7.82 μg g(-1) d.w. The analysis showed significant correlation between Si and both Al and Mg and weak or negative correlation with Zn and Cu, where the latter was probably the result of degenerative processes. Although silicon is considered essential in glycosaminoglycan and collagen synthesis in connective tissue, it did not show any correlation nor similarities with elements reflecting changes associated with the degenerative process of the intervertebral disc. Silicon showed significant correlation with aluminum, similar to those observed in other human tissues.

  18. Metabolic Syndrome Components Are Associated with Intervertebral Disc Degeneration: The Wakayama Spine Study

    PubMed Central

    Teraguchi, Masatoshi; Yoshimura, Noriko; Hashizume, Hiroshi; Muraki, Shigeyuki; Yamada, Hiroshi; Oka, Hiroyuki; Minamide, Akihito; Ishimoto, Yuyu; Nagata, Keiji; Kagotani, Ryohei; Tanaka, Sakae; Kawaguchi, Hiroshi; Nakamura, Kozo; Akune, Toru; Yoshida, Munehito

    2016-01-01

    Objective The objective of the present study was to examine the associations between metabolic syndrome (MS) components, such as overweight (OW), hypertension (HT), dyslipidemia (DL), and impaired glucose tolerance (IGT), and intervertebral disc degeneration (DD). Design The present study included 928 participants (308 men, 620 women) of the 1,011 participants in the Wakayama Spine Study. DD on magnetic resonance imaging was classified according to the Pfirrmann system. OW, HT, DL, and IGT were assessed using the criteria of the Examination Committee of Criteria for MS in Japan. Results Multivariable logistic regression analysis revealed that OW was significantly associated with cervical, thoracic, and lumbar DD (cervical: odds ratio [OR], 1.28; 95% confidence interval [CI], 0.92–1.78; thoracic: OR, 1.75; 95% CI, 1.24–2.51; lumbar: OR, 1.87; 95% CI, 1.06–3.48). HT and IGT were significantly associated with thoracic DD (HT: OR, 1.54; 95% CI, 1.09–2.18; IGT: OR, 1.65; 95% CI, 1.12–2.48). Furthermore, subjects with 1 or more MS components had a higher OR for thoracic DD compared with those without MS components (vs. no component; 1 component: OR, 1.58; 95% CI, 1.03–2.42; 2 components: OR, 2.60; 95% CI, 1.62–4.20; ≥3 components: OR, 2.62; 95% CI, 1.42–5.00). Conclusion MS components were significantly associated with thoracic DD. Furthermore, accumulation of MS components significantly increased the OR for thoracic DD. These findings support the need for further studies of the effects of metabolic abnormality on DD. PMID:26840834

  19. T1ρ MRI and Discography Pressure as Novel Biomarkers for Disc Degeneration and Low Back Pain

    PubMed Central

    Borthakur, Arijitt; Maurer, Philip M.; Fenty, Matthew; Wang, Chenyang; Berger, Rachelle; Yoder, Jonathon; Balderston, Richard A.; Elliott, Dawn M.

    2012-01-01

    Study Design Prospective MRI study of LBP patients requiring discography as part of their routine clinical diagnoses and asymptomatic age-matched volunteers. Objective To determine whether T1ρ MRI and discography opening pressure are quantitative biomarkers of disc degeneration in LBP patients and in asymptomatic volunteers. Summary of Background Data Disc degenerative disease (DDD), a common cause of low back pain (LBP), is related to the patient’s prognosis and serves as a target for therapeutic interventions. However, there are few quantitative measures in the clinical setting. Discography opening pressure (OP) and T1ρ MRI are potential biomarkers of DDD related to biochemical composition the intervertebral disc (IVD). Methods The Institutional Review Board approved all experiments and informed consent was provided by each subject. Patients being treated for LBP (n=17, 68 levels, mean age 44±6 years, range 30–53) and control (CTL) subjects (n=11, 44 levels, mean age 43±17, range 22–76) underwent T1ρ and T2 MRI on a Siemens 3T Tim Trio clinical scanner. The LBP patients also received multi-level provocative discography before their MRI. Opening Pressure (OP) was recorded as the pressure when fluid first enters the nucleus of the IVD. Results T1ρ was significantly lower in the painful discs (55.3ms±3.0 ms, mean ± std. error) from control (92.0±4.9 ms, p<0.001) and non-painful discs (83.6±3.2 ms, p<0.001). Mean OP for the painful discs (11.8±1.0 psi, mean ± std. error) was significantly lower than non-painful discs (19.1±0.7 psi, p<0.001). Both T1ρ and OP correlated moderately with Pfirrmann degenerative grade. ROC area under the curve was 0.91 for T1ρ MRI and 0.84 for OP for predicting painful discs. Conclusions T1ρ and OP are quantitative measures of degeneration that are consistent across both control subjects and LBP patients. A significant and strong correlation exists between T1ρ values and in vivo OP measurements obtained by

  20. Transplantation of human mesenchymal stems cells into intervertebral discs in a xenogeneic porcine model.

    PubMed

    Henriksson, Helena B; Svanvik, Teresia; Jonsson, Marianne; Hagman, Margret; Horn, Michael; Lindahl, Anders; Brisby, Helena

    2009-01-15

    Experimental and descriptive study of a xenotransplantation model in minipigs. To study survival and function of human mesenchymal stem cells (hMSCs) after transplantation into injured porcine spinal discs, as a model for cell therapy. Biologic treatment options of the intervertebral disc are suggested for patients with chronic low back pain caused by disc degeneration. Three lumbar discs in each of 9 minipigs were injured by aspiration of the nucleus pulposus (NP), 2 weeks later hMSCs were injected in F12 media suspension (cell/med) or with a hydrogel carrier (Puramatrix) (cell/gel). The animals were sacrificed after 1, 3, or 6 months. Disc appearance was visualized by magnetic resonance imaging. Immunohistochemistry methods were used to detect hMSCs by antihuman nuclear antibody staining, and further performed for Collagen II, Aggrecan, and Collagen I. SOX 9, Aggrecan, Versican, Collagen IA, and Collagen IIA and Collagen IIB human mRNA expression was analyzed by real-time PCR. At magnetic resonance imaging all injured discs demonstrated degenerative signs. Cell/gel discs showed fewer changes compared with cell/med discs and only injured discs at later time points. hMSCs were detected in 9 of 10 of the cell/gel discs and in 8 of 9 of the cell/med discs. Immunostaining for Aggrecan and Collagen type II expression were observed in NP after 3 and 6 months in gel/cell discs and colocalized with the antihuman nuclear antibody. mRNA expression of Collagen IIA, Collagen IIB, Versican, Collagen 1A, Aggrecan, and SOX9 were detected in both cell/med and cell/gel discs at the time points 3 and 6 months by real-time PCR. hMSCs survive in the porcine disc for at least 6 months and express typical chondrocyte markers suggesting differentiation toward disc-like cells. As in autologous animal models the combination with a three-dimensional-hydrogel carrier seems to facilitate differentiation and survival of MSCs in the disc. Xenotransplantation seems to be valuable in evaluating

  1. The relationship between sagittal spinopelvic parameters and the degree of lumbar intervertebral disc degeneration in young adult patients with low-grade spondylolytic spondylolisthesis.

    PubMed

    Oh, Y-M; Eun, J-P

    2013-09-01

    We investigated the relationship between spinopelvic parameters and disc degeneration in young adult patients with spondylolytic spondylolisthesis. A total of 229 men with a mean age of 21 years (18 to 26) with spondylolytic spondylolisthesis were identified. All radiological measurements, including pelvic incidence, sacral slope, pelvic tilt, lumbar lordosis, sacral inclination, lumbosacral angle (LSA), and sacrofemoral distance, were calculated from standing lateral lumbosacral radiographs. The degree of intervertebral disc degeneration was classified using a modified Pfirrmann scale. We analysed the spinopelvic parameters according to disc level, degree of slip and disc degeneration. There were significant positive correlations between the degree of slip and pelvic incidence (p = 0.009), sacral slope (p = 0.003) and lumbar lordosis (p = 0.010). The degree of slip and the LSA were correlated with disc degeneration (p < 0.001 and p = 0.003, respectively). There was also a significant difference between the degree of slip (p < 0.001) and LSA (p = 0.006) according to the segmental level of disc degeneration.

  2. Oxidative damage induces apoptosis and promotes calcification in disc cartilage endplate cell through ROS/MAPK/NF-κB pathway: Implications for disc degeneration.

    PubMed

    Han, Yingchao; Li, Xinhua; Yan, Meijun; Yang, Mingjie; Wang, Shanjin; Pan, Jie; Jun, Lili; Tan, Jun

    2017-03-23

    Cartilage endplate (CEP) cell calcification and apoptosis play a vital role in the intervertebral disc degeneration (IVDD). Oxidative stress is a key factor in inducing programmed cell death and cartilage calcification. However, the cell death and calcification of cartilage endplate cells under oxidative stress have never been described. The present study investigated the apoptosis and calcification in the cartilage endplate cell under oxidative stress induced by H2O2 to understand the underlying mechanism of IVDD. The cartilage endplate cells isolated from human lumbar discs were subjected to different concentrations of H2O2 for various time periods. The cell viability was determined by CCK-8 assay, whereas Western blot, immunofluorescence, and Alcian blue, Alizarin red, and Von Kossa staining evaluated the apoptosis and calcification. The level of mitochondria-specific reactive oxygen species (ROS) was quantified with an oxygen radical-sensitive probe-MitoSOX. The potential signaling pathways were investigated by Western blot after the addition of N-acetyl-l-cysteine (NAC). We found that the oxidative stress induced by H2O2 increased the apoptosis and subsequently the calcification in the cartilage endplate cells through the ROS/p38/ERK/p65 pathway. The apoptosis and the calcification of the cartilage endplate cells induced by H2O2 can be abolished by NAC. These results suggested that regulating the apoptosis and the calcification in the cartilage endplate cells under oxidative stress should be advantageous for the survival of cells and might delay the process of disc degeneration.

  3. Minimum 10-Year Follow-up Study of Anterior Lumbar Interbody Fusion for Degenerative Spondylolisthesis: Progressive Pattern of the Adjacent Disc Degeneration

    PubMed Central

    Yasuda, Taketoshi; Hori, Takeshi; Suzuki, Kayo; Kawaguchi, Yoshiharu

    2012-01-01

    Study Design Retrospective study. Purpose The aims of the current study are to evaluate the minimum 10-year follow-up clinical results of anterior lumbar interbody fusion (ALIF) for degenerative spondylolisthesis. Overview of Literature ALIF has been widely used as a treatment regimen in the management of lumbar spondylolisthesis. Still much controversy exists regarding the factors that affect the postoperative clinical outcomes. Methods The author performed a retrospective review of 20 patients with degenerative spondylolisthesis treated with ALIF (follow-up, 16.4 years). The clinical results were assessed by the Japanese Orthopaedic Association (JOA) score for low back pain, vertebral slip and disc height index on the radiographs. Results The mean preoperative JOA score was 7.1 ± 1.8 points (15-point-method). At 1 year, 5 years, and 10 years or more after surgery, the JOA scores were assessed as 12.4 ± 2.2 points, 12.7 ± 2.6 points, 12.0 ± 2.5 points, respectively (excluding the data of reoperated cases). The adjacent disc degeneration developed in all cases during the long-term follow-up. The progressive pattern of disc degeneration was divided into three types. Initially, disc degeneration occurred due to disc space narrowing. After that, the intervertebral discs showed segmental instability with translation at the upper level. But the lower discs showed osteophyte formation, and occasionally lead to the collapse or spontaneous union. Conclusions The clinical results of the long-term follow-up data after ALIF became worse due to the adjacent disc degeneration. The progressive pattern of disc degeneration was different according to the adjacent levels. PMID:22708014

  4. Spine degeneration in a murine model of chronic human tobacco smokers

    PubMed Central

    Wang, Dong; Nasto, Luigi A; Roughley, Peter; Leme, Adriana S.; Houghton, McGarry; Usas, Arvydas; Sowa, Gwendolyn; Lee, Joon; Niedernhofer, Laura; Shapiro, Steven; Kang, James; Vo, Nam

    2012-01-01

    Objective To investigate the mechanisms by which chronic tobacco smoking promotes intervertebral disc degeneration (IDD) and vertebral degeneration in mice. Methods Three months old C57BL/6 mice were exposed to tobacco smoke by direct inhalation (5 cigarettes/day, 5 days/week for 6 months) to model long-term smoking in humans. Total disc proteoglycan content (DMMB assay), aggrecan proteolysis (immunobloting analysis), and cellular senescence (p16INK4a immunohistochemistry) were analyzed. Proteoglycan and collagen syntheses (35S-sulfate and 3H-proline incorporation, respectively) were measured using disc organotypic culture. Vertebral osteoporosity was measured by micro-computed tomography. Results Disc proteoglycan content of smoke-exposed mice was 63% of unexposed control, while new proteoglycan and collagen syntheses were 59% and 41% of those of untreated mice, respectively. Exposure to tobacco smoke dramatically increased metalloproteinase-mediated proteolysis of disc aggrecan within its interglobular domain (IGD). Cellular senescence was elevated two folds in discs of smoke-exposed mice. Smoke exposure increased vertebral endplate porosity, which closely correlates with IDD in humans. Conclusions These findings further support tobacco smoke as a contributor to spinal degeneration. Furthermore, the data provide a novel mechanistic insight, indicating that smoking-induced IDD is a result of both reduced PG synthesis and increased degradation of a key disc extracellular matrix protein, aggrecan. Cleavage of aggrecan IGD is extremely detrimental as this result in the loss of the entire glycosaminoglycan-attachment region of aggrecan, which is vital for attracting water necessary to counteract compressive forces. Our results suggest identification and inhibition of specific metalloproteinases responsible for smoke-induced aggrecanolysis as a potential therapeutic strategy to treat IDD. PMID:22531458

  5. Photoreceptor Cells Influence Retinal Vascular Degeneration in Mouse Models of Retinal Degeneration and Diabetes

    PubMed Central

    Liu, Haitao; Tang, Jie; Du, Yunpeng; Saadane, Aicha; Tonade, Deoye; Samuels, Ivy; Veenstra, Alex; Palczewski, Krzysztof; Kern, Timothy S.

    2016-01-01

    Purpose Loss of photoreceptor cells is associated with retinal vascular degeneration in retinitis pigmentosa, whereas the presence of photoreceptor cells is implicated in vascular degeneration in diabetic retinopathy. To investigate how both the absence and presence of photoreceptors could damage the retinal vasculature, we compared two mouse models of photoreceptor degeneration (opsin−/− and RhoP23H/P23H ) and control C57Bl/5J mice, each with and without diabetes. Methods Retinal thickness, superoxide, expression of inflammatory proteins, ERG and optokinetic responses, leukocyte cytotoxicity, and capillary degeneration were evaluated at 1 to 10 months of age using published methods. Results Retinal photoreceptor cells degenerated completely in the opsin mutants by 2 to 4 months of age, and visual function subsided correspondingly. Retinal capillary degeneration was substantial while photoreceptors were still present, but slowed after the photoreceptors degenerated. Diabetes did not further exacerbate capillary degeneration in these models of photoreceptor degeneration, but did cause capillary degeneration in wild-type animals. Photoreceptor cells, however, did not degenerate in wild-type diabetic mice, presumably because the stress responses in these cells were less than in the opsin mutants. Retinal superoxide and leukocyte damage to retinal endothelium contributed to the degeneration of retinal capillaries in diabetes, and leukocyte-mediated damage was increased in both opsin mutants during photoreceptor cell degeneration. Conclusions Photoreceptor cells affect the integrity of the retinal microvasculature. Deterioration of retinal capillaries in opsin mutants was appreciable while photoreceptor cells were present and stressed, but was less after photoreceptors degenerated. This finding proves relevant to diabetes, where persistent stress in photoreceptors likewise contributes to capillary degeneration. PMID:27548901

  6. A meta-model analysis of a finite element simulation for defining poroelastic properties of intervertebral discs.

    PubMed

    Nikkhoo, Mohammad; Hsu, Yu-Chun; Haghpanahi, Mohammad; Parnianpour, Mohamad; Wang, Jaw-Lin

    2013-06-01

    Finite element analysis is an effective tool to evaluate the material properties of living tissue. For an interactive optimization procedure, the finite element analysis usually needs many simulations to reach a reasonable solution. The meta-model analysis of finite element simulation can be used to reduce the computation of a structure with complex geometry or a material with composite constitutive equations. The intervertebral disc is a complex, heterogeneous, and hydrated porous structure. A poroelastic finite element model can be used to observe the fluid transferring, pressure deviation, and other properties within the disc. Defining reasonable poroelastic material properties of the anulus fibrosus and nucleus pulposus is critical for the quality of the simulation. We developed a material property updating protocol, which is basically a fitting algorithm consisted of finite element simulations and a quadratic response surface regression. This protocol was used to find the material properties, such as the hydraulic permeability, elastic modulus, and Poisson's ratio, of intact and degenerated porcine discs. The results showed that the in vitro disc experimental deformations were well fitted with limited finite element simulations and a quadratic response surface regression. The comparison of material properties of intact and degenerated discs showed that the hydraulic permeability significantly decreased but Poisson's ratio significantly increased for the degenerated discs. This study shows that the developed protocol is efficient and effective in defining material properties of a complex structure such as the intervertebral disc.

  7. TLIF for symptomatic disc degeneration: a retrospective study of 100 patients.

    PubMed

    Mura, Pier Paolo; Costaglioli, Mauro; Piredda, Maurizio; Caboni, Silvia; Casula, Silvia

    2011-05-01

    The goal of a fusion of the lumbar spine is to obtain a primary solid arthrodesis thus to alleviate pain. Different circumferential fusion techniques have been described such as combined anterior-posterior fusion (APF), instrumented posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF). The TLIF procedure has rapidly gained popularity; because of its posterolateral extracanalar discectomy and fusion, it has been reported as a safe technique, without the potential complications described when using combined APF and PLIF techniques. A retrospective clinical and radiographic study was performed. The database of our Center was interrogated in a retrospective way to extract data from patients that underwent a one or two level lumbar fusion with TLIF approach. All patients had symptomatic disc degeneration of the lumbar spine. One hundred and fourteen levels fused from 2003 to 2008. All patients were operated in the same center. All the patients were operated by the same surgical team. Patients were evaluated preoperatively and postoperatively at 1 and 3 months and 1 and 2 years follow-up. The spine was approached through a classic posterior midline incision and subperiosteal muscular detachment. The side of facetectomy was chosen according to the subject's symptoms of leg pain if present. A posterolateral annulotomy was made and subtotal discectomy was performed and the hyaline cartilage of endplates was removed. Once the surgeon was satisfied with endplate preparation, a banana shaped allograft spacer was inserted through the annulotomy and placed anteriorly. Additional autograft locally harvested from decompression was packed behind the allograft spacer in all cases. Laminae and the remaining contralateral facet joint were decorticated, and packed with bone graft (local autologous and allograft chips in some cases). The posterior fusion was instrumented with pedicle screws and titanium rods. The TLIF procedure had led to shortened

  8. Adjacent segment degeneration following ProDisc-C total disc replacement (TDR) and anterior cervical discectomy and fusion (ACDF): does surgeon bias effect radiographic interpretation?

    PubMed

    Laxer, Eric B; Brigham, Craig D; Darden, Bruce V; Bradley Segebarth, P; Alden Milam, R; Rhyne, Alfred L; Odum, Susan M; Spector, Leo R

    2017-04-01

    Many investigators have reported the financial conflicts of interest (COI), which could result in potential bias in the reporting of outcomes for patients undergoing total disc replacement (TDR) rather than anterior cervical discectomy and fusion (ACDF). This bias may be subconsciously introduced by the investigator in a non-blinded radiographic review. The purpose of this study was to determine if bias was present when a group of spine specialists rated adjacent segment degeneration (ASD) following cervical TDR or ACDF. Potential bias in the assessment of ASD was evaluated through the reviews of cervical radiographs (pre- and 6 years post-operative) from patients participating in the ProDisc-C FDA trial (ProDisc-C IDE #G030059). The index level was blinded on all radiographs during the first review, but unblinded in the second. Five reviewers (a radiologist, two non-TDR surgeons, and two TDR surgeons), two of whom had a COI with the ProDisc-C trial sponsor, assessed ASD on a three point scale: yes, no, or unable to assess. Intra- and inter-rater reliabilities between all raters were assessed by the Kappa statistic. The intra-rater reliability between reviews was substantial, indicating little to no bias in assessing ASD development/progression. The Kappa statistics were 0.580 and 0.644 for the TDR surgeons (p < 0.0001), 0.718 and 0.572 for the non-TDR surgeons (p < 0.0001), and 0.642 for the radiologist (p < 0.0001). Inter-rater reliability for the blinded review ranged from 0.316 to 0.607 (p < 0.0001) and from 0.221 to 0.644 (p < 0.0001) for the unblinded review. The knowledge of the surgical procedure performed did not bias the assessment of ASD.

  9. Single Nucleotide Variants of Candidate Genes in Aggrecan Metabolic Pathway Are Associated with Lumbar Disc Degeneration and Modic Changes

    PubMed Central

    Dissanayake, Poruwalage Harsha; Senarath, Upul; Wijayaratne, Lalith Sirimevan; Karunanayake, Aranjan Lional; Dissanayake, Vajira Harshadeva Weerabaddana

    2017-01-01

    Introduction Lumbar disc degeneration (LDD) is genetically determined and severity of LDD is associated with Modic changes. Aggrecan is a major proteoglycan in the intervertebral disc and end plate. Progressive reduction of aggrecan is a main feature of LDD and Modic changes. Objectives The study investigated the associations of single nucleotide variants (SNVs) of candidate genes in the aggrecan metabolic pathway with the severity of LDD and Modic changes. In-silico functional analysis of significant SNVs was also assessed. Methods A descriptive cross sectional study was carried out on 106 patients with chronic mechanical low back pain. T1, T2 sagittal lumbar MRI scans were used to assess the severity of LDD and Modic changes. 62 SNVs in ten candidate genes (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on Sequenom MassARRAY iPLEX platform. Multiple linear regression analysis was carried out using PLINK 1.9 in accordance with additive genetic model. In-silico functional analysis was carried out using Provean, SIFT, PolyPhen and Mutation Taster. Results Mean age was 52.42±9.42 years. 74 (69.8%) were females. The rs2856836, rs1304037, rs17561 and rs1800587 variants of the IL1A gene were associated with the severity of LDD and Modic changes. The rs41270041 variant of the ADAMTS4 gene and the rs226794 variant of the ADAMTS5 gene were associated with severity of LDD while the rs34884997 variant of the ADAMTS4 gene, the rs55933916 variant of the ADAMTS5 gene and the rs9862 variant of the TIMP3 gene were associated with severity of Modic changes. The rs17561 variant of the IL1A gene was predicted as pathogenic by the PolyPhen prediction tool. Conclusions SNVs of candidate genes in ACAN metabolic pathway are associated with severity of LDD and Modic changes in patients with chronic mechanical low back pain. Predictions of in-silico functional analysis of significant SNVs are inconsistent. PMID:28081267

  10. Calcification in the ovine intervertebral disc: a model of hydroxyapatite deposition disease

    PubMed Central

    Burkhardt, D.; Taylor, T. K. F.; Dillon, C. T.; Read, R.; Cake, M.; Little, C. B.

    2009-01-01

    The study design included a multidisciplinary examination of the mineral phase of ovine intervertebral disc calcifications. The objective of the study was to investigate the mineral phase and its mechanisms of formation/association with degeneration in a naturally occurring animal model of disc calcification. The aetiology of dystrophic disc calcification in adult humans is unknown, but occurs as a well-described clinical disorder with hydroxyapatite as the single mineral phase. Comparable but age-related pathology in the sheep could serve as a model for the human disorder. Lumbar intervertebral discs (n = 134) of adult sheep of age 6 years (n = 4), 8 years (n = 12) and 11 years (n = 2) were evaluated using radiography, morphology, scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray powder diffraction, histology, immunohistology and proteoglycan analysis. Half of the 6-year, 84% of the 8-year and 86% of the 11-year-old discs had calcific deposits. These were not well delineated by plain radiography. They were either: (a) punctate deposits in the outer annulus, (b) diffuse deposits in the transitional zone or inner annulus fibrosus with occasional deposits in the nucleus, or (c) large deposits in the transitional zone extending variably into the nucleus. Their maximal incidence was in the lower lumbar discs (L4/5–L6/7) with no calcification seen in the lumbosacral or lower thoracic discs. All deposits were hydroxyapatite with large crystallite sizes (800–1,300 Å) compared to cortical bone (300–600 Å). No type X-collagen, osteopontin or osteonectin were detected in calcific deposits, although positive staining for bone sialoprotein was evident. Calcified discs had less proteoglycan of smaller hydrodynamic size than non-calcified discs. Disc calcification in ageing sheep is due to hydroxyapatite deposition. The variable, but large, crystal size and lack of protein markers indicate that this does not occur by

  11. Grand Challenges in Protoplanetary Disc Modelling

    NASA Astrophysics Data System (ADS)

    Haworth, Thomas J.; Ilee, John D.; Forgan, Duncan H.; Facchini, Stefano; Price, Daniel J.; Boneberg, Dominika M.; Booth, Richard A.; Clarke, Cathie J.; Gonzalez, Jean-François; Hutchison, Mark A.; Kamp, Inga; Laibe, Guillaume; Lyra, Wladimir; Meru, Farzana; Mohanty, Subhanjoy; Panić, Olja; Rice, Ken; Suzuki, Takeru; Teague, Richard; Walsh, Catherine; Woitke, Peter; Community authors

    2016-10-01

    The Protoplanetary Discussions conference-held in Edinburgh, UK, from 2016 March 7th-11th-included several open sessions led by participants. This paper reports on the discussions collectively concerned with the multi-physics modelling of protoplanetary discs, including the self-consistent calculation of gas and dust dynamics, radiative transfer, and chemistry. After a short introduction to each of these disciplines in isolation, we identify a series of burning questions and grand challenges associated with their continuing development and integration. We then discuss potential pathways towards solving these challenges, grouped by strategical, technical, and collaborative developments. This paper is not intended to be a review, but rather to motivate and direct future research and collaboration across typically distinct fields based on community-driven input, to encourage further progress in our understanding of circumstellar and protoplanetary discs.

  12. Characteristics and potentials of stem cells derived from human degenerated nucleus pulposus: potential for regeneration of the intervertebral disc.

    PubMed

    Li, Xiao-Chuan; Tang, Yong; Wu, Jian-Hong; Yang, Pu-Shan; Wang, De-Li; Ruan, Di-Ke

    2017-06-05

    Eliminating the symptoms during treatment of intervertebral disc degeneration (IVDD) is only a temporary solution that does not cure the underlying cause. A biological method to treat this disorder may be possible by the newly discovered nucleus pulposus derived stem cells (NPDCs). However, the uncertain characteristics and potential of NPDCs calls for a comprehensive study. In the present study, nucleus pulposus samples were obtained from 5 patients with IVDD undergoing discectomy procedure and NPDCs were harvested using fluorescence activated cell sorting (FACS) by the co-expression of GD2(+) and Tie2(+). After in vitro expansion, the properties of NPDCs were compared with those of bone marrow mesenchyme stem cells (BMSCs) from the same subjects. NPDCs performed similar properties in cell colony-forming ability, cell proliferation rate, cell cycle and stem cell gene expression similar to those of BMSCs. In addition, NPDCs could be differentiated into osteoblasts, adipocytes, and chondrocytes, and are found to be superior in chondrogenesis but inferior in adipocyte differentiation. NPDCs derived from the degenerated intervertebral disc still keep the regeneration ability similar to BMSCs. Besides, the superior capacity in chondrogenesis may provide a promising cell candidate for cell-based regenerative medicine and tissue engineering in IVDD.

  13. Gaseous discs at intermediate redshifts from kinematic data modelling

    NASA Astrophysics Data System (ADS)

    Kipper, R.; Tamm, A.; Tenjes, P.; Tempel, E.

    2016-10-01

    Our purpose is to measure thickness of gaseous discs in 0 < z < 1.2 galaxies. As gas dispersions are sensitive to scale height of gaseous discs, we model the kinematics of galaxies using Jeans equations. The resulting thicknesses of gaseous discs at higher redshifts are more thicker (and arbitrary) while nearby ones are thinner. We also found that clumpiness of galaxy is a possible indicator of the gas disc thickness.

  14. Optic Disc Localization Using Directional Models.

    PubMed

    Wu, Xiangqian; Dai, Baisheng; Bu, Wei

    2016-07-13

    Reliable localization of the optic disc (OD) is important for retinal image analysis and ophthalmic pathology screening. This paper presents a novel method to automatically localize ODs in retinal fundus images based on directional models. According to the characteristics of retina vessel networks, such as their origin at the OD and parabolic shape of the main vessels, a global directional model, named the relaxed bi-parabola directional model (R-BPDM), is firstly built. In this model the main vessels are modeled by using two parabolas with a shared vertex and different parameters. Then a local directional model, named the disc directional model (DDM), is built to characterize the local vessel convergence in the OD as well as the shape and the brightness of the OD. Finally, the global and the local directional models are integrated to form a hybrid directional model, which can exploit the advantages of the global and local models for highly accurate OD localization. The proposed method is evaluated on nine publicly available databases, and achieves an accuracy of 100% for each database, which demonstrates the effectiveness of the proposed OD localization method.

  15. Translation of an engineered nanofibrous disc-like angle-ply structure for intervertebral disc replacement in a small animal model.

    PubMed

    Martin, John T; Milby, Andrew H; Chiaro, Joseph A; Kim, Dong Hwa; Hebela, Nader M; Smith, Lachlan J; Elliott, Dawn M; Mauck, Robert L

    2014-06-01

    Intervertebral disc degeneration has been implicated in the etiology of low back pain; however, the current surgical strategies for treating symptomatic disc disease are limited. A variety of materials have been developed to replace disc components, including the nucleus pulposus (NP), the annulus fibrosus (AF) and their combination into disc-like engineered constructs. We have previously shown that layers of electrospun poly(ε-caprolactone) scaffold, mimicking the hierarchical organization of the native AF, can achieve functional parity with native tissue. Likewise, we have combined these structures with cell-seeded hydrogels (as an NP replacement) to form disc-like angle-ply structures (DAPS). The objective of this study was to develop a model for the evaluation of DAPS in vivo. Through a series of studies, we developed a surgical approach to replace the rat caudal disc with an acellular DAPS and then stabilized the motion segment via external fixation. We then optimized cell infiltration into DAPS by including sacrificial poly(ethylene oxide) layers interspersed throughout the angle-ply structure. Our findings illustrate that DAPS are stable in the caudal spine, are infiltrated by cells from the peri-implant space and that infiltration is expedited by providing additional routes for cell migration. These findings establish a new in vivo platform in which to evaluate and optimize the design of functional disc replacements.

  16. Analysis of the Relationship between Ligamentum Flavum Thickening and Lumbar Segmental Instability, Disc Degeneration, and Facet Joint Osteoarthritis in Lumbar Spinal Stenosis

    PubMed Central

    Yoshiiwa, Toyomi; Notani, Naoki; Ishihara, Toshinobu; Kawano, Masanori; Tsumura, Hiroshi

    2016-01-01

    Study Design Cross-sectional study. Purpose To investigate the relationship between ligamentum flavum (LF) thickening and lumbar segmental instability and disc degeneration and facet joint osteoarthritis. Overview of Literature Posterior spinal structures, including LF thickness, play a major role in lumbar spinal canal stenosis pathogenesis. The cause of LF thickening is multifactorial and includes activity level, age, and mechanical stress. LF thickening pathogenesis is unknown. Methods We examined 419 patients who underwent computed tomography (CT) myelography and magnetic resonance imaging after complaints of clinical symptoms. To investigate LF hypertrophy, 57 patients whose lumbar vertebra had normal disc heights at L4–5 were selected to exclude LF buckling as a hypertrophy component. LF thickness, disc space widening angulation in flexion, segmental angulation, presence of a vacuum phenomenon, and lumbar lordosis at T12–S1 were investigated. Disc and facet degeneration were also evaluated. Facet joint orientation was measured via an axial CT scan. Results The mean LF thickness in all patients was 4.4±1.0 mm at L4–5. There was a significant correlation between LF thickness and disc degeneration; LF thickness significantly increased with severe disc degeneration and facet joint osteoarthritis. There was a tendency toward increased LF thickness in more sagittalized facet joints than in coronalized facet joints. Logistic regression analysis showed that LF thickening was influenced by segmental angulation and facet joint osteoarthritis. Patient age was associated with LF thickening. Conclusions LF hypertrophy development was associated with segmental instability and severe disc degeneration, severe facet joint osteoarthritis, and a sagittalized facet joint orientation. PMID:27994791

  17. Matrix stiffness promotes cartilage endplate chondrocyte calcification in disc degeneration via miR-20a targeting ANKH expression

    PubMed Central

    Liu, Ming-Han; Sun, Chao; Yao, Yuan; Fan, Xin; Liu, Huan; Cui, You-Hong; Bian, Xiu-Wu; Huang, Bo; Zhou, Yue

    2016-01-01

    The mechanical environment is crucial for intervertebral disc degeneration (IDD). However, the mechanisms underlying the regulation of cartilage endplate (CEP) calcification by altered matrix stiffness remain unclear. In this study, we found that matrix stiffness of CEP was positively correlated with the degree of IDD, and stiff matrix, which mimicked the severe degeneration of CEP, promoted inorganic phosphate-induced calcification in CEP chondrocytes. Co-expression analysis of the miRNA and mRNA profiles showed that increasing stiffness resulted in up-regulation of miR-20a and down-regulation of decreased ankylosis protein homolog (ANKH) during inorganic phosphate-induced calcification in CEP chondrocytes. Through a dual luciferase reporter assay, we confirmed that miR-20a directly targets 3′-untranslated regions of ANKH. The inhibition of miR-20a attenuated the calcium deposition and calcification-related gene expression, whereas the overexpression of miR-20a enhanced calcification in CEP chondrocytes on stiff matrix. The rescue of ANKH expression restored the decreased pyrophosphate efflux and inhibited calcification. In clinical samples, the levels of ANKH expression were inversely associated with the degeneration degree of CEP. Thus, our findings demonstrate that the miR-20a/ANKH axis mediates the stiff matrix- promoted CEP calcification, suggesting that miR-20a and ANKH are potential targets in restraining the progression of IDD. PMID:27142968

  18. Joint analysis of IVD herniation and degeneration by rat caudal needle puncture model.

    PubMed

    Cunha, Carla; Lamas, Sofia; Gonçalves, Raquel M; Barbosa, Mário A

    2017-02-01

    Intervertebral disc (IVD) degeneration is responsible for various spine pathologies and present clinical treatments are insufficient. Concurrently, the mechanisms behind IVD degeneration are still not completely understood, so as to allow development of efficient tissue engineering approaches. A model of rat IVD degeneration directly coupled to herniation is here proposed in a pilot study. Disc injury is induced by needle puncture, using two different needles gauges: a low caliber 25-G needle and a high caliber 21-G needle. Histological, biochemical, and radiographic degeneration was evaluated at 2 and 6 weeks post-injury. We show that the larger caliber needle results in a more extended histological and radiographic degeneration within the IVD, compared to the smaller one. TUNEL quantification indicates also increased cell death in the 21-G group. Analyses of collagen type I (Picrosirius red staining), collagen type II (immunofluorescence), and GAG content (Blyscan assay) indicate that degeneration features spontaneously recover from 2 to 6 weeks, for both needle types. Moreover, we show the occurrence of hernia proportional to the needle gauge. The number of CD68+ macrophages present, as well as cell apoptosis within the herniated tissue are both proportional to hernia volume. Moreover, hernias formed after lesion tend to spontaneously diminish in volume after 6 weeks. Finally, MMP3 is increased in the hernia in the 21-G group at 2 weeks. This model, by uniquely combining IVD degeneration and IVD herniation in the same animal, may help to understand mechanisms behind IVD pathophysiology, such as hernia formation and spontaneous regression. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:258-268, 2017. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  19. Lumbar intervertebral disc degeneration associated with axial and radiating low back pain in ageing SPARC-null mice.

    PubMed

    Millecamps, Magali; Tajerian, Maral; Naso, Lina; Sage, E Helene; Stone, Laura S

    2012-06-01

    Chronic low back pain (LBP) is a complex, multifactorial disorder with unclear underlying mechanisms. In humans and rodents, decreased expression of secreted protein acidic rich in cysteine (SPARC) is associated with intervertebral disc (IVD) degeneration and signs of LBP. The current study investigates the hypothesis that IVD degeneration is a risk factor for chronic LBP. SPARC-null and age-matched control mice ranging from 6 to 78 weeks of age were evaluated in this study. X-ray and histologic analysis revealed reduced IVD height, increased wedging, and signs of degeneration (bulging and herniation). Cutaneous sensitivity to cold, heat, and mechanical stimuli were used as measures of referred (low back and tail) and radiating pain (hind paw). Region specificity was assessed by measuring icilin- and capsaicin-evoked behaviour after subcutaneous injection into the hind paw or upper lip. Axial discomfort was measured by the tail suspension and grip force assays. Motor impairment was determined by the accelerating rotarod. Physical function was evaluated by voluntary activity after axial strain or during ambulation with forced lateral flexion. SPARC-null mice developed (1) region-specific, age-dependent hypersensitivity to cold, icilin, and capsaicin (hind paw only), (2) axial discomfort, (3) motor impairment, and (4) reduced physical function. Morphine (6 mg/kg, i.p.) reduced cutaneous sensitivity and alleviated axial discomfort in SPARC-null mice. Ageing SPARC-null mice mirror many aspects of the complex and challenging nature of LBP in humans and incorporate both anatomic and functional components of the disease. The current study supports the hypothesis that IVD degeneration is a risk factor for chronic LBP.

  20. Pineal gland calcification, lumbar intervertebral disc degeneration and abdominal aorta calcifying atherosclerosis correlate in low back pain subjects: A cross-sectional observational CT study.

    PubMed

    Turgut, Ahmet Tuncay; Sönmez, Iclal; Cakıt, Burcu Duyur; Koşar, Pınar; Koşar, Uğur

    2008-06-01

    The goal of this cross-sectional observational study was to assess the possible impact of pineal gland calcification upon the intervertebral disc degeneration and abdominal aorta atherosclerosis in subjects with low back pain, and to investigate the course of these processes with aging. The study was carried out on 81 (66 women and 15 men) subjects: younger than 45 years (group X, n=22), 45-65 years of age (group Y, n=45), and older than 65 years (group Z, n=14). In addition to clinical data, computed tomography (CT) scan of the brain as well as X-ray and CT examination of the lumbar spine were recorded in this study. The degree of disc degeneration and calcification rates of aortic wall and pineal gland were independently determined by two radiologists. Both ratio of calcified pineal gland and density of pineal calcification increased progressively with aging. Also, both the degree of aortic wall calcification and disc degeneration score increased with advancing age. On CT scan, a positive correlation between degree of aortic wall calcification and disc degeneration score was found (r=0.306, p<0.01). Importantly, there was a positive association between calcification of the pineal gland and degenerative disc disease in X-ray or CT study (r=0.378 and r=0.295, p<0.005 and p<0.01, respectively), as well as between abdominal aorta atherosclerosis and pineal calcification (r=0.634, p<0.001). Our findings suggest that there is a significant interaction between pineal gland calcification and lumbar intervertebral disc degeneration and also abdominal aorta atherosclerosis. However, further studies with a larger subject cohorts are needed.

  1. Effect of Lumbar Disc Degeneration and Low-Back Pain on the Lumbar Lordosis in Supine and Standing: A Cross-Sectional MRI Study.

    PubMed

    Hansen, Bjarke B; Bendix, Tom; Grindsted, Jacob; Bliddal, Henning; Christensen, Robin; Hansen, Philip; Riis, Robert G C; Boesen, Mikael

    2015-11-01

    Cross-sectional study. To examine the influence of low-back pain (LBP) and lumbar disc degeneration (LDD) on the lumbar lordosis in weight-bearing positional magnetic resonance imaging (pMRI). The lumbar lordosis increases with a change of position from supine to standing and is known as an essential contributor to dynamic changes. However, the lordosis may be affected by disc degeneration and pain. Patients with LBP >40 on a 0 to 100 mm Visual Analog Scale (VAS) both during activity and rest and a sex and age-decade matching control group without LBP were scanned in the supine and standing position in a 0.25-T open MRI unit. LDD was graded using Pfirrmann's grading-scale. Subsequently, the L2-to-S1 lumbar lordosis angle (LA) was measured. Thirty-eight patients with an average VAS of 58 (±13.8) mm during rest and 75 (±5.0) mm during activities, and 38 healthy controls were included. MRI findings were common in both groups, whereas, the summation of the Pfirrmann's grades (LDD-score) was significantly higher in the patients [(MD 1.44; 95% confidence intervals (CI) 0.80 to 2.10; P < 0.001]. The patients were less lordotic than the controls in both the supine (MD -6.4°; 95% CI -11.4 to -1.3), and standing position (MD -5.6°; 95% CI -10.7 to -0.7); however, the changes between the positions (ΔLA) were the same (MD 0.8°; 95% CI -1.8 to 3.3). Using generalized linear model the LDD-score was associated with age (P < 0.001) for both groups. The LDD-score and ΔLA were negatively associated in the control group (P < 0.001), also after adjustments for gender and age (β-coefficient: -2.66; 95% CI -4.3 to -1.0; P = 0.002). Patients may be less lordotic in both the supine and standing position, whereas, change in the lordosis between the positions may be independent of pain. Decreasing lordosis change seems to be associated with age-related increasing disc degeneration in healthy individuals. 2.

  2. Metallurgical modelling of superalloy disc isothermal forgings

    NASA Astrophysics Data System (ADS)

    Evans, R. W.

    1988-08-01

    The metallurgical structure of superalloy aeroengine disc forgings is a complex function of the forging operation parameters and the post forging heat treatment. It is often desirable to obtain certain specific structures in parts of the disc which are, for instance, resistant to crack propagation and this has traditionally been accomplished by means of a series of production trials. This expensive and time consuming procedure can be considerably shortened if the development of microstructure during the forging can be accurately modelled by a suitable computer code. Described here is such a model and its use in the design of isothermal forged components. The model discribed is a fully thermally coupled viscoplasticity finite element algorithm. It treats nodal velocities as the basic unknowns and both the mesh geometry and the various metallurgical structural terms are updated by a single step Euler scheme. Facilities are available for ensuring that surface nodes follow die shapes after impingement, that flow is incompressible and that suitable surface friction forces are applied. Throughout the whole forging process (which may involve the re-meshing of severely distorted elements), the metallurgical history of elements is retained so that the effects of subsequent heat treatments can be assessed.

  3. Atomic Absorption Spectrometry Analysis of Trace Elements in Degenerated Intervertebral Disc Tissue

    PubMed Central

    Kubaszewski, Łukasz; Zioła-Frankowska, Anetta; Frankowski, Marcin; Nowakowski, Andrzej; Czabak-Garbacz, Róża; Kaczmarczyk, Jacek; Gasik, Robert

    2014-01-01

    Background Few studies have investigated trace elements (TE) in human intervertebral disc (IVD) tissue. Trace element presence can have diverse meanings: essential TE show the metabolic modalities of the tissue, while environmentally-related TE indicate pollution and tissue-specific absorption and accumulation. IVD is a highly specific compartment with impaired communication with adjacent bone. Analysis of TE in IVD provides new insights regarding tissue metabolism and IVD communication with other tissues. Material/Methods Thirty intervertebral discs were acquired from 22 patients during surgical treatment for degenerative disease. Atomic absorption spectrometry was used to evaluate the concentrations of Al, Cd, Pb, Cu, Ni, Mo, Mg, and Zn. Results Al, Pb, Cu, Mg, and Zn were detected in all samples. Pb was significantly positively correlated with age, and Ni concentration was weakly correlated with population count in the patient’s place of residence. Only Cu was observed in higher concentrations in IVD compared to in other tissues. Significant positive correlations were observed between the following pairs: Mg/Zn, Mg/Al, Mg/Pb, Zn/Al, Zn/Pb, and Al/Pb. Negative correlations were observed between Mg/Cd, Zn/Cd, Mg/Mo, and Mo/Pb. Conclusions This study is one of few to profile the elements in intervertebral discs in patients with degenerative changes. We report significant differences between trace element concentrations in intervertebral discs compared to in other tissues. Knowledge of the TE accumulation pattern is vital for better understanding intervertebral disc nutrition and metabolism. PMID:25366266

  4. Association of matrilin‐3 polymorphisms with spinal disc degeneration and osteoarthritis of the first carpometacarpal joint of the hand

    PubMed Central

    Min, J L; Meulenbelt, I; Riyazi, N; Kloppenburg, M; Houwing‐Duistermaat, J J; Seymour, A B; van Duijn, C M; Slagboom, P E

    2006-01-01

    Background Seven polymorphisms in the matrilin‐3(MATN3) gene were previously tested for genetic association with hand osteoarthritis in an Icelandic cohort. One of the variants, involving a conserved amino acid substitution (T303M; SNP5), was related to idiopathic hand osteoarthritis. Objectives To investigate SNP5 and two other promising polymorphisms (rs2242190; SNP3, rs8176070; SNP6) for association with radiographic and symptomatic hand osteoarthritis phenotypes, as well as other heritable phenotypes. Methods Polymorphisms were examined in two distinct cohorts of subjects: a population based sample from the Rotterdam study (n = 809), and affected siblings from the genetics, osteoarthrosis and progression (GARP) study (n = 382). Results The originally described association of T303M with the hand osteoarthritis phenotype was not observed in the populations studied. In the Rotterdam sample, however, carrying the T allele of T303M conferred an odds ratio of 2.9 (95% confidence interval (CI), 1.2 to 7.3; p = 0.02) for spinal disc degeneration. In the GARP study, carriers of the A allele of SNP6 had an odds ratio of 2.0 (95% CI, 1.3 to 3.1, p = 0.004) for osteoarthritis of the first carpometacarpal joint (CMC1) as compared with the Rotterdam sample as a control group. Subsequent haplotype analysis showed that a common haplotype, containing the risk allele of SNP6, conferred a significant risk in sibling pairs with CMC1 osteoarthritis (odds ratio = 1.7 (95% CI, 1.1 to 2.7, p = 0.02)). Conclusions These associations suggest that the MATN3 region also determines susceptibility to spinal disc degeneration and CMC1 osteoarthritis. PMID:16396979

  5. Heme oxygenase-1 attenuates IL-1β induced alteration of anabolic and catabolic activities in intervertebral disc degeneration

    PubMed Central

    Hu, Bo; Shi, Changgui; Xu, Chen; Cao, Peng; Tian, Ye; Zhang, Ying; Deng, Lianfu; Chen, Huajiang; Yuan, Wen

    2016-01-01

    Intervertebral disc degeneration (IDD) is characterized by disordered extracellular matrix (ECM) metabolism, implicating subdued anabolism and enhanced catabolic activities in the nucleus pulposus (NP) of discs. Pro-inflammatory cytokines such as interleukin-1β (IL-1β) are considered to be potent mediators of ECM breakdown. Hemeoxygenase-1 (HO-1) has been reported to participate in cellular anti-inflammatory processes. The purpose of this study was to investigate HO-1 modulation of ECM metabolism in human NP cells under IL-1β stimulation. Our results revealed that expression of HO-1 decreased considerably during IDD progression. Induction of HO-1 by cobalt protoporphyrin IX attenuated the inhibition of sulfate glycosaminoglycan and collagen type II (COL-II) synthesis and ameliorated the reduced expressions of aggrecan, COL-II, SOX-6 and SOX-9 mediated by IL-1β. Induction of HO-1 also reversed the effect of IL-1β on expression of the catabolic markers matrix metalloproteinases-1, 3, 9 and 13. This was combined with inhibition of the activation of mitogen-activated protein kinase signaling. These findings suggest that HO-1 might play a pivotal role in IDD, and that manipulating HO-1 expression might mitigate the impairment of ECM metabolism in NP, thus potentially offering a novel therapeutic approach to the treatment of IDD. PMID:26877238

  6. Does elite swimming accelerate lumbar intervertebral disc degeneration and increase low back pain? A cross-sectional comparison.

    PubMed

    Folkvardsen, Steffen; Magnussen, Erland; Karppinen, Jaro; Auvinen, Juha; Larsen, Rasmus Hertzum; Wong, Christian; Bendix, Tom

    2016-09-01

    The aim was to elucidate elite swimming's possible influence on lumbar disc degeneration (DD) and low back pain (LBP). Lumbar spine MRI was performed on a group of elite swimmers and compared to a matched Finnish population-based no-sport group. One hundred elite swimmers and 96 no-sport adults, mean age 18.7/20.8, respectively, participated. Overall, the two groups had similar prevalence of DD. Swimmers had more DD in the upper lumbar spine but tended to have less DD at the lowest level. Prevalence of bulges and disc herniations were similar, but swimmers had significantly more bulges at L4-5. The swimmers reported less LBP, although not significantly (N.S.). If degenerative findings were present, the association between them and LBP was stronger in the no-sport group. Elite swimmers and controls had similar prevalence of DD and LBP, although the pattern of DD differed between the groups. In case of DD, swimmers reported less LBP, although N.S.

  7. A computational model of motor neuron degeneration.

    PubMed

    Le Masson, Gwendal; Przedborski, Serge; Abbott, L F

    2014-08-20

    To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. A COMPUTATIONAL MODEL OF MOTOR NEURON DEGENERATION

    PubMed Central

    Le Masson, Gwendal; Przedborski, Serge; Abbott, L.F.

    2014-01-01

    SUMMARY To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. PMID:25088365

  9. Three-dimensional morphological and signal intensity features for detection of intervertebral disc degeneration from magnetic resonance images

    PubMed Central

    Neubert, A; Fripp, J; Engstrom, C; Walker, D; Weber, M-A; Schwarz, R; Crozier, S

    2013-01-01

    Background and objectives Advances in MRI hardware and sequences are continually increasing the amount and complexity of data such as those generated in high-resolution three-dimensional (3D) scanning of the spine. Efficient informatics tools offer considerable opportunities for research and clinically based analyses of magnetic resonance studies. In this work, we present and validate a suite of informatics tools for automated detection of degenerative changes in lumbar intervertebral discs (IVD) from both 3D isotropic and routine two-dimensional (2D) clinical T2-weighted MRI. Materials and methods An automated segmentation approach was used to extract morphological (traditional 2D radiological measures and novel 3D shape descriptors) and signal appearance (extracted from signal intensity histograms) features. The features were validated against manual reference, compared between 2D and 3D MRI scans and used for quantification and classification of IVD degeneration across magnetic resonance datasets containing IVD with early and advanced stages of degeneration. Results and conclusions Combination of the novel 3D-based shape and signal intensity features on 3D (area under receiver operating curve (AUC) 0.984) and 2D (AUC 0.988) magnetic resonance data deliver a significant improvement in automated classification of IVD degeneration, compared to the combination of previously used 2D radiological measurement and signal intensity features (AUC 0.976 and 0.983, respectively). Further work is required regarding the usefulness of 2D and 3D shape data in relation to clinical scores of lower back pain. The results reveal the potential of the proposed informatics system for computer-aided IVD diagnosis from MRI in large-scale research studies and as a possible adjunct for clinical diagnosis. PMID:23813538

  10. Development of a Large Animal Long-Term Intervertebral Disc Organ Culture Model That Includes the Bony Vertebrae for Ex Vivo Studies.

    PubMed

    Grant, Michael; Epure, Laura M; Salem, Omar; AlGarni, Nizar; Ciobanu, Ovidiu; Alaqeel, Motaz; Antoniou, John; Mwale, Fackson

    2016-07-01

    Intervertebral disc (IVD) degeneration is a common cause of low back pain. Testing potential therapeutics in the regeneration of the disc requires the use of model systems. Although several animal models have been developed to investigate IVD degeneration, they are technically challenging to prepare, expensive, present with limitations when performing biomechanical studies on the disc, and are impractical in large-scale screening of novel anabolic and scaffolding agents. An IVD organ culture system offers an inexpensive alternative. In the current paradigm, the bony endplates are removed to allow for nutrient diffusion and maintenance of disc cell viability. Although this is an excellent system for testing biologics, it results in concave cartilage endplates and, as such, requires special platens for loading purposes in a bioreactor as flat ones can overload the annular disc region leading to improper loading. Furthermore, the absence of bone makes it unsuitable for applying complex cyclic loading, a topic of interest in the study of chronic progressive degeneration, as multiaxial loading is more representative of daily forces encountered by the IVD. We have developed and validated a novel long-term IVD organ culture model that retains vertebral bone and is easy to prepare. Our model is ideal for testing potential drugs and alternate-based therapies, in addition to investigating the long-term effects of loading paradigms on disc degeneration and repair.

  11. Animal models of age related macular degeneration.

    PubMed

    Pennesi, Mark E; Neuringer, Martha; Courtney, Robert J

    2012-08-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations.

  12. Animal models of age related macular degeneration

    PubMed Central

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  13. Novel Human Intervertebral Disc Strain Template to Quantify Regional Three-Dimensional Strains in a Population and Compare to Internal Strains Predicted by a Finite Element Model

    PubMed Central

    Showalter, Brent L.; DeLucca, John F.; Peloquin, John M.; Cortes, Daniel H.; Yoder, Jonathon H.; Jacobs, Nathan T.; Wright, Alexander C.; Gee, James C.; Vresilovic, Edward J.; Elliott, Dawn M.

    2017-01-01

    Tissue strain is an important indicator of mechanical function, but is difficult to noninvasively measure in the intervertebral disc. The objective of this study was to generate a disc strain template, a 3D average of disc strain, of a group of human L4–L5 discs loaded in axial compression. To do so, magnetic resonance images of uncompressed discs were used to create an average disc shape. Next, the strain tensors were calculated pixel-wise by using a previously developed registration algorithm. Individual disc strain tensor components were then transformed to the template space and averaged to create the disc strain template. The strain template reduced individual variability while highlighting group trends. For example, higher axial and circumferential strains were present in the lateral and posterolateral regions of the disc, which may lead to annular tears. This quantification of group-level trends in local 3D strain is a significant step forward in the study of disc biomechanics. These trends were compared to a finite element model that had been previously validated against the disc-level mechanical response. Depending on the strain component, 81–99% of the regions within the finite element model had calculated strains within one standard deviation of the template strain results. The template creation technique provides a new measurement technique useful for a wide range of studies, including more complex loading conditions, the effect of disc pathologies and degeneration, damage mechanisms, and design and evaluation of treatments. PMID:26694516

  14. Interleukin-1 receptor antagonist delivered directly and by gene therapy inhibits matrix degradation in the intact degenerate human intervertebral disc: an in situ zymographic and gene therapy study

    PubMed Central

    Le Maitre, Christine L; Hoyland, Judith A; Freemont, Anthony J

    2007-01-01

    Data implicate IL-1 in the altered matrix biology that characterizes human intervertebral disc (IVD) degeneration. In the current study we investigated the enzymic mechanism by which IL-1 induces matrix degradation in degeneration of the human IVD, and whether the IL-1 inhibitor IL-1 receptor antagonist (IL-1Ra) will inhibit degradation. A combination of in situ zymography (ISZ) and immunohistochemistry was used to examine the effects of IL-1 and IL-1Ra on matrix degradation and metal-dependent protease (MDP) expression in explants of non-degenerate and degenerate human IVDs. ISZ employed three substrates (gelatin, collagen, casein) and different challenges (IL-1β, IL-1Ra and enzyme inhibitors). Immunohistochemistry was undertaken for MDPs. In addition, IL-1Ra was introduced into degenerate IVD explants using genetically engineered constructs. The novel findings from this study are: IL-1Ra delivered directly onto explants of degenerate IVDs eliminates matrix degradation as assessed by multi-substrate ISZ; there is a direct relationship between matrix degradation assessed by ISZ and MDP expression defined by immunohistochemistry; single injections of IVD cells engineered to over-express IL-1Ra significantly inhibit MDP expression for two weeks. Our findings show that IL-1 is a key cytokine driving matrix degradation in the degenerate IVD. Furthermore, IL-1Ra delivered directly or by gene therapy inhibits IVD matrix degradation. IL-1Ra could be used therapeutically to inhibit degeneration of the IVD. PMID:17760968

  15. Bone architecture and disc degeneration in the lumbar spine of mice lacking GDF-8 (myostatin).

    PubMed

    Hamrick, Mark W; Pennington, Catherine; Byron, Craig D

    2003-11-01

    GDF-8, also known as myostatin, is a member of the transforming growth factor-beta superfamily of secreted growth and differentiation factors that is expressed in vertebrate skeletal muscle. Myostatin functions as a negative regulator of skeletal muscle growth and myostatin null mice show a doubling of muscle mass compared to normal mice. We describe here morphology of the lumbar spine in myostatin knockout (Mstn(-/-)) mice using histological and densitometric techniques. The Mstn(-/-) mice examined in this study weigh approximately 10% more than controls (p<0.001) but the iliopsoas muscle is over 50% larger in the knockout mice than in wild-type mice (p<0.001). Peripheral quantitative computed tomography (pQCT) data from the fifth lumbar vertebra show that mice lacking myostatin have approximately 50% greater trabecular bone mineral density (p=0.001) and significantly greater cortical bone mineral content than normal mice. Toluidine blue staining of the intervertebral disc between L4-L5 reveals loss of proteoglycan staining in the hyaline end plates and inner annulus fibrosus of the knockout mice. Loss of cartilage staining in the caudal end plate of L4 is due to ossification of the end plate in the myostatin-deficient animals. Results from this study suggest that increased muscle mass in mice lacking myostatin is associated with increased bone mass as well as degenerative changes in the intervertebral disc.

  16. Narrowing of lumbar spinal canal predicts chronic low back pain more accurately than intervertebral disc degeneration: a magnetic resonance imaging study in young Finnish male conscripts.

    PubMed

    Visuri, Tuomo; Ulaska, Jaana; Eskelin, Marja; Pulkkinen, Pekka

    2005-11-01

    The objective of this magnetic resonance imaging study was to evaluate the role of degenerative changes, developmental spinal stenosis, and compression of spinal nerve roots in chronic low back (CLBP) and radicular pain in Finnish conscripts. The degree of degeneration, protrusion, and herniation of the intervertebral discs and stenosis of the nerve root canals was evaluated, and the midsagittal diameter and cross-sectional area of the lumbar vertebrae canal were measured in 108 conscripts with CLBP and 90 asymptomatic controls. The midsagittal diameters at L1-L4 levels were significantly smaller in the patients with CLBP than in the controls. Moreover, degeneration of the L4/5 disc and protrusion or herniation of the L5/S1 disc and stenosis of the nerve root canals at level L5/S1 were more frequent among the CLBP patients. Multifactorial analysis of the magnetic resonance imaging findings provided a total explanatory rate of only 33%. Narrowing of the vertebral canal in the anteroposterior direction was more likely to produce CLBP and radiating pain than intervertebral disc degeneration or narrowing of the intervertebral nerve root canals.

  17. Is there a role for endothelial dysfunction in the pathogenesis of lumbar disc degeneration? A hypothesis that needs to be tested.

    PubMed

    Papalia, Rocco; Albo, Erika; Vadalà, Gianluca; D'Adamio, Stefano; Lanotte, Angela; Di Martino, Alberto; Denaro, Vincenzo

    2015-03-01

    Low back pain is a painful condition affecting most people at least once in their life. It can be the expression of lumbar disc degeneration, a condition whose progression is influenced by environmental, individual and genetic factors. The pathogenesis of this condition implies the reduction of sustenance for the tissues within the intervertebral disc (ID) due to a decreased blood flow in the local microcirculation. In fact, it is known that the ID is an avascular structure that receives nutritive molecules and exchanges waste products through a process of osmotic diffusion from the capillaries located at the ID-vertebral body interface. The maintenance of a correct oxygen supply is essential for the health of disc cells also because ID is subjected to continuous compression stress due to its bearing function between vertebral bodies. This vital condition is guaranteed by proper dilation of blood vessels in response to mechanical stress, thanks to a finely balanced homeostasis between vasodilatory factors, such as nitric oxide, and vasoconstrictive substances produced by the endothelium. Endothelial dysfunction may disrupt this delicate equilibrium, causing a reduced oxygen supply eventually resulting in ID degeneration. Our hypothesis is that endothelial dysfunction, a systemic condition of reduced vessel dilation in response to mechanical stress, should be considered as an important pathological factor implicated intervertebral disc degeneration. This relationship may pave the way for a change in therapeutic approach to low back pain, especially in the early stages. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Physiological Loading Can Restore the Proteoglycan Content in a Model of Early IVD Degeneration

    PubMed Central

    Gawri, Rahul; Moir, Janet; Ouellet, Jean; Beckman, Lorne; Steffen, Thomas; Roughley, Peter; Haglund, Lisbet

    2014-01-01

    A hallmark of early IVD degeneration is a decrease in proteoglycan content. Progression will eventually lead to matrix degradation, a decrease in weight bearing capacity and loss of disc height. In the final stages of IVD degradation, fissures appear in the annular ring allowing extrusion of the NP. It is crucial to understand the interplay between mechanobiology, disc composition and metabolism to be able to provide exercise recommendations to patients with early signs of disc degeneration. This study evaluates the effect of physiological loading compared to no loading on matrix homeostasis in bovine discs with induced degeneration. Bovine discs with trypsin-induced degeneration were cultured for 14 days in a bioreactor under dynamic loading with maintained metabolic activity. Chondroadherin abundance and structure was used to confirm that a functional matrix was preserved in the chosen loading environment. No change was observed in chondroadherin integrity and a non-significant increase in abundance was detected in trypsin-treated loaded discs compared to unloaded discs. The proteoglycan concentration in loaded trypsin-treated discs was significantly higher than in unloaded disc and the newly synthesised proteoglycans were of the same size range as those found in control samples. The proteoglycan showed an even distribution throughout the NP region, similar to that of control discs. Significantly more newly synthesised type II collagen was detected in trypsin-treated loaded discs compared to unloaded discs, demonstrating that physiological load not only stimulates aggrecan production, but also that of type II collagen. Taken together, this study shows that dynamic physiological load has the ability to repair the extracellular matrix depletion typical of early disc degeneration. PMID:24992586

  19. The elastic fibre network of the human lumbar anulus fibrosus: architecture, mechanical function and potential role in the progression of intervertebral disc degeneration

    PubMed Central

    Fazzalari, Nicola L.

    2009-01-01

    Elastic fibres are critical constituents of dynamic biological structures that functionally require elasticity and resilience. The network of elastic fibres in the anulus fibrosus of the intervertebral disc is extensive, however until recently, the majority of histological, biochemical and biomechanical studies have focussed on the roles of other extracellular matrix constituents such as collagens and proteoglycans. The resulting lack of detailed descriptions of elastic fibre network architecture and mechanical function has limited understanding of the potentially important contribution made by elastic fibres to healthy disc function and their possible roles in the progression of disc degeneration. In addition, it has made it difficult to postulate what the consequences of elastic fibre related disorders would be for intervertebral disc behaviour, and to develop treatments accordingly. In this paper, we review recent and historical studies which have examined both the structure and the function of the human lumbar anulus fibrosus elastic fibre network, provide a synergistic discussion in an attempt to clarify its potentially critical contribution both to normal intervertebral disc behaviour and the processes relating to its degeneration, and recommend critical areas for future research. PMID:19263091

  20. Thoracal flat back is a risk factor for lumbar disc degeneration after scoliosis surgery.

    PubMed

    Bernstein, Peter; Hentschel, Susanne; Platzek, Ivan; Hühne, Sebastian; Ettrich, Uwe; Hartmann, Albrecht; Seifert, Jens

    2014-06-01

    Lumbar segments below fused scoliotic spines are thought to be exposed to extraordinary stress. Although positive sagittal imbalance has come into focus, reports about factors influencing the outcome of these segments remain inconclusive. Our study aimed at identifying spinal risk factors for the development of lumbar degenerative disc disease (DDD) in surgically treated patients with adolescent idiopathic scoliosis (AIS). Retrospective comparative prognostic study (Level III) was conducted. Thirty-three patients were seen at an average follow-up of 7.5 years after either isolated selective anterior (n=18) or long combined anterior-posterior fusion (n=15) for AIS. Self-reported Scoliosis Research Society 22 questionnaire, physical examination including the detection of segmental pain and unspecific back pain, preoperative and postoperative whole-spine standing radiographs, and magnetic resonance imaging were obtained. Radiographic evaluation included the measurement of regional, coronal, and sagittal curve parameters and the assessment of spinal balance. Magnetic resonance imaging evaluation was done for preoperative and postoperative lumbar discs, according to the classification of Pfirrmann. Patients with low DDD (Pfirrmann grading <3) had a significantly higher thoracal kyphosis angle (mean 28°) than patients with advanced DDD (mean 15°). There was a trend toward a more flat-type lumbar lordosis in patients with severe DDD. Positive sagittal imbalance was associated with advanced DDD. Follow-up coronal parameters, trunk imbalance, instrumentation length, and lowest instrumented vertebra selection had no influence on DDD. Specific segmental pain could be attributed to a significantly higher coronal trunk imbalance (21 vs. 11 mm). This study establishes thoracal flat back as a risk factor for lumbar DDD after spinal fusion and supports the pathogenetic role of positive sagittal imbalance in this process. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Gene Therapy in the Retinal Degeneration Slow Model of Retinitis Pigmentosa

    PubMed Central

    Cai, Xue; Conley, Shannon M.; Naash, Muna I.

    2011-01-01

    Human blinding disorders are often initiated by hereditary mutations that insult rod and/or cone photoreceptors and cause subsequent cellular death. Generally, the disease phenotype can be predicted from the specific mutation as many photoreceptor genes are specific to rods or cones; however certain genes, such as Retinal Degeneration Slow (RDS), are expressed in both cell types and cause different forms of retinal disease affecting rods, cones, or both photoreceptors. RDS is a transmembrane glycoprotein critical for photoreceptor outer segment disc morphogenesis, structural maintenance, and renewal. Studies using animal models with Rds mutations provide valuable insight into Rds gene function and regulation; and a better understanding of the physiology, pathology, and underlying degenerative mechanisms of inherited retinal disease. Furthermore, these models are an excellent tool in the process of developing therapeutic interventions for the treatment of inherited retinal degenerations. In this paper, we review these topics with particular focus on the use of rds models in gene therapy. PMID:20238065

  2. IL-21 Is Positively Associated with Intervertebral Disc Degeneration by Interaction with TNF-α Through the JAK-STAT Signaling Pathway.

    PubMed

    Chen, Bin; Liu, Yi; Zhang, YuanQiang; Li, JingKun; Cheng, KaiYuan; Cheng, Lei

    2017-04-01

    This study was conducted in order to investigate the function of IL-21 in intervertebral disc degeneration. The serum concentration of IL-21 in patients with lumbar disc herniation (LDH) was examined by ELISA. Immunohistochemistry and western blot analysis were performed to detect the expression of IL-21, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-7), and tumor necrosis factor alpha (TNF-α) in degenerated intervertebral disc (IVD) tissues of human and rat. Moreover, nucleus pulposus (NP) cells were treated with 0, 10, 100, and 1000 ng/mL of IL-21 cytokine with and without AG490. TNF-α, ADAMTS-7, and matrix metalloproteinases-13 (MMP-13) mRNA expression was determined by RT-PCR. The expression of signal transducers and activators of transcription, STAT-1, STAT-3, and STAT-5b, was detected by western blot. IL-21 concentration level is higher in the degenerated group and positively correlates with the visual analog score (VAS). IL-21, ADAMTS-7, and TNF-α can be detected in the degenerative NP tissues in both human and rat degenerated NP tissues. The mRNA expression of ADAMTS-7, TNF-α, and MMP-13 was enhanced after stimulation with IL-21. Compared to control, STAT-1, STAT-3, and STAT-5b expression was also enhanced after IL-21 treatment, with STAT-3 being the most significantly enhanced; furthermore, expression was significantly reduced after treatment with AG490. The mRNA expression of TNF-α was markedly reduced after treatment with AG490 compared to treatment with IL-21 only. IL-21 is involved in the pathological development of IVD degeneration and IL-21 could aggravate IVD degeneration by stimulating TNF-α through the STAT signaling pathway.

  3. Modeling of rotating disc contactor (RDC) column

    NASA Astrophysics Data System (ADS)

    Ismail, Wan Nurul Aiffah; Zakaria, Siti Aisyah; Noor, Nor Fashihah Mohd; Sulong, Ibrahim; Arshad, Khairil Anuar

    2014-12-01

    Liquid-liquid extraction is one of the most important separation processes. Different kinds of liquid-liquid extractor such as Rotating Disc Contactor (RDC) Column being used in industries. The study of liquid-liquid extraction in an RDC column has become a very important subject to be discussed not just among chemical engineers but mathematician as well. In this research, the modeling of small diameter RDC column using the chemical system involving cumene/isobutryric asid/water are analyzed by the method of Artificial Neural Network (ANN). In the previous research, we begin the process of analyzed the data using methods of design of the experiments (DOE) to identify which factor and their interaction factor are significant and to determine the percentage of contribution of the variance for each factor. From the result obtained, we continue the research by discussed the development and validation of an artificial neural network model in estimating the concentration of continuous and concentration of dispersed outlet for an RDC column. It is expected that an efficient and reliable model will be formed to predict RDC column performance as an alternative to speed up the simulation process.

  4. Age-related accumulation of pentosidine in aggrecan and collagen from normal and degenerate human intervertebral discs.

    PubMed

    Sivan, Sarit Sara; Tsitron, Eve; Wachtel, Ellen; Roughley, Peter; Sakkee, Nico; van der Ham, Frits; Degroot, Jeroen; Maroudas, Alice

    2006-10-01

    During aging and degeneration, many changes occur in the structure and composition of human cartilaginous tissues, which include the accumulation of the AGE (advanced glycation end-product), pentosidine, in long-lived proteins. In the present study, we investigated the accumulation of pentosidine in constituents of the human IVD (intervertebral disc), i.e. collagen, aggrecan-derived PG (proteoglycan) (A1) and its fractions (A1D1-A1D6) in health and pathology. We found that, after maturity, pentosidine accumulates with age. Over the age range studied, a linear 6-fold increase was observed in pentosidine accumulation for A1 and collagen with respective rates of 0.12 and 0.66 nmol x (g of protein)(-1) x year(-1). Using previously reported protein turnover rate constants (k(T)) obtained from measurements of the D-isomer of aspartic residue in collagen and aggrecan of human IVD, we could calculate the pentosidine formation rate constants (k(F)) for these constituents [Sivan, Tsitron, Wachtel, Roughley, Sakkee, van der Ham, DeGroot, Roberts and Maroudas (2006) J. Biol. Chem. 281, 13009-13014; Tsitron (2006) MSc Thesis, Technion-Israel Institute of Technology, Haifa, Israel]. In spite of the comparable formation rate constants obtained for A1D1 and collagen [1.81+/-0.25 compared with 3.71+/-0.26 micromol of pentosidine x (mol of lysine)(-1) x year(-1) respectively], the higher pentosidine accumulation in collagen is consistent with its slower turnover (0.005 year(-1) compared with 0.134 year(-1) for A1D1). Pentosidine accumulation increased with decreasing buoyant density and decreasing turnover of the proteins from the most glycosaminoglycan-rich PG components (A1D1) to the least (A1D6), with respective k(F) values of 1.81+/-0.25 and 3.18+/-0.37 micromol of pentosidine.(mol of lysine)(-1) x year(-1). We concluded that protein turnover is an important determinant of pentosidine accumulation in aggrecan and collagen of human IVD, as was found for articular cartilage

  5. Kaempferol slows intervertebral disc degeneration by modifying LPS-induced osteogenesis/adipogenesis imbalance and inflammation response in BMSCs.

    PubMed

    Zhu, Jun; Tang, Haoyu; Zhang, Zhenhua; Zhang, Yong; Qiu, Chengfeng; Zhang, Ling; Huang, Pinge; Li, Feng

    2017-02-01

    Intervertebral disc (IVD) degeneration is a common disease that represents a significant cause of socio-economic problems. Bone marrow-derived mesenchymal stem cells (BMSCs) are a potential autologous stem cell source for the nucleus pulposus regeneration. Kaempferol has been reported to exert protective effects against both osteoporosis and obesity. This study explored the effect of kaempferol on BMSCs differentiation and inflammation. The results demonstrated that kaempferol did not show any cytotoxicity at concentrations of 20, 60 and 100μM. Kaempferol enhanced cell viability by counteracting the lipopolysaccharide (LPS)-induced cell apoptosis and increasing cell proliferation. Western blot analysis of mitosis-associated nuclear antigen (Ki67) and proliferation cell nuclear antigen (PCNA) further confirmed the increased effect of kaempferol on LPS-induced decreased viability of BMSCs. Besides, kaempferol elevated LPS-induced reduced level of chondrogenic markers (SOX-9, Collagen II and Aggrecan), decreased the level of matrix-degrading enzymes, i.e., matrix metalloprotease (MMP)-3 and MMP-13, suggesting the osteogenesis of BMSC under kaempferol treatment. On the other hand, kaempferol enhanced LPS-induced decreased expression of lipid catabolism-related genes, i.e., carnitine palmitoyl transferase-1 (CPT-1). Kaempferol also suppressed the expression of lipid anabolism-related genes, i.e., peroxisome proliferators-activated receptor-γ (PPAR-γ). The Oil red O staining further convinced the inhibition effect of kaempferol on BMSCs adipogenesis. In addition, kaempferol alleviated inflammatory by reducing the level of pro-inflammatory cytokines (i.e., interleukin (IL)-6) and increasing anti-inflammatory cytokine (IL-10) via inhibiting the nucleus translocation of nuclear transcription factor (NF)-κB p65. Taken together, our research indicated that kaempferol may serve as a novel target for treatment of IVD degeneration.

  6. TGFβ regulates Galectin-3 expression through canonical Smad3 signaling pathway in nucleus pulposus cells: implications in intervertebral disc degeneration.

    PubMed

    Tian, Ye; Yuan, Wen; Li, Jun; Wang, Hua; Hunt, Maxwell G; Liu, Chao; Shapiro, Irving M; Risbud, Makarand V

    2016-03-01

    Galectin-3 is highly expressed in notochordal nucleus pulposus (NP) and thought to play important physiological roles; however, regulation of its expression remains largely unexplored. The aim of the study was to investigate if TGFβ regulates Galectin-3 expression in NP cells. TGFβ treatment resulted in decreased Galectin-3 expression. Bioinformatic analysis using JASPAR and MatInspector databases cross-referenced with published ChIP-Seq data showed nine locations of highly probable Smad3 binding in the LGALS3 proximal promoter. In NP cells, TGFβ treatment resulted in decreased activity of reporters harboring several 5' deletions of the proximal Galectin-3 promoter. While transfection of NP cells with constitutively active (CA)-ALK5 resulted in decreased promoter activity, DN-ALK5 blocked the suppressive effect of TGFβ on the promoter. The suppressive effect of Smad3 on the Galectin-3 promoter was confirmed using gain- and loss-of-function studies. Transfection with DN-Smad3 or Smad7 blocked TGFβ mediated suppression of promoter activity. We also measured Galectin-3 promoter activity in Smad3 null and wild type cells. Noteworthy, promoter activity was suppressed by TGFβ only in wild type cells. Likewise, stable silencing of Smad3 in NP cells using sh-Smad3 significantly blocked TGFβ-dependent decrease in Galectin-3 expression. Treatment of human NP cells isolated from tissues with different grades of degeneration showed that Galectin-3 expression was responsive to TGF-β-mediated suppression. Importantly, Galectin-3 synergized effects of TNF-α on inflammatory gene expression by NP cells. Together these studies suggest that TGFβ, through Smad3 controls Galectin-3 expression in NP cells and may have implications in the intervertebral disc degeneration.

  7. Short Link N Stimulates Intervertebral Disc Repair in a Novel Long-Term Organ Culture Model that Includes the Bony Vertebrae.

    PubMed

    AlGarni, Nizar; Grant, Michael P; Epure, Laura M; Salem, Omar; Bokhari, Rakan; Antoniou, John; Mwale, Fackson

    2016-11-01

    Link N (DHLSDNYTLDHDRAIH) is a peptide that occurs naturally in the intervertebral discs (IVDs) and cartilage as a result of proteolytic cleavage of Link protein. Several studies have identified Link N as a growth factor capable of stimulating matrix synthesis in these tissues. We have recently discovered that annulus fibrosus cells can release an enzyme (possibly cathepsin K) that can further cleave Link N resulting in an eight amino acid peptide, we called short Link N (sLink N). Separately, we recently developed and validated an organ culture model that has the vertebrae attached (vIVDs; IVD with intact vertebrae). The aims of this study were (i) to examine if sLink N has the potential to repair early degenerate discs and (ii) to determine if this new model can be used to test potential drugs for disc repair. To determine if sLink N was able to stimulate repair of the degenerate disc, vIVDs with trypsin-induced degeneration (DG) were used. After 4 weeks of culture, the proteoglycan content measured as glycosaminoglycans was stimulated by sLink N in the degenerated discs, and the staining of proteoglycan was observed throughout the tissue irrespective of its proximity to the cells. The quantity of extractable type II collagen and aggrecan was also increased when the degenerate discs were treated with sLink N. Taken together, the results suggest that sLink N can increase key disc matrix molecules, namely type II collagen and aggrecan. Thus sLink N is an attractive peptide for tissue engineering and regeneration of the disc due to its anabolic effects. Finally, we show the feasibility of using the long-term whole organ culture system with adjacent intact vertebrae for studying the DG and regeneration of the IVD.

  8. A computational model for investigating the effects of changes in bioavailability of insulin-like growth factor-1 on the homeostasis of the intervertebral disc.

    PubMed

    Elmasry, Shady; Asfour, Shihab; de Rivero Vaccari, Juan Pablo; Travascio, Francesco

    2016-11-01

    Insulin-like growth factor-1 (IGF-1) is well-known for upregulating cell proliferation and biosynthesis of the extracellular matrix in the intervertebral disc (IVD). Pathological conditions, such as obesity or chronic kidney disease cause IGF-1 deficiency in plasma. How this deficiency impacts disc homeostasis remains unknown. Pro-anabolic approaches for the treatment of disc degeneration based on enhancing IGF-1 bioavailability to tissue-cells are considered, but knowledge of their effectiveness in enhancing cellular anabolism of a degenerated disc is limited. In this study, we developed a computational model for disc homeostasis specifically addressing the role of IGF-1 in modulating both extracellular matrix biosynthesis and cellularity in the IVD. This model was applied to investigate how changes in IGF-1 bioavailability, namely deficiency or enhancement of growth factor, affect disc health. In this study, it was found that IGF-1 deficiency mainly affects the biosynthesis of ECM components, especially in the most external regions of the IVD such as the cartilage endplates and the outer portion of annulus fibrosus. Also, a total of three approaches for increasing IGF-1 bioavailability as a therapy for degenerated IVDs were investigated. It was found that all these strategies are only beneficial to those disc regions receiving sufficient nutritional supply (i.e., the outmost IVD regions), while they exacerbate tissue degradation in malnourished regions (i.e., inner portion of the disc). This suggests that pro-anabolic growth factor-based therapies are limited in that their success strongly depends on an adequate nutritional supply to the IVD tissue, which is not guaranteed in degenerated discs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Gas Modelling in the Disc of HD 163296

    NASA Technical Reports Server (NTRS)

    Tilling, I.; Woitke, P.; Meeus, G.; Mora, A.; Montesinos, B.; Riviere-Marichalar, P.; Eiroa, C.; Thi, W. -F.; Isella, A.; Roberge, A.; Martin-Zaidi, C.; Kamp, I.; Pinte, C.; Sandell, G.; Vacca, W. D.; Menard, F.; Mendigutia, I.; Duchene, G.; Dent, W. R. F.; Aresu, G.; Meijerink, R.; Spaans, M.

    2011-01-01

    We present detailed model fits to observations of the disc around the Herbig Ae star HD 163296. This well-studied object has an age of approx. 4Myr, with evidence of a circumstellar disc extending out to approx. 540AU. We use the radiation thermo-chemical disc code ProDiMo to model the gas and dust in the circumstellar disc of HD 163296, and attempt to determine the disc properties by fitting to observational line and continuum data. These include new Herschel/PACS observations obtained as part of the open-time key program GASPS (Gas in Protoplanetary Systems), consisting of a detection of the [Oi] 63 m line and upper limits for several other far infrared lines. We complement this with continuum data and ground-based observations of the CO-12 3-2, 2-1 and CO-13 J=1-0 line transitions, as well as the H2 S(1) transition. We explore the effects of stellar ultraviolet variability and dust settling on the line emission, and on the derived disc properties. Our fitting efforts lead to derived gas/dust ratios in the range 9-100, depending on the assumptions made. We note that the line fluxes are sensitive in general to the degree of dust settling in the disc, with an increase in line flux for settled models. This is most pronounced in lines which are formed in the warm gas in the inner disc, but the low excitation molecular lines are also affected. This has serious implications for attempts to derive the disc gas mass from line observations. We derive fractional PAH abundances between 0.007 and 0.04 relative to ISM levels. Using a stellar and UV excess input spectrum based on a detailed analysis of observations, we find that the all observations are consistent with the previously assumed disc geometry

  10. Genetic Polymorphisms of Interleukin-1 Alpha and the Vitamin D Receptor in Mexican Mestizo Patients with Intervertebral Disc Degeneration

    PubMed Central

    Cervin Serrano, Salvador; González Villareal, Dalia; Aguilar-Medina, Maribel; Romero-Navarro, Jose Guillermo; Romero Quintana, Jose Geovanni; Arámbula Meraz, Eliakym; Osuna Ramírez, Ignacio; Picos-Cárdenas, Veronica; Granados, Julio; Estrada-García, Iris; Sánchez-Schmitz, Guzman; Ramos-Payán, Rosalío

    2014-01-01

    Intervertebral disc degeneration (IDD) is the most common diagnosis in patients with back pain, a leading cause of musculoskeletal disability worldwide. Several conditions, such as occupational activities, gender, age, and obesity, have been associated with IDD. However, the development of this disease has strong genetic determinants. In this study, we explore the possible association between rs1800587 (c.-949C>T) of interleukin-1 alpha (IL1A) and rs2228570 (c.2T>V) and rs731236 (c.1056T>C) of vitamin D receptor (VDR) gene polymorphisms and the development of IDD in northwestern Mexican Mestizo population. Gene polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by age and gender: patients with symptomatic lumbar IDD (n = 100) and subjects with normal lumbar-spine MRI-scans (n = 100). Distribution of the mutated alleles in patients and controls was 27.0% versus 28.0% (P = 0.455) for T of rs1800587 (IL1A); 53.0% versus 58.0% (P = 0.183) for V of rs2228570 (VDR); and 18.0% versus 21.0% (P = 0.262) for C of rs731236 (VDR). Our results showed no association between the studied polymorphisms and IDD in this population. This is the first report on the contribution of gene polymorphisms on IDD in a Mexican population. PMID:25506053

  11. Genetic polymorphisms of interleukin-1 alpha and the vitamin d receptor in mexican mestizo patients with intervertebral disc degeneration.

    PubMed

    Cervin Serrano, Salvador; González Villareal, Dalia; Aguilar-Medina, Maribel; Romero-Navarro, Jose Guillermo; Romero Quintana, Jose Geovanni; Arámbula Meraz, Eliakym; Osuna Ramírez, Ignacio; Picos-Cárdenas, Veronica; Granados, Julio; Estrada-García, Iris; Sánchez-Schmitz, Guzman; Ramos-Payán, Rosalío

    2014-01-01

    Intervertebral disc degeneration (IDD) is the most common diagnosis in patients with back pain, a leading cause of musculoskeletal disability worldwide. Several conditions, such as occupational activities, gender, age, and obesity, have been associated with IDD. However, the development of this disease has strong genetic determinants. In this study, we explore the possible association between rs1800587 (c.-949C>T) of interleukin-1 alpha (IL1A) and rs2228570 (c.2T>V) and rs731236 (c.1056T>C) of vitamin D receptor (VDR) gene polymorphisms and the development of IDD in northwestern Mexican Mestizo population. Gene polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by age and gender: patients with symptomatic lumbar IDD (n = 100) and subjects with normal lumbar-spine MRI-scans (n = 100). Distribution of the mutated alleles in patients and controls was 27.0% versus 28.0% (P = 0.455) for T of rs1800587 (IL1A); 53.0% versus 58.0% (P = 0.183) for V of rs2228570 (VDR); and 18.0% versus 21.0% (P = 0.262) for C of rs731236 (VDR). Our results showed no association between the studied polymorphisms and IDD in this population. This is the first report on the contribution of gene polymorphisms on IDD in a Mexican population.

  12. Bioinformatics analysis of molecular mechanisms involved in intervertebral disc degeneration induced by TNF-α and IL-1β.

    PubMed

    Xu, Feng; Gao, Feng; Liu, Yadong; Wang, Zhenyu; Zhuang, Xinming; Qu, Zhigang; Ma, Hui; Liu, Yi; Fu, Changfeng; Zhang, Qi; Duan, Xiaoying

    2016-03-01

    The present study aimed to explore the molecular mechanisms associated with intervertebral disc degeneration (IDD) induced by tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β. The microarray dataset no. GSE42611 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between four experimental nucleus pulposus samples and four control nucleus pulposus samples were analyzed. Subsequently, Gene Ontology (GO) and pathway enrichment analyses of DEGs were performed, followed by protein‑protein interaction (PPI) network construction and prediction of a regulatory network of transcription factor (TFs). Finally, the transcriptional regulatory network was integrated into the PPI network to analyze the network modules. A total of 246 upregulated and 290 downregulated DEGs were identified. The upregulated DEGs were mainly associated with GO terms linked with inflammatory response and apoptotic pathways, while the downregulated DEGs were mainly associated with GO terms linked with cell adhesion and pathways of extracellular matrix ‑ receptor interaction. In the PPI network, IL6, COL1A1, NFKB1 and HIF1A were hub genes, and in addition, NFKB1 and HIF1A were TFs. Pathways of apoptosis and extracellular matrix ‑ receptor interaction may have important roles in IDD progression. IL6, COL1A1 and the TFs NFKB1 and HIF1A may be used as biomarkers for IDD diagnosis and treatment.

  13. Parametric modeling of the intervertebral disc space in 3D: application to CT images of the lumbar spine.

    PubMed

    Korez, Robert; Likar, Boštjan; Pernuš, Franjo; Vrtovec, Tomaž

    2014-10-01

    Gradual degeneration of intervertebral discs of the lumbar spine is one of the most common causes of low back pain. Although conservative treatment for low back pain may provide relief to most individuals, surgical intervention may be required for individuals with significant continuing symptoms, which is usually performed by replacing the degenerated intervertebral disc with an artificial implant. For designing implants with good bone contact and continuous force distribution, the morphology of the intervertebral disc space and vertebral body endplates is of considerable importance. In this study, we propose a method for parametric modeling of the intervertebral disc space in three dimensions (3D) and show its application to computed tomography (CT) images of the lumbar spine. The initial 3D model of the intervertebral disc space is generated according to the superquadric approach and therefore represented by a truncated elliptical cone, which is initialized by parameters obtained from 3D models of adjacent vertebral bodies. In an optimization procedure, the 3D model of the intervertebral disc space is incrementally deformed by adding parameters that provide a more detailed morphometric description of the observed shape, and aligned to the observed intervertebral disc space in the 3D image. By applying the proposed method to CT images of 20 lumbar spines, the shape and pose of each of the 100 intervertebral disc spaces were represented by a 3D parametric model. The resulting mean (±standard deviation) accuracy of modeling was 1.06±0.98mm in terms of radial Euclidean distance against manually defined ground truth points, with the corresponding success rate of 93% (i.e. 93 out of 100 intervertebral disc spaces were modeled successfully). As the resulting 3D models provide a description of the shape of intervertebral disc spaces in a complete parametric form, morphometric analysis was straightforwardly enabled and allowed the computation of the corresponding

  14. Degenerated intervertebral disc prolapse and its association of collagen I alpha 1 Spl gene polymorphism: A preliminary case control study of Indian population

    PubMed Central

    Anjankar, Shailendra D; Poornima, Subhadra; Raju, Subodh; Jaleel, MA; Bhiladvala, Dilnavaz; Hasan, Qurratulain

    2015-01-01

    Background: Degenerated disc disease (DDD) is a common disorder responsible for increased morbidity in a productive age group. Its etiology is multifactorial and genetic factors have been predominantly implicated. Disc prolapse results due to tear in the annulus, which is a fibrous structure composed largely of type I collagen. Functional polymorphism at the Sp1 site of the collagen I alpha 1 (COL1A1) gene has shown a positive association with DDD in Dutch and Greek populations. The purpose of this study was to assess COL1A1 Sp1 gene polymorphism in the Indian population. Materials and Methods: Fifty clinically and radiologically proven patients with disc prolapse requiring surgery were included as cases and 50 healthy, age-matched volunteers served as controls. After isolating DNA from their blood sample, genotyping for COL1A1 polymorphism (rs1800012) was performed and identified as GG, GT, and TT. Results: The mean age and body mass index in cases and controls were similar. 76% of the patients were males. The most common site of disc degeneration was L4–L5 (36%), followed by L5–S1 (34%). Homozygous–GG, heterozygous GT, and homozygous TT genotypes were seen in 38 (76%), 10 (20%) and 2 (4%) cases respectively, controls had similar percentage of genotypes as well. The alleles in cases and the control group showed no significant difference (P = 0.6744) and followed the Hardy–Weinberg Equilibrium in the study population. Conclusion: The COL1A1 (rs1800012) is in Hardy–Weinberg equilibrium in the present subset of Indian population. But taken as a single factor, it was not found to be associated with DDD in this preliminary study. Disc degeneration is multifactorial and also anticipated to be a result of multiple genes involvement and gene-gene interaction. PMID:26806964

  15. A novel rat model with obesity-associated retinal degeneration.

    PubMed

    Reddy, Geereddy Bhanuprakash; Vasireddy, Vidyullatha; Mandal, Md Nawajes A; Tiruvalluru, Mrudula; Wang, Xiaofei F; Jablonski, Monica M; Nappanveettil, Giridharan; Ayyagari, Radha

    2009-07-01

    A strong association between retinal degeneration and obesity has been shown in humans. However, the molecular basis of increased risk for retinal degeneration in obesity is unknown. Thus, an animal model with obesity and retinal degeneration would greatly aid the understanding of obesity-associated retinal degeneration. The retinal abnormalities in a novel rat model (WNIN-Ob) with spontaneously developed obesity are described. Histologic and immunohistochemical examination were performed on retinal sections of 2- to 12-month-old WNIN-Ob rats, and findings were compared with those of lean littermate controls. RNA from retinas of 12-month-old WNIN-Ob and lean littermate rats was used for microarray and qRT-PCR analysis. The WNIN-Ob rats developed severe obesity, with an onset at approximately 35 days. Evaluation of retinal morphology in 2- to 12-month-old WNIN-Ob and age-matched lean littermate controls revealed progressive retinal degeneration, with an onset between 4 to 6 months of age. Immunohistochemical analysis with anti-rhodopsin, anti-cone opsin, and PSD-95 antibodies further confirmed retinal degeneration, particularly rod cell loss and thinner outer plexiform layer, in the obese rat retina. Gene expression by microarray analysis and qRT-PCR established activation of stress response, tissue remodeling, impaired phototransduction, and photoreceptor degeneration in WNIN-Ob rat retina. WNIN-Ob rats develop increased stress in retinal tissue and progressive retinal degeneration after the onset of severe obesity. The WNIN-Ob rat is the first rat model to develop retinal degeneration after the onset of obesity. This novel rat model may be a valuable tool for investigating retinal degeneration associated with obesity in humans.

  16. Body mass index is associated with lumbar disc degeneration in young Finnish males: subsample of Northern Finland birth cohort study 1986

    PubMed Central

    2013-01-01

    Background The role of environmental factors in lumbar intervertebral disc degeneration (DD) in young adults is largely unknown. Therefore, we investigated whether body mass index (BMI), smoking, and physical activity are associated with lumbar DD among young adults. Methods The Oulu Back Study (OBS) is a subpopulation of the 1986 Northern Finland Birth Cohort (NFBC 1986) and it originally included 2,969 children. The OBS subjects received a postal questionnaire, and those who responded (N = 1,987) were invited to the physical examination. The participants (N = 874) were invited to lumbar MRI study. A total of 558 young adults (325 females and 233 males) underwent MRI that used a 1.5-T scanner at the mean age of 21. Each lumbar intervertebral disc was graded as normal (0), mildly (1), moderately (2), or severely (3) degenerated. We calculated a sum score of the lumbar DD, and analyzed the associations between environmental risk factors (smoking, physical activity and weight-related factors assessed at 16 and 19 years) and DD using ordinal logistic regression, the results being expressed as cumulative odds ratios (COR). All analyses were stratified by gender. Results Of the 558 subjects, 256 (46%) had no DD, 117 (21%) had sum score of one, 93 (17%) sum score of two, and 92 (17%) sum score of three or higher. In the multivariate ordinal logistic regression model, BMI at 16 years (highest vs. lowest quartile) was associated with DD sum score among males (COR 2.35; 95% CI 1.19-4.65) but not among females (COR 1.29; 95% CI 0.72-2.32). Smoking of at least four pack-years was associated with DD among males, but not among females (COR 2.41; 95% CI 0.99-5.86 and 1.59; 95% 0.67-3.76, respectively). Self-reported physical activity was not associated with DD. Conclusions High BMI at 16 years was associated with lumbar DD at 21 years among young males but not among females. High pack-years of smoking showed a comparable association in males, while physical activity had

  17. [Assessment of the correlation between histological degeneration and radiological and clinical parameters in a series of patients who underwent lumbar disc herniation surgery].

    PubMed

    Munarriz, Pablo M; Paredes, Igor; Alén, José F; Castaño-Leon, Ana M; Cepeda, Santiago; Hernandez-Lain, Aurelio; Lagares, Alfonso

    2017-09-26

    The use of histological degeneration scores in surgically-treated herniated lumbar discs is not common in clinical practice and its use has been primarily restricted to research. The objective of this study is to evaluate if there is an association between a higher grade of histological degeneration when compared with clinical or radiological parameters. Retrospective consecutive analysis of 122 patients who underwent single-segment lumbar disc herniation surgery. Clinical information was available on all patients, while the histological study and preoperative magnetic resonance imaging were also retrieved for 75 patients. Clinical variables included age, duration of symptoms, neurological deficits, or affected deep tendon reflex. The preoperative magnetic resonance imaging was evaluated using Modic and Pfirrmann scores for the affected segment by 2 independent observers. Histological degeneration was evaluated using Weiler's score; the presence of inflammatory infiltrates and neovascularization, not included in the score, were also studied. Correlation and chi-square tests were used to assess the association between histological variables and clinical or radiological variables. Interobserver agreement was also evaluated for the MRI variables using weighted kappa. No statistically significant correlation was found between histological variables (histological degeneration score, inflammatory infiltrates or neovascularization) and clinical or radiological variables. Interobserver agreement for radiological scores resulted in a kappa of 0.79 for the Pfirrmann scale and 0.65 for the Modic scale, both statistically significant. In our series of patients, we could not demonstrate any correlation between the degree of histological degeneration or the presence of inflammatory infiltrates when compared with radiological degeneration scales or clinical variables such as the patient's age or duration of symptoms. Copyright © 2017 Sociedad Española de Neurocirug

  18. OPG rs2073617 polymorphism is associated with upregulated OPG protein expression and an increased risk of intervertebral disc degeneration

    PubMed Central

    Xue, Jing-Bo; Zhan, Xin-Li; Wang, Wen-Jun; Yan, Yi-Guo; Liu, Chong

    2016-01-01

    The present study aimed to investigate the associations between three distinct osteoprotegerin (OPG) gene polymorphisms and the risk of intervertebral disc degeneration (IDD). A total of 200 IDD patients and 200 healthy controls were recruited from the Department of Spine Surgery at the First Affiliated Hospital of the University of South China (Hengyang, China) between January 2013 and May 2014. The allele, genotype and haplotype frequency distributions of three OPG polymorphisms in the study and control populations were analyzed by polymerase chain reaction prior to restriction fragment length polymorphism or high resolution melting assays. In addition, serum OPG levels were measured via an ELISA. The genotype and allele frequencies of the OPG rs2073617 polymorphisms were significantly higher in the IDD patients, as compared with the control group (P<0.05). Furthermore, carriers of the C allele exhibited a higher risk of IDD, as compared with carriers of the T allele (P<0.001). Conversely, the genotype and allele frequencies of the two other gene polymorphisms, rs2073618 and rs3102735, showed no significant differences between the patients and controls (P>0.05). The serum OPG levels were significantly higher in IDD patients with TT, TC and CC genotypes at the OPG rs2073617 polymorphism, as compared with the control group (P<0.05). Logistic-regression analysis suggested that high serum levels of OPG were positively correlated with IDD risk, whereas the T-C-A, T-G-A and T-G-G haplotypes were negatively correlated with IDD risk (P<0.05). Furthermore, the G-T-G haplotype was associated with protection against IDD (P=0.008), whereas the G-C-G haplotype was associated with an elevated susceptibility to IDD (P=0.007). The results of the present study suggested that OPG rs2073617 polymorphisms and upregulated serum levels of OPG were associated with an increased risk of IDD, whereas the T-C-A, T-G-A and T-G-G haplotypes were protective factors for IDD. The results of the

  19. Notochordal cells protect nucleus pulposus cells from degradation and apoptosis: implications for the mechanisms of intervertebral disc degeneration

    PubMed Central

    2011-01-01

    Introduction The relative resistance of non-chondrodystrophic (NCD) canines to degenerative disc disease (DDD) may be due to a combination of anabolic and anti-catabolic factors secreted by notochordal cells within the intervertebral disc (IVD) nucleus pulposus (NP). Factors known to induce DDD include interleukin-1 beta (IL-1ß) and/or Fas-Ligand (Fas-L). Therefore we evaluated the ability of notochordal cell conditioned medium (NCCM) to protect NP cells from IL-1ß and IL-1ß +FasL-mediated cell death and degeneration. Methods We cultured bovine NP cells with IL-1ß or IL-1ß+FasL under hypoxic serum-free conditions (3.5% O2) and treated the cells with either serum-free NCCM or basal medium (Advanced DMEM/F-12). We used flow cytometry to evaluate cell death and real-time (RT-)PCR to determine the gene expression of aggrecan, collagen 2, and link protein, mediators of matrix degradation ADAMTS-4 and MMP3, the matrix protection molecule TIMP1, the cluster of differentiation (CD)44 receptor, the inflammatory cytokine IL-6 and Ank. We then determined the expression of specific apoptotic pathways in bovine NP cells by characterizing the expression of activated caspases-3, -8 and -9 in the presence of IL-1ß+FasL when cultured with NCCM, conditioned medium obtained using bovine NP cells (BCCM), and basal medium all supplemented with 2% FBS. Results NCCM inhibits bovine NP cell death and apoptosis via suppression of activated caspase-9 and caspase-3/7. Furthermore, NCCM protects NP cells from the degradative effects of IL-1ß and IL-1ß+Fas-L by up-regulating the expression of anabolic/matrix protective genes (aggrecan, collagen type 2, CD44, link protein and TIMP-1) and down-regulating matrix degrading genes such as MMP-3. Expression of ADAMTS-4, which encodes a protein for aggrecan remodeling, is increased. NCCM also protects against IL-1+FasL-mediated down-regulation of Ank expression. Furthermore, NP cells treated with NCCM in the presence of IL-1ß+Fas-L down

  20. The Effect of Gamma Irradiation on the Biological Properties of Intervertebral Disc Allografts: In Vitro and In Vivo Studies in a Beagle Model

    PubMed Central

    Ding, Yu; Ruan, Dike; Luk, Keith D. K.; He, Qing; Wang, Chaofeng

    2014-01-01

    Study Design An animal experiment about intervertebral disc allograft. Objective To explore the feasibility to decellularize disc allografts treated by 6°Co Gamma Irradiation, and simultaneously, to assess the possibility to make use of the decellularized natural disc scaffold for disc degeneration biotherapy. Summary of Background Data Studies of both animal and human disc allograft transplantation indicated that the disc allograft may serve as a scaffold to undertake the physiological responsibility of the segment. Methods Experiment in vitro: 48 discs of beagles were harvested and divided randomly into four groups including a control group and three irradiated groups. Immediate cell viability and biomechanical properties of the discs were checked and comparisons were made among these groups. Experiment in vivo: 24 beagles accepted single-level allografted disc treated with different doses of gamma irradiation. Plain X-rays and MRIs were taken before and after surgery. Then, the spinal columns were harvested en bloc from the sacrificed beagles and were examined morphologically. Results There were significant differences of both the annulus fibrosus and nucleus pulposus immediate cell viabilities among the various groups. There were no obvious differences of the biomechanical properties among the four groups. The disc height and range of motion decreased significantly in all groups as time went on. The observed indexes in irradiated groups were much smaller than those in the control group, but the indexes in 18-kGy group were larger than those in 25-kGy and 50-kGy groups. Both MRI and macroscopic findings showed that the segmental degeneration in the control and 18-kGy group was less severe than that in 25-kGy and 50-kGy groups. Conclusion Gamma Irradiation can decellularize disc allograft successfully to provide natural scaffold for the study of degenerative disc disease therapy, and also can be used as an effective method to produce adjustable animal models

  1. The Effect of Substance P on an Intervertebral Disc Rat Organ Culture Model.

    PubMed

    Koerner, John D; Markova, Dessislava Z; Schroeder, Gregory D; Rihn, Jeffery A; Hilibrand, Alan S; Vaccaro, Alexander R; Anderson, D Greg; Kepler, Christopher K

    2016-12-15

    Laboratory study. Evaluate the effect of substance P (SP) on an intervertebral disc rat organ culture model. Monolayer cell experiments have demonstrated that exposure intervertebral disc tissue cells to SP leads to upregulation in inflammatory cytokine expression; however, this has not been evaluated in a more complex organ culture model. Forty-eight intervertebral discs from eight rats were used in an organ culture model. Intervertebral discs were divided into three groups: control, SP-treated group, and a group treated with an SP antagonist followed by SP. Cytokine antibody array was used to quantify expression patterns, which were confirmed using ELISA and real-time polymerase chain reaction. The cytokine array demonstrated a 3.40 ±  0.59-fold increase in interleukin 6 (IL-6) expression in the SP group (P = 0.004), and the effect of SP was mitigated by the SP antagonist (P = 0.03). These results were verified as ELISA demonstrated a significant difference in the IL-6 level between the control group and SP group (0.73 vs. 5.80 ng/mL, P < 0.001), and there was a significant difference in the IL-6 level between the SP and the SP antagonist group (5.80 vs. 4.02 ng/mL, P = 0.01). Similarly, the real-time polymerase chain reaction demonstrated that the discs treated with SP had a 4.77-fold increase in IL-6 levels (P = 0.01) compared to controls, and a significantly greater increase in IL-6 levels between the intervertebral discs in the SP group and those in the SP antagonist group versus control (4.77 vs. 1.57, P = 0.02). SP lead to the activation of an inflammatory pathway by increasing expression of IL-6 in an intervertebral disc organ culture model. These results provide evidence that SP may be an important factor in the link between intervertebral disc degeneration and low back pain. N/A.

  2. Mutation of a Drosophila gamma tubulin ring complex subunit encoded by discs degenerate-4 differentially disrupts centrosomal protein localization

    PubMed Central

    Barbosa, Vitor; Yamamoto, Rochele R.; Henderson, Daryl S.; Glover, David M.

    2000-01-01

    We have cloned the Drosophila gene discs degenerate-4 (dd4) and find that it encodes a component of the γ-tubulin ring complex (γTuRC) homologous to Spc98 of budding yeast. This provides the first opportunity to study decreased function of a member of the γ-tubulin ring complex, other than γ-tubulin itself, in a metazoan cell. γ-tubulin is no longer at the centrosomes but is dispersed throughout dd4 cells and yet bipolar metaphase spindles do form, although these have a dramatically decreased density of microtubules. Centrosomin (CNN) remains in broad discrete bodies but only at the focused poles of such spindles, whereas Asp (abnormal spindle protein) is always present at the presumptive minus ends of microtubules, whether or not they are focused. This is consistent with the proposed role of Asp in coordinating the nucleation of mitotic microtubule organizing centers. The centrosome associated protein CP190 is partially lost from the spindle poles in dd4 cells supporting a weak interaction with γ-tubulin, and the displaced protein accumulates in the vicinity of chromosomes. Electron microscopy indicates not only that the poles of dd4 cells have irregular amounts of pericentriolar material, but also that they can have abnormal centrioles. In six dd4 cells subjected to serial sectioning centrioles were missing from one of the two poles. This suggests that in addition to its role in nucleating cytoplasmic and spindle microtubules, the γTuRC is also essential to the structure of centrioles and the separation of centrosomes. PMID:11124805

  3. Biological Behavior of Human Nucleus Pulposus Mesenchymal Stem Cells in Response to Changes in the Acidic Environment During Intervertebral Disc Degeneration.

    PubMed

    Liu, Jianjun; Tao, Hui; Wang, Hanbang; Dong, Fulong; Zhang, Renjie; Li, Jie; Ge, Peng; Song, Peiwen; Zhang, Huaqing; Xu, Peng; Liu, Xiaoying; Shen, Cailiang

    2017-06-15

    An acidic environment is vital for the maintenance of cellular activities but can be affected tremendously during intervertebral disc degeneration (IVDD). The effect of changes in the acidity of the environment on human nucleus pulposus mesenchymal stem cells (NP-MSCs) is, however, unknown. Thus, this study aimed to observe the biological effects of acidic conditions mimicking a degenerated intervertebral disc on NP-MSCs in vitro. NP-MSCs were isolated from patients with lumbar disc herniation and were further identified by their immunophenotypes and multilineage differentiation. Then, cells were cultured at acidic pH levels (pH 6.2, pH 6.5, pH 6.8, pH 7.1, and pH 7.4) with/without amiloride, an acid-sensing ion channel (ASIC) blocker. The proliferation and apoptosis of NP-MSCs and the expression of stem cell-related genes (Oct4, Nanog, Jagged, Notch1), ASICs, and functional genes (Aggrecan, SOX-9, Collagen-I, and Collagen-II) in NP-MSCs were evaluated. Our work showed that cells obtained from human degenerated NP met the criteria of International Society for Cellular Therapy. Therefore, cells obtained from a degenerated nucleus pulposus were definitively identified as NP-MSCs. Our results also indicated that acidic conditions could significantly inhibit cell proliferation and increase cell apoptosis. Gene expression results demonstrated that acidic conditions could decrease the expression of stem cell-related genes and inhibit extracellular matrix synthesis, whereas it could increase the expression of ASICs. Our study further verified that the above-mentioned biological activities of NP-MSCs could be significantly improved by amiloride. Therefore, the results of the study indicated that the biological behavior of NP-MSCs could be inhibited by acidic conditions during IVDD, and amiloride may meliorate IVDD by improving the activities of NP-MSCs.

  4. Spinning disc atomisation process: Modelling and computations

    NASA Astrophysics Data System (ADS)

    Li, Yuan; Sisoev, Grigory; Shikhmurzaev, Yulii

    2016-11-01

    The atomisation of liquids using a spinning disc (SDA), where the centrifugal force is used to generate a continuous flow, with the liquid eventually disintegrating into drops which, on solidification, become particles, is a key element in many technologies. Examples of such technologies range from powder manufacturing in metallurgy to various biomedical applications. In order to be able to control the SDA process, it is necessary to understand it as a whole, from the feeding of the liquid and the wave pattern developing on the disc to the disintegration of the liquid film into filaments and these into drops. The SDA process has been the subject of a number of experimental studies and some elements of it, notably the film on a spinning disc and the dynamics of the jets streaming out from it, have been investigated theoretically. However, to date there have been no studies of the process as a whole, including, most importantly, the transition zone where the film that has already developed a certain wave pattern disintegrates into jets that spiral out. The present work reports some results of an ongoing project aimed at producing a definitive map of regimes occurring in the SDA process and their outcome.

  5. In vitro assessment of biomaterial-induced remodeling of subchondral and cancellous bone for the early intervention of joint degeneration with focus on the spinal disc

    NASA Astrophysics Data System (ADS)

    McCanless, Jonathan D.

    Osteoarthritis-associated pain of the spinal disc, knee, and hip derives from degeneration of cartilagenous tissues in these joints. Traditional therapies have focused on these cartilage (and disc specific nucleus pulposus) changes as a means of treatment through tissue grafting, regenerative synthetic implants, non-regenerative space filling implants, arthroplasty, and arthrodesis. Although such approaches may seem apparent upon initial consideration of joint degeneration, tissue pathology has shown changes in the underlying bone and vascular bed precede the onset of cartilaginous changes. It is hypothesized that these changes precedent joint degeneration and as such may provide a route for early prevention. The current work proposes an injectable biomaterial-based therapy within these subchondral and cancellous bone regions as a means of preventing or reversing osteoarthritis. Two human concentrated platelet releasate-containing alginate hydrogel/beta-tricalcium phosphate composites have been developed for this potential biomaterial application. The undertaking of assessing these materials through bench-, in vitro, and ex vivo work is described herein. These studies showed the capability of the biomaterials to initiate a wound healing response in monocytes, angiogenic and differentiation behavior in immature endothelial cells, and early osteochondral differentiation in mesenchymal stem cells. These cellular activities are associated with fracture healing and endochondral bone formation, demonstrating the potential of the biomaterials to induce osseous and vascular tissue remodeling underlying osteoarthritic joints as a novel therapy for a disease with rapidly growing healthcare costs.

  6. Drosophila melanogaster as a Model of Muscle Degeneration Disorders.

    PubMed

    Kreipke, R E; Kwon, Y V; Shcherbata, H R; Ruohola-Baker, H

    2017-01-01

    Drosophila melanogaster provides a powerful platform with which researchers can dissect complex genetic questions and biochemical pathways relevant to a vast array of human diseases and disorders. Of particular interest, much work has been done with flies to elucidate the molecular mechanisms underlying muscle degeneration diseases. The fly is particularly useful for modeling muscle degeneration disorders because there are no identified satellite muscle cells to repair adult muscle following injury. This allows for the identification of endogenous processes of muscle degeneration as discrete events, distinguishable from phenotypes due to the lack of stem cell-based regeneration. In this review, we will discuss the ways in which the fruit fly provides a powerful platform with which to study human muscle degeneration disorders.

  7. Polarimetric Models of Circumstellar Discs Including Aggregate Dust Grains

    NASA Astrophysics Data System (ADS)

    Mohan, Mahesh

    The work conducted in this thesis examines the nature of circumstellar discs by investigating irradiance and polarization of scattered light. Two circumstellar discs are investigated. Firstly, H-band high contrast imaging data on the transitional disc of the Herbig Ae/Be star HD169142 are presented. The images were obtained through the polarimetric differential imaging (PDI) technique on the Very Large Telescope (VLT) using the adaptive optics system NACO. Our observations use longer exposure times, allowing us to examine the edges of the disc. Analysis of the observations shows distinct signs of polarization due to circumstellar material, but due to excessive saturation and adaptive optics errors further information on the disc could not be inferred. The HD169142 disc is then modelled using the 3D radiative transfer code Hyperion. Initial models were constructed using a two disc structure, however recent PDI has shown the existence of an annular gap. In addition to this the annular gap is found not to be devoid of dust. This then led to the construction of a four-component disc structure. Estimates of the mass of dust in the gap (2.10E-6 Msun) are made as well as for the planet (1.53E-5 Msun (0.016 Mjupiter)) suspected to be responsible for causing the gap. The predicted polarization was also estimated for the disc, peaking at ~14 percent. The use of realistic dust grains (ballistic aggregate particles) in Monte Carlo code is also examined. The fortran code DDSCAT is used to calculate the scattering properties for aggregates which are used to replace the spherical grain models used by the radiative transfer code Hyperion. Currently, Hyperion uses four independent elements to define the scattering matrix, therefore the use of rotational averaging and a 50/50 percent population of grains and their enantiomers were explored to reduce the number of contributing scattering elements from DDSCAT. A python script was created to extract the scattering data from the DDSCAT

  8. Immunomorphological analysis of RAGE receptor expression and NF-kappaB activation in tissue samples from normal and degenerated intervertebral discs of various ages.

    PubMed

    Nerlich, Andreas G; Bachmeier, Beatrice E; Schleicher, Erwin; Rohrbach, Helmut; Paesold, Guenther; Boos, Norbert

    2007-01-01

    We immunohistochemically investigated the pattern of RAGE expression and NFkappaB translocation into the nucleus in 43 complete cross-sections of human lumbar intervertebral discs (neonatal-85 years) and compared this with the carboxymethyl-lysine (CML) modification of proteins as a marker for oxidative stress. No significant expression of RAGE, no obvious activation of NF-kappaB, and no deposition of CML-modified proteins were seen in fetal, juvenile, and young adolescent discs (until age of 13 years). In adults, 25-50% of nucleus pulposus cells were labeled for RAGE and activated NF-kappaB, which correlated well with the occurrence and extent of CML staining in the pericellular matrix. In the annulus fibrosus significantly lower values were seen than in the nucleus pulposus. In consequence, we provide evidence for activation of the NF-kappaB system in intervertebral discs in vivo, which correlates with accumulated oxidative stress and increases in age and disc degeneration. Oxidative stress (as monitored by CML modifications) may lead to RAGE activation and NF-kappaB translocation.

  9. Development of Animal Models of Local Retinal Degeneration

    PubMed Central

    Lorach, Henri; Kung, Jennifer; Beier, Corinne; Mandel, Yossi; Dalal, Roopa; Huie, Philip; Wang, Jenny; Lee, Seungjun; Sher, Alexander; Jones, Bryan William; Palanker, Daniel

    2015-01-01

    Purpose Development of nongenetic animal models of local retinal degeneration is essential for studies of retinal pathologies, such as chronic retinal detachment or age-related macular degeneration. We present two different methods to induce a highly localized retinal degeneration with precise onset time, that can be applied to a broad range of species in laboratory use. Methods A 30-μm thin polymer sheet was implanted subretinally in wild-type (WT) rats. The effects of chronic retinal separation from the RPE were studied using histology and immunohistochemistry. Another approach is applicable to species with avascular retina, such as rabbits, where the photoreceptors and RPE were thermally ablated over large areas, using a high power scanning laser. Results Photoreceptors above the subretinal implant in rats degenerated over time, with 80% of the outer nuclear layer disappearing within a month, and the rest by 3 months. Similar loss was obtained by selective photocoagulation with a scanning laser. Cells in the inner nuclear layer and ganglion cell layer were preserved in both cases. However, there were signs of rewiring and decrease in the size of the bipolar cell terminals in the damaged areas. Conclusions Both methods induce highly reproducible degeneration of photoreceptors over a defined area, with complete preservation of the inner retinal neurons during the 3-month follow-up. They provide a reliable platform for studies of local retinal degeneration and development of therapeutic strategies in a wide variety of species. PMID:26207299

  10. Total disc arthroplasty does not affect the incidence of adjacent segment degeneration in cervical spine: results of 93 patients in three prospective randomized clinical trials.

    PubMed

    Jawahar, Ajay; Cavanaugh, David A; Kerr, Eubulus J; Birdsong, Elisa M; Nunley, Pierce D

    2010-12-01

    than pain score (p<.05). Sixteen percent of TDA patients and 18% ACDF patients developed adjacent segment degeneration and were treated actively (p=.3). Concurrent lumbar DDD significantly increased the risk of adjacent segment degeneration (p=.01). Age, gender, smoking habits, and number of levels at index surgery had no predictive value. Total disc arthroplasty is equivalent to ACDF for providing relief from symptoms in the treatment of one- and two-level DDD of cervical spine. The risk of developing adjacent segment degeneration is equivalent after both procedures but is significantly higher in patients with concurrent DDD in lumbar spine. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Global existence for a degenerate haptotaxis model of cancer invasion

    NASA Astrophysics Data System (ADS)

    Zhigun, Anna; Surulescu, Christina; Uatay, Aydar

    2016-12-01

    We propose and study a strongly coupled PDE-ODE system with tissue-dependent degenerate diffusion and haptotaxis that can serve as a model prototype for cancer cell invasion through the extracellular matrix. We prove the global existence of weak solutions and illustrate the model behavior by numerical simulations for a two-dimensional setting.

  12. Novel human intervertebral disc strain template to quantify regional three-dimensional strains in a population and compare to internal strains predicted by a finite element model.

    PubMed

    Showalter, Brent L; DeLucca, John F; Peloquin, John M; Cortes, Daniel H; Yoder, Jonathon H; Jacobs, Nathan T; Wright, Alexander C; Gee, James C; Vresilovic, Edward J; Elliott, Dawn M

    2016-07-01

    Tissue strain is an important indicator of mechanical function, but is difficult to noninvasively measure in the intervertebral disc. The objective of this study was to generate a disc strain template, a 3D average of disc strain, of a group of human L4-L5 discs loaded in axial compression. To do so, magnetic resonance images of uncompressed discs were used to create an average disc shape. Next, the strain tensors were calculated pixel-wise by using a previously developed registration algorithm. Individual disc strain tensor components were then transformed to the template space and averaged to create the disc strain template. The strain template reduced individual variability while highlighting group trends. For example, higher axial and circumferential strains were present in the lateral and posterolateral regions of the disc, which may lead to annular tears. This quantification of group-level trends in local 3D strain is a significant step forward in the study of disc biomechanics. These trends were compared to a finite element model that had been previously validated against the disc-level mechanical response. Depending on the strain component, 81-99% of the regions within the finite element model had calculated strains within one standard deviation of the template strain results. The template creation technique provides a new measurement technique useful for a wide range of studies, including more complex loading conditions, the effect of disc pathologies and degeneration, damage mechanisms, and design and evaluation of treatments. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1264-1273, 2016. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  13. Mouse models for studies of retinal degeneration and diseases

    PubMed Central

    Chang, Bo

    2013-01-01

    Summary Mouse models, with their well-developed genetics and similarity to human physiology and anatomy, serve as powerful tools with which to investigate the etiology of human retinal degeneration. Mutant mice also provide reproducible, experimental systems for elucidating pathways of normal development and function. Here, I describe the tools used in the discoveries of many retinal degeneration models, including indirect ophthalmoscopy (to look at the fundus appearance), fundus photography and fluorescein angiography (to document the fundus appearance), electroretinography (to check retinal function) as well as the heritability test (for genetic characterization). PMID:23150358

  14. Photochemical-dynamical models of externally FUV irradiated protoplanetary discs

    NASA Astrophysics Data System (ADS)

    Haworth, Thomas J.; Boubert, Douglas; Facchini, Stefano; Bisbas, Thomas G.; Clarke, Cathie J.

    2016-12-01

    There is growing theoretical and observational evidence that protoplanetary disc evolution may be significantly affected by the canonical levels of far-ultraviolet (FUV) radiation found in a star-forming environment, leading to substantial stripping of material from the disc outer edge even in the absence of nearby massive stars. In this paper, we perform the first full radiation hydrodynamic simulations of the flow from the outer rim of protoplanetary discs externally irradiated by such intermediate strength FUV fields, including direct modelling of the photon-dominated region which is required to accurately compute the thermal properties. We find excellent agreement between our models and the semi-analytic models of Facchini et al. (2016) for the profile of the flow itself, as well as the mass-loss rate and location of their `critical radius'. This both validates their results (which differed significantly from prior semi-analytic estimates) and our new numerical method, the latter of which can now be applied to elements of the problem that the semi-analytic approaches are incapable of modelling. We also obtain the composition of the flow, but given the simple geometry of our models we can only hint at some diagnostics for future observations of externally irradiated discs at this stage. We also discuss the potential for these models as benchmarks for future photochemical-dynamical codes.

  15. The noncoding RNA linc-ADAMTS5 cooperates with RREB1 to protect from intervertebral disc degeneration through inhibiting ADAMTS5 expression.

    PubMed

    Wang, Kun; Song, Yu; Liu, Wei; Wu, Xinghuo; Zhang, Yukun; Li, Shuai; Kang, Liang; Tu, Ji; Zhao, Kangcheng; Hua, Wenbin; Yang, Cao

    2017-03-24

    Previous studies have indicated the important roles of ADAMTS5 in intervertebral disc degeneration. However, the mechanisms that regulate ADAMTS5 expression in nuclear pulposus (NP) cells remain largely unknown. Evidence suggests that intergenic transcription may be associated with genes that encode transcriptional regulators. Here, we identified a long intergenic noncoding RNA, linc-ADAMTS5, that was transcribed in the opposite direction of ADAMTS5. In this study, through mining computational algorithm programs, and public available data sets, we identified Ras responsive element binding protein 1 (RREB1) as a crucial transcription factor regulating the expression of ADAMTS5 in NP cells. RNA pull-down, RNA immunoprecipitation, in vitro binding assays, and gain- and loss-of-function studies indicated that a physical interaction between linc-ADAMTS5 and splicing factor proline/glutamine-rich (SFPQ) facilitated the recruitment of RREB1 to binding sites within the ADAMTS5 promoter to induce chromatin remodeling. This resulted in subdued ADAMTS5 levels in cultured NP cells involving histone deacetylases. In clinical NP tissues, linc-ADAMTS5 and RREB1 were correlated negatively with ADAMTS5 expression. Taken together, these results demonstrate that RREB1 cooperates with noncoding RNA linc-ADAMTS5 to inhibit ADAMTS5 expression, thereby affecting degeneration of the extracellular matrix of the intervertebral disc.

  16. From birth to death of protoplanetary discs: modelling their formation, evolution and dispersal

    NASA Astrophysics Data System (ADS)

    Kimura, Shigeo S.; Kunitomo, Masanobu; Takahashi, Sanemichi Z.

    2016-09-01

    The formation, evolution and dispersal processes of protoplanetary discs are investigated and the disc lifetime is estimated. The gravitational collapse of a pre-stellar core forms both a central star and a protoplanetary disc. The central star grows by accretion from the disc and irradiation by the central star heats up the disc and generates a thermal wind, which results in the disc's dispersal. Using the one-dimensional diffusion equation, we calculate the evolution of protoplanetary discs numerically. To calculate the disc evolution from formation to dispersal, we add source and sink terms that represent gas accretion from pre-stellar cores and photoevaporation, respectively. We find that the disc lifetimes of typical pre-stellar cores are around 2-4 million years (Myr). A pre-stellar core with high angular momentum forms a larger disc with a long lifetime, while a disc around an X-ray-luminous star has a short lifetime. Integrating disc lifetimes under various masses and angular velocities of pre-stellar cores and X-ray luminosities of young stellar objects, we obtain the disc fraction at a given stellar age and mean lifetime of the disc. Our model indicates that the mean lifetime of a protoplanetary disc is 3.7 Myr, which is consistent with the observational estimate from young stellar clusters. We also find that the dispersion of X-ray luminosity is needed to reproduce the observed disc fraction.

  17. The presence of local mesenchymal progenitor cells in human degenerated intervertebral discs and possibilities to influence these in vitro: a descriptive study in humans.

    PubMed

    Brisby, Helena; Papadimitriou, Nikolaos; Brantsing, Camilla; Bergh, Peter; Lindahl, Anders; Barreto Henriksson, Helena

    2013-03-01

    Low back pain is common and degenerated discs (DDs) are believed to be a major cause. In non-degenerated intervertebral discs (IVDs) presence of stem/progenitor cells was recently reported in different mammals (rabbit, rat, pig). Understanding processes of disc degeneration and regenerative mechanisms within DDs is important. The aim of the study was to examine the presence of local stem/progenitor cells in human DDs and if these cell populations could respond to paracrine stimulation in vitro. Tissue biopsies from the IVD region (L3-S1) were collected from 15 patients, age 34-69 years, undergoing surgery (spinal fusion) and mesenchymal stem cells (MSCs) (iliac crest) from 2 donors. Non-DD cells were collected from 1 donor (scoliosis) and chordoma tissue was obtained from (positive control, stem cell markers) 2 donors. The IVD biopsies were investigated for gene and protein expression of: OCT3/4, CD105, CD90, STRO-1, and NOTCH1. DD cell cultures (pellet mass) were performed with conditioned media from MSCs and non-degenerated IVD cells. Pellets were investigated after 7, 14, 28 days for the same stem cell markers as above. Gene expression of OCT3/4 and STRO-1 was detected in 13/15 patient samples, CD105 in 14/15 samples, and CD90 and NOTCH1 were detected 15/15 samples. Immunohistochemistry analysis supported findings on the protein level, in cells sparsely distributed in DDs tissues. DDs cell cultures displayed more undifferentiated appearance with increased expression of CD105, CD90, STRO-1, OCT3/4, NOTCH1, and JAGGED1, which was observed when cultured in conditioned cell culture media from MSCs compared to cell cultures cultured with conditioned media from non-DD cells. Expression of OCT3/4 (multipotency marker) and NOTCH1 (regulator of cell fate), MSC-markers, CD105, CD90, and STRO-1, indicate that primitive cell populations are present within DDs. Furthermore, the possibility to influence cells from DDs by paracrine signaling /soluble factors from MSCs and from

  18. Collisional modelling of the debris disc around HIP 17439

    NASA Astrophysics Data System (ADS)

    Schüppler, Ch.; Löhne, T.; Krivov, A. V.; Ertel, S.; Marshall, J. P.; Eiroa, C.

    2014-07-01

    We present an analysis of the debris disc around the nearby K2 V star HIP 17439. In the context of the Herschel DUNES key programme, the disc was observed and spatially resolved in the far-IR with the Herschel PACS and SPIRE instruments. In a previous study, we assumed that the size and radial distribution of the circumstellar dust are independent power laws. There, several scenarios capable of explaining the observations were suggested after exploring a very broad range of possible model parameters. In this paper, we perform a follow-up in-depth collisional modelling of these scenarios to further distinguish between them. In our models we consider collisions, direct radiation pressure, and drag forces, which are the actual physical processes operating in debris discs. We find that all scenarios discussed in the first paper are physically reasonable and can reproduce the observed spectral energy distribution along with the PACS surface brightness profiles reasonably well. In one model, the dust is produced beyond 120 au in a narrow planetesimal belt and is transported inwards by Poynting-Robertson and stellar wind drag. Good agreement with the observed radial profiles would require stellar winds by about an order of magnitude stronger than the solar value, which is not confirmed - although not ruled out - by observations. Another model consists of two spatially separated planetesimal belts, a warm inner and a cold outer one. This scenario would probably imply the presence of planets clearing the gap between the two components. Finally, we show qualitatively that the observations can be explained by assuming the dust is produced in a single, but broad planetesimal disc with a surface density of solids rising outwards, as expected for an extended disc that experiences a natural inside-out collisional depletion. Prospects of distinguishing between the competing scenarios by future observations are discussed.

  19. Development and Translation of a Tissue- Engineered Disc in a Preclinical Rodent Model

    DTIC Science & Technology

    2011-10-01

    exposure for stem cells cultured in an engineered nucleus pulposus-like hyaluronan hydrogel. We have developed and validated a minimally invasive...a hyaluronic acid hydrogel seeded with adult stem cells that can be used to replace the degenerate native disc. Proposed Aim 1: Create a...mesenchymal stem cell (MSC) seeded 3D structural TEC disc from concentric AF constructs surrounding an engineered nucleus pulposus (NP) composed of a

  20. Radiative transfer modelling of parsec-scale dusty warped discs

    NASA Astrophysics Data System (ADS)

    Jud, H.; Schartmann, M.; Mould, J.; Burtscher, L.; Tristram, K. R. W.

    2017-02-01

    Warped discs have been found on (sub-)parsec scale in some nearby Seyfert nuclei, identified by their maser emission. Using dust radiative transfer simulations, we explore their observational signatures in the infrared in order to find out whether they can partly replace the molecular torus. Strong variations of the brightness distributions are found, depending on the orientation of the warp with respect to the line of sight. Whereas images at short wavelengths typically show a disc-like and a point source component, the warp itself only becomes visible at far-infrared wavelengths. A similar variety is visible in the shapes of the spectral energy distributions. Especially for close to edge-on views, the models show silicate feature strengths ranging from deep absorption to strong emission for variations of the lines of sight towards the warp. To test the applicability of our model, we use the case of the Circinus galaxy, where infrared interferometry has revealed a highly elongated emission component matching a warped maser disc in orientation and size. Our model is for the first time able to present a physical explanation for the observed dust morphology as coming from the active galactic nuclei heated dust. As opposed to available torus models, a warped disc morphology produces a variety of silicate feature shapes for grazing lines of sight, close to an edge-on view. This could be an attractive alternative to a claimed change of the dust composition for the case of the nearby Seyfert 2 galaxy NGC 1068, which harbours a warped maser disc as well.

  1. Frontotemporal degeneration, the next therapeutic frontier: molecules and animal models for frontotemporal degeneration drug development.

    PubMed

    Boxer, Adam L; Gold, Michael; Huey, Edward; Gao, Fen-Biao; Burton, Edward A; Chow, Tiffany; Kao, Aimee; Leavitt, Blair R; Lamb, Bruce; Grether, Megan; Knopman, David; Cairns, Nigel J; Mackenzie, Ian R; Mitic, Laura; Roberson, Erik D; Van Kammen, Daniel; Cantillon, Marc; Zahs, Kathleen; Salloway, Stephen; Morris, John; Tong, Gary; Feldman, Howard; Fillit, Howard; Dickinson, Susan; Khachaturian, Zaven; Sutherland, Margaret; Farese, Robert; Miller, Bruce L; Cummings, Jeffrey

    2013-03-01

    Frontotemporal degeneration (FTD) is a common cause of dementia for which there are currently no approved therapies. Over the past decade, there has been an explosion of knowledge about the biology and clinical features of FTD that has identified a number of promising therapeutic targets as well as animal models in which to develop drugs. The close association of some forms of FTD with neuropathological accumulation of tau protein or increased neuroinflammation due to progranulin protein deficiency suggests that a drug's success in treating FTD may predict efficacy in more common diseases such as Alzheimer's disease. A variety of regulatory incentives, clinical features of FTD such as rapid disease progression, and relatively pure molecular pathology suggest that there are advantages to developing drugs for FTD as compared with other more common neurodegenerative diseases such as Alzheimer's disease. In March 2011, the Frontotemporal Degeneration Treatment Study Group sponsored a conference entitled "FTD, the Next Therapeutic Frontier," which focused on preclinical aspects of FTD drug development. The goal of the meeting was to promote collaborations between academic researchers and biotechnology and pharmaceutical researchers to accelerate the development of new treatments for FTD. Here we report the key findings from the conference, including the rationale for FTD drug development; epidemiological, genetic, and neuropathological features of FTD; FTD animal models and how best to use them; and examples of successful drug development collaborations in other neurodegenerative diseases. Copyright © 2013 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  2. Short-segment fixation without fusion for thoracolumbar burst fractures with neurological deficit can preserve thoracolumbar motion without resulting in post-traumatic disc degeneration: a 10-year follow-up study.

    PubMed

    Toyone, Tomoaki; Ozawa, Tomoyuki; Inada, Kunimasa; Shirahata, Toshiyuki; Shiboi, Ryutaro; Watanabe, Atsuya; Matsuki, Keisuke; Hasue, Fumio; Fujiyoshi, Takayuki; Aoki, Yasuchika; Inoue, Gen; Orita, Sumihisa; Ohtori, Seiji; Wada, Yuichi; Tanaka, Tadashi; Takahashi, Kazuhisa

    2013-08-01

    Prospective consecutive series. To evaluate the post-traumatic disc degeneration and range of motion 10 years after short-segment fixation without fusion for thoracolumbar burst fractures with neurological deficit. Early clinical results of short-segment fixation without fusion for thoracolumbar burst fractures were satisfactory. However, the long-term results have not been reported, and post-traumatic disc degeneration and preservation of thoracolumbar motion have not been elucidated. Twelve patients who had thoracolumbar burst fractures and associated incomplete neurological deficit, operatively treated within 4 days of admission and had their implants removed within 1 year, were prospectively followed for at least 10 years. Following indirect reduction and pedicle screw fixation, transpedicular intracorporeal hydroxyapatite grafting to the fractured vertebrae was performed. Sagittal alignment was improved from a mean preoperative kyphosis of 17° to -2° (lordosis) by operation, but was found to have slightly deteriorated to 2° at the final follow-up observation. With respect to back pain, 8 patients did not report back pain. Three reported occasional minimal pain, and 1 reported moderate pain. None reported severe pain or needed daily dosages of analgesics.Regarding disc degeneration, the shape of the disc adjacent to the fractured vertebra had not changed from the preoperative to the 10-year postoperative magnetic resonance image (MRI). Although signal intensity of the disc had decreased by 1 grade from the preoperative to the 2-year postoperative MRI, the intensity had not changed from the 2-year postoperative MRI to the 10-year postoperative MRI. At the 10-year follow-up, flexion-extension radiographs revealed that a mean range of motion at the disc adjacent to the fractured vertebra was 12º (range; 5-19). This unprecedented 10-year follow-up study demonstrated that posterior indirect reduction, transpedicular hydroxyapatite grafting, and pedicle screw

  3. Selective rod degeneration and partial cone inactivation characterize an iodoacetic acid model of Swine retinal degeneration.

    PubMed

    Wang, Wei; Fernandez de Castro, Juan; Vukmanic, Eric; Zhou, Liang; Emery, Douglas; Demarco, Paul J; Kaplan, Henry J; Dean, Douglas C

    2011-10-07

    PURPOSE. Transgenic pigs carrying a mutant human rhodopsin transgene have been developed as a large animal model of retinitis pigmentosa (RP). This model displays some key features of human RP, but the time course of disease progression makes this model costly, time consuming, and difficult to study because of the size of the animals at end-stage disease. Here, the authors evaluate an iodoacetic acid (IAA) model of photoreceptor degeneration in the pig as an alternative model that shares features of the transgenic pig and human RP. METHODS. IAA blocks glycolysis, thereby inhibiting photoreceptor function. The effect of the intravenous injection of IAA on swine rod and cone photoreceptor viability and morphology was followed by histologic evaluation of different regions of the retina using hematoxylin and eosin and immunostaining. Rod and cone function was analyzed by full-field electroretinography and multifocal electroretinography. RESULTS. IAA led to specific loss of rods in a central-to-peripheral retinal gradient. Although cones were resistant, they showed shortened outer segments, loss of bipolar cell synaptic connections, and a diminished flicker ERG, hallmarks of transition to cone dysfunction in RP patients. CONCLUSIONS. IAA provides an alternative rod-dominant model of retinal damage that shares a surprising number of features with the pig transgenic model of RP and with human RP. This IAA model is cost-effective and rapid, ensuring that the size of the animals does not become prohibitive for end-stage evaluation or therapeutic intervention.

  4. On degenerate models of cosmic inflation

    SciTech Connect

    Gwyn, Rhiannon; Palma, Gonzalo A.; Sakellariadou, Mairi; Sypsas, Spyros E-mail: gpalmaquilod@ing.uchile.cl E-mail: s.sypsas@apctp.org

    2014-10-01

    In this article we discuss the role of current and future CMB measurements in pinning down the model of inflation responsible for the generation of primordial curvature perturbations. By considering a parameterization of the effective field theory of inflation with a modified dispersion relation arising from heavy fields, we derive the dependence of cosmological observables on the scale of heavy physics Λ{sub UV}. Specifically, we show how the f{sub NL} non-linearity parameters are related to the phase velocity of curvature perturbations at horizon exit, which is parameterized by Λ{sub UV}. BICEP2 and PLANCK findings are shown to be consistent with a value Λ{sub UV} ∼ Λ{sub GUT}. However, we find a degeneracy in the parameter space of inflationary models that can only be resolved with a detailed knowledge of the shape of the non-Gaussian bispectrum.

  5. A 20-year-old female with Hirayama disease complicated with dysplasia of the cervical vertebrae and degeneration of intervertebral discs

    PubMed Central

    Hashimoto, Masaya; Yoshioka, Masayuki; Sakimoto, Yoshihiro; Suzuki, Masahiko

    2012-01-01

    A 20-year-old female patient was presented with a 1-year history of progressive weakness of the left hand. Examination on admission showed atrophy of the muscles of the left forearm, cold paralysis and minipolymyoclonus. MR images of the cervical cord showed anterior transfer of the cervical cord on anterior flexion and cervical cord compression at the site of cervical kyphosis, confirming the diagnosis of Hirayama disease. Many features of the present case are unusual: the patient is a female (who are rarely afflicted by this disease), with cervical kyphosis and a history of exercise involving cervical vertebral loading, suggesting a potential involvement of the latter two factors in the disease onset. The findings suggest that cervical vertebral dysplasia and intervertebral disc degeneration may influence cervical kyphosis, and be involved in the onset of Hirayama disease. PMID:23144342

  6. From Disc Wind Models to Observations of TTauri Microjets

    NASA Astrophysics Data System (ADS)

    Ferreira, Jonathan; Casse, Fabien; Garcia, Paulo; Darren, O'brien; Sylvie, Cabrit; Catherine, Dougados; Pesenti, Nicolas; Luc, Binette

    Two decades after their discovery jets from accreting young stars still represent a major challenge for theorists. Several theoretical scenarii have been proposed but only models involving large scale magnetic fields have proved capable of producing self-collimated jets. However the launching region remains unknown: is it the star the surrounding accretion disc or their interaction zone? Progresses in high angular resolution offer now the opportunity to test the various proposed models. I will first review the results on magnetized disc winds based on the only MHD model describing self-consistently these accretion-ejection structures. Then I will show how the thermal and ionization states of the outflowing matter can be consistently computed once the dominant heating source has been chosen (ambipolar diffusion alfven wave damping or some local mechanical heating). A set of observational predictions (emission maps line fluxes/ratios and line profiles) for selected optical forbidden lines can then be calculated. As an illustration I will compare these predictions with new sub-arcsecond spectroimaging observations of the DG Tau and RW Aur jets and discuss the constraints they set on disc winds in TTauri stars.

  7. Modeling Jupiter's current disc - Pioneer 10 outbound

    NASA Technical Reports Server (NTRS)

    Jones, D. E.; Melville, J. G., II; Blake, M. L.

    1980-01-01

    A model of the magnetic field of the Jovian current disk is presented. The model uses Euler functions and the Biot-Savart law applied to a series of concentric, but not necessarily coplanar current rings. It was found that the best fit to the Pioneer 10 outbound perturbation magnetic field data is obtained if the current disk is twisted, and also bent to tend toward parallelism with the Jovigraphic equator. The inner and outer radii of the disk appear to be about 7 and 150 Jovian radii, respectively; because of the observed current disk penetrations, the bent disk also requires a deformation in the form of a bump or wrinkle whose axis tends to exhibit spiraling. Modeling of the azimuthal field shows that it is due to a thin radial current sheet, but it may actually be due in large part to penetration of a tail current sheet as suggested by Voyager observations.

  8. Collisional modelling of the AU Microscopii debris disc

    NASA Astrophysics Data System (ADS)

    Schüppler, Ch.; Löhne, T.; Krivov, A. V.; Ertel, S.; Marshall, J. P.; Wolf, S.; Wyatt, M. C.; Augereau, J.-C.; Metchev, S. A.

    2015-09-01

    AU Microscopii's debris disc is one of the most famous and best-studied debris discs and one of only two resolved debris discs around M stars. We perform in-depth collisional modelling of the AU Mic disc including stellar radiative and corpuscular forces (stellar winds), aiming at a comprehensive understanding of the dust production and the dust and planetesimal dynamics in the system. Our models are compared to a suite of observational data for thermal and scattered light emission, ranging from the ALMA radial surface brightness profile at 1.3 mm to spatially resolved polarisation measurements in the visible. Most of the data are shown to be reproduced with dust production in a belt of planetesimals with an outer edge at around 40 au and subsequent inward transport of dust by stellar winds. A low dynamical excitation of the planetesimals with eccentricities up to 0.03 is preferred. The radial width of the planetesimal belt cannot be constrained tightly. Belts that are 5 au and 17 au wide, as well as a broad 44 au-wide belt, are consistent with observations. All models show surface density profiles that increase with distance from the star up to ≈40 au, as inferred from observations. The best model is achieved by assuming a stellar mass loss rate that exceeds the solar one by a factor of 50. The models reproduce the spectral energy distribution and the shape of the ALMA radial profile well, but deviate from the scattered light observations more strongly. The observations show a bluer disc colour and a lower degree of polarisation for projected distances <40 au than predicted by the models. These deviations may be reduced by taking irregularly shaped dust grains which have scattering properties different from the Mie spheres used in this work. From tests with a handful of selected dust materials, we favour mixtures of silicate, carbon, and ice of moderate porosity. We also address the origin of the unresolved central excess emission detected by ALMA and show that

  9. Degeneration of the Y chromosome in evolutionary aging models

    NASA Astrophysics Data System (ADS)

    Lobo, M. P.; Onody, R. N.

    2005-06-01

    The Y chromosomes are genetically degenerated and do not recombine with their matching partners X. Recombination of XX pairs is pointed out as the key factor for the Y chromosome degeneration. However, there is an additional evolutionary force driving sex-chromosomes evolution. Here we show this mechanism by means of two different evolutionary models, in which sex chromosomes with non-recombining XX and XY pairs of chromosomes is considered. Our results show three curious effects. First, we observed that even when both XX and XY pairs of chromosomes do not recombine, the Y chromosomes still degenerate. Second, the accumulation of mutations on Y chromosomes followed a completely different pattern then those accumulated on X chromosomes. And third, the models may differ with respect to sexual proportion. These findings suggest that a more primeval mechanism rules the evolution of Y chromosomes due exclusively to the sex-chromosomes asymmetry itself, i.e., the fact that Y chromosomes never experience female bodies. Over aeons, natural selection favored X chromosomes spontaneously, even if at the very beginning of evolution, both XX and XY pairs of chromosomes did not recombine.

  10. Dysregulated miR-127-5p contributes to type II collagen degradation by targeting matrix metalloproteinase-13 in human intervertebral disc degeneration.

    PubMed

    Hua, Wen-Bin; Wu, Xing-Huo; Zhang, Yu-Kun; Song, Yu; Tu, Ji; Kang, Liang; Zhao, Kang-Cheng; Li, Shuai; Wang, Kun; Liu, Wei; Shao, Zeng-Wu; Yang, Shu-Hua; Yang, Cao

    2017-08-01

    Intervertebral disc degeneration (IDD) is a chronic disease associated with the degradation of extracellular matrix (ECM). Matrix metalloproteinase (MMP)-13 is a major enzyme that mediates the degradation of ECM components. MMP-13 has been predicted to be a potential target of miR-127-5p. However, the exact function of miR-127-5p in IDD is still unclear. We designed this study to evaluate the correlation between miR-127-5p level and the degeneration of human intervertebral discs and explore the potential mechanisms. miR-127-5p levels and MMP-13 mRNA levels were detected by quantitative real-time polymerase chain reaction (qPCR). To determine whether MMP-13 is a target of miR-127-5p, dual luciferase reporter assays were performed. miR-127-5p mimic and miR-127-5p inhibitor were used to overexpress or downregulate miR-127-5p expression in human NP cells, respectively. Small interfering RNA (siRNA) was used to knock down MMP-13 expression in human NP cells. Type II collagen expression in human NP cells was detected by qPCR, western blotting, and immunofluorescence staining. We confirmed that miR-127-5p was significantly downregulated in nucleus pulposus (NP) tissue of degenerative discs and its expression was inversely correlated with MMP-13 mRNA levels. We reveal that MMP-13 may act as a target of miR-127-5p. Expression of miR-127-5p was inversely correlated with type II collagen expression in human NP cells. Moreover, suppression of MMP-13 expression by siRNA blocked downstream signaling and increased type II collagen expression. Dysregulated miR-127-5p contributed to the degradation of type II collagen by targeting MMP-13 in human IDD. Our findings highlight that miR-127-5p may serve as a new therapeutic target in IDD. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  11. Disc positions and condylar changes induced by different stretching forces in the model for anterior disc displacement of temporomandibular joint.

    PubMed

    Li, Hui; Cai, Xieyi; Wang, Shaoyi; Yang, Chi; Song, Hao; Huang, Linjian

    2014-11-01

    The aim of this study was to compare the disc positions and condylar changes induced by different stretching forces in the modified animal model for anterior disc displacement (ADD) of the temporomandibular joint. In the experimental group, 30 rabbits were equally divided into 3 subgroups and underwent surgical ADD via different stretching forces: group A with 0.5 N, group B with 1 N, and group C with 2 N. In the sham group, 6 rabbits underwent the same surgery without the disc being pulled anteriorly. The diagnosis of ADD was made when the anterior band of the disc was located anteriorly to the articular eminence. Histologic and radiographic changes of the condyles were observed under light microscopy and micro-computed tomography scanning 1 week after surgery. The success rates of ADD were both 100% in groups B and C and 70% in group A. The correlations between the stretching force and severity of ADD, the stretching force and severity of cartilage changes, and the severity of ADD and cartilage changes were statistically significant (P < 0.01). The most advanced ADD and severest condylar changes were induced in group C. Condylar remodeling and scleroses were found in micro-computed tomography scans. The rabbit model for ADD has been successfully established in this study, which is feasible and minimally invasive. The stretching force of at least 1 N could induce the disc displaced successfully. Larger stretching force would induce severer ADD and condylar degenerative changes.

  12. Modelling creep behaviour of the human intervertebral disc.

    PubMed

    van der Veen, Albert J; Bisschop, Arno; Mullender, Margriet G; van Dieën, Jaap H

    2013-08-09

    The mechanical behaviour of an intervertebral disc is time dependent. In literature different constitutive equations have been used to describe creep. It is unsure whether these different approaches yield valid predictions. In this study, we compared the validity of different equations for the prediction of creep behaviour. To this end, human thoracic discs were preloaded at 0.1 MPa for 12h, compressed (0.8 MPa) for 24h and finally unloaded (0.1 MPa) for 24h. A Kohlrausch-Williams-Watts (KWW) model and a Double-Voight (DV) model were fitted to the creep data. Model parameters were calculated for test durations of 4, 8, 12, 16, 20 and 24h. Both models described the measured data well, but parameters were highly sensitive to test duration. The estimated time constant varied with test duration from 3.6 to 17h. When extrapolating beyond test duration, the DV model under-estimated and the KWW model over-estimated creep. The 24h experiment was still too short for an accurate determination of the parameters. Therefore, parameters obtained in this paper can be used to describe normal behaviour, but are not suitable for extrapolation beyond the test duration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Hyper-elastic modelling of intervertebral disc polyurethane implant.

    PubMed

    Pawlikowski, Marek; Skalski, Konstanty; Sowiński, Tomasz

    2013-01-01

    Artificial materials including various kinds of polymers like polyurethanes are more and more widely used in different branches of science and also in biomedical engineering. The paper presents the process of creating a constitutive equation for a polyurethane nanocomposite which is considered to be hyper-elastic. The constitutive modelling was conducted within the range of application of the material as one of the components of lumbar intervertebral disc prosthesis. In the paper, the biomechanics of the lumbar spine and the most frequently applied intervertebral disc prostheses are described. Also a polyurethane nanocomposite as a new material to be applied in prostheses is presented. The way of formulating a constitutive equation by means of mathematical formulae is described. Four various hyper-elastic potential functions are considered, i.e., Ogden, Neo-Hookean, Yeoh and Mooney-Rivlin. On the basis of monotonic compression tests the best hyper-elastic model for the material considered was chosen and hyper-elastic constants were calibrated. Finally, the constitutive model was validated on the basis of FE analysis. The paper ends with a conclusion and presentation of further plans of research directed towards the development of a constitutive equation and its application in computer simulations by means of the finite element method.

  14. Radiative neutrino mass model with degenerate right-handed neutrinos

    NASA Astrophysics Data System (ADS)

    Kashiwase, Shoichi; Suematsu, Daijiro

    2016-03-01

    The radiative neutrino mass model can relate neutrino masses and dark matter at a TeV scale. If we apply this model to thermal leptogenesis, we need to consider resonant leptogenesis at that scale. It requires both finely degenerate masses for the right-handed neutrinos and a tiny neutrino Yukawa coupling. We propose an extension of the model with a U(1) gauge symmetry, in which these conditions are shown to be simultaneously realized through a TeV scale symmetry breaking. Moreover, this extension can bring about a small quartic scalar coupling between the Higgs doublet scalar and an inert doublet scalar which characterizes the radiative neutrino mass generation. It also is the origin of the Z_2 symmetry which guarantees the stability of dark matter. Several assumptions which are independently supposed in the original model are closely connected through this extension.

  15. Spinal traction promotes molecular transportation in a simulated degenerative intervertebral disc model.

    PubMed

    Kuo, Ya-Wen; Hsu, Yu-Chun; Chuang, I-Ting; Chao, Pen-Hsiu Grace; Wang, Jaw-Lin

    2014-04-20

    Biomechanical experiment using an in situ porcine model. To find the effect of traction treatment on annulus microstructure, molecular convection, and cell viability of degraded discs. Spinal traction is a conservative treatment for disc disorders. The recognized biomechanical benefits include disc height recovery, foramen enlargement, and intradiscal pressure reduction. However, the influence of traction treatment on annulus microstructure, molecular transportation, and cell viability of degraded discs has not been fully investigated. A total of 48 thoracic discs were dissected from 8 porcine spines (140 kg, 6-month old) within 4 hours after killing them and then divided into 3 groups: intact, degraded without traction, and degraded with traction. Each disc was incubated in a whole-organ culture system and subjected to diurnal loadings for 7 days. Except for the intact group, discs were degraded with 0.5 mL of trypsin on day 1 and a 5-hour fatigue loading on day 2. From day 4 to day 6, half of the degraded discs received a 30-minute traction treatment per day (traction force: 20 kg; loading: unloading = 30 s: 10 s). By the end of the incubation, the discs were inspected for disc height loss, annulus microstructure, molecular (fluorescein sodium) intensity, and cell viability. Collagen fibers were crimped and delaminated, whereas the pores were occluded in the annulus fibrosus of the degraded discs. Molecular transportation and cell viability of the discs decreased after matrix degradation. With traction treatment, straightened collagen fibers increased within the degraded annulus fibrosus, and the annulus pores were less occluded. Both molecular transportation and cell viability increased, but not to the intact level. Traction treatment is effective in enhancing nutrition supply and promoting disc cell proliferation of the degraded discs. N/A.

  16. Torus models of the outer disc of the Milky Way using LAMOST survey data

    NASA Astrophysics Data System (ADS)

    Wang, Qiao; Wang, Yougang; Liu, Chao; Mao, Shude; Long, R. J.

    2017-09-01

    With a sample of 48 161 K giant stars selected from the LAMOST DR 2 catalogue, we construct torus models in a large volume extending, for the first time, from the solar vicinity to a Galactocentric distance of ∼20 kpc, reaching the outskirts of the Galactic disc. We show that the kinematics of the K giant stars match conventional models, e.g. as created by Binney in 2012, in the Solar vicinity. However such two-disc models fail if they are extended to the outer regions, even if an additional disc component is utilized. If we loosen constraints in Sun's vicinity, we find that an effective thick disc model could explain the anticentre of the MW. The Large Area Multi-Object Spectroscopic Telescope data imply that the sizes of the Galactic discs are much larger, and that the outer disc is much thicker, than previously thought, or alternatively that the outer structure is not a conventional disc at all. However, the velocity dispersion σ0z of the kinematically thick disc in the best-fitting model is about 80 km s-1 and has a scale parameter Rσ for an exponential distribution function of ∼19 kpc. Such a height σ0z is strongly rejected by current measurements in the solar neighbourhood, and thus a model beyond quasi-thermal, two or three thin or thick discs is required.

  17. The life cycles of Be viscous decretion discs: time-dependent modelling of infrared continuum observations

    NASA Astrophysics Data System (ADS)

    Vieira, R. G.; Carciofi, A. C.; Bjorkman, J. E.; Rivinius, Th.; Baade, D.; Rímulo, L. R.

    2017-01-01

    We apply the viscous decretion disc (VDD) model to interpret the infrared disc continuum emission of 80 Be stars observed in different epochs. In this way, we determined 169 specific disc structures, namely their density scale, ρ0, and exponent, n. We found that the n values range mainly between 1.5 and 3.5, and ρ0 varies between 10-12 and 10-10 g cm-3, with a peak close to the lower value. Our large sample also allowed us to firmly establish that the discs around early-type stars are denser than in late-type stars. Additionally, we estimated the disc mass decretion rates and found that they range between 10-12 and 10-9 M⊙ yr-1. These values are compatible with recent stellar evolution models of fast-rotating stars. One of the main findings of this work is a correlation between the ρ0 and n values. In order to find out whether these relations can be traced back to the evolution of discs or have some other origin, we used the VDD model to calculate temporal sequences under different assumptions for the time profile of the disc mass injection. The results support the hypothesis that the observed distribution of disc properties is due to a common evolutionary path. In particular, our results suggest that the time-scale for disc growth, during which the disc is being actively fed by mass injection episodes, is shorter than the time-scale for disc dissipation, when the disc is no longer fed by the star and dissipates as a result of the viscous diffusion of the disc material.

  18. Development and Translation of a Tissue-Engineered Disc in a Preclinical Rodent Model

    DTIC Science & Technology

    2011-10-01

    We have shown that a short period of exposure to transforming at a high dose is equal to or better than long term exposure for stem cells cultured...seeded with adult stem cells that can be used to replace the degenerate native disc. Proposed Aim 1: Create a mesenchymal stem cell (MSC) seeded 3D...establishes the NP and AF cell phenotype. Our focus here was on the formation and maturation of the mesenchymal stem cell (MSC) based nucleus pulposus (NP

  19. Clinical and radiological outcome of anterior–posterior fusion versus transforaminal lumbar interbody fusion for symptomatic disc degeneration: a retrospective comparative study of 133 patients

    PubMed Central

    Schwender, James D.; Safriel, Yair; Gilbert, Thomas J.; Mehbod, Amir A.; Denis, Francis; Transfeldt, Ensor E.; Wroblewski, Jill M.

    2009-01-01

    Abundant data are available for direct anterior/posterior spine fusion (APF) and some for transforaminal lumbar interbody fusion (TLIF), but only few studies from one institution compares the two techniques. One-hundred and thirty-three patients were retrospectively analyzed, 68 having APF and 65 having TLIF. All patients had symptomatic disc degeneration of the lumbar spine. Only those with one or two-level surgeries were included. Clinical chart and radiologic reviews were done, fusion solidity assessed, and functional outcomes determined by pre- and postoperative SF-36 and postoperative Oswestry Disability Index (ODI), and a satisfaction questionnaire. The minimum follow-up was 24 months. The mean operating room time and hospital length of stay were less in the TLIF group. The blood loss was slightly less in the TLIF group (409 vs. 480 cc.). Intra-operative complications were higher in the APF group, mostly due to vein lacerations in the anterior retroperitoneal approach. Postoperative complications were higher in the TLIF group due to graft material extruding against the nerve root or wound drainage. The pseudarthrosis rate was statistically equal (APF 17.6% and TLIF 23.1%) and was higher than most published reports. Significant improvements were noted in both groups for the SF-36 questionnaires. The mean ODI scores at follow-up were 33.5 for the APF and 39.5 for the TLIF group. The patient satisfaction rate was equal for the two groups. PMID:19125304

  20. Diagram theory for the twofold-degenerate Anderson impurity model

    NASA Astrophysics Data System (ADS)

    Moskalenko, V. A.; Dohotaru, L. A.; Digor, D. F.; Cebotari, I. D.

    2014-02-01

    We develop a diagram technique for investigating the twofold-degenerate Anderson impurity model in the normal state with the strong electronic correlations of d electrons of the impurity ion taken into account. We discuss the properties of the Slater-Kanamori model of d electrons. After finding the eigenfunctions and eigenvalues of all 16 local states, we determine the local one-particle propagator. We construct the perturbation theory around the atomic limit of the impurity ion and obtain a Dyson-type equation establishing the relation between the impurity electron propagator and the normal correlation function. As a result of summing infinite series of ladder diagrams, we obtain an approximation for the correlation function.

  1. Design and fabrication of 3D-printed anatomically shaped lumbar cage for intervertebral disc (IVD) degeneration treatment.

    PubMed

    Serra, T; Capelli, C; Toumpaniari, R; Orriss, I R; Leong, J J H; Dalgarno, K; Kalaskar, D M

    2016-07-19

    Spinal fusion is the gold standard surgical procedure for degenerative spinal conditions when conservative therapies have been unsuccessful in rehabilitation of patients. Novel strategies are required to improve biocompatibility and osseointegration of traditionally used materials for lumbar cages. Furthermore, new design and technologies are needed to bridge the gap due to the shortage of optimal implant sizes to fill the intervertebral disc defect. Within this context, additive manufacturing technology presents an excellent opportunity to fabricate ergonomic shape medical implants. The goal of this study is to design and manufacture a 3D-printed lumbar cage for lumbar interbody fusion. Optimisations of the proposed implant design and its printing parameters were achieved via in silico analysis. The final construct was characterised via scanning electron microscopy, contact angle, x-ray micro computed tomography (μCT), atomic force microscopy, and compressive test. Preliminary in vitro cell culture tests such as morphological assessment and metabolic activities were performed to access biocompatibility of 3D-printed constructs. Results of in silico analysis provided a useful platform to test preliminary cage design and to find an optimal value of filling density for 3D printing process. Surface characterisation confirmed a uniform coating of nHAp with nanoscale topography. Mechanical evaluation showed mechanical properties of final cage design similar to that of trabecular bone. Preliminary cell culture results showed promising results in terms of cell growth and activity confirming biocompatibility of constructs. Thus for the first time, design optimisation based on computational and experimental analysis combined with the 3D-printing technique for intervertebral fusion cage has been reported in a single study. 3D-printing is a promising technique for medical applications and this study paves the way for future development of customised implants in spinal

  2. Building disc structure and galaxy properties through angular momentum: the DARK SAGE semi-analytic model

    NASA Astrophysics Data System (ADS)

    Stevens, Adam R. H.; Croton, Darren J.; Mutch, Simon J.

    2016-09-01

    We present the new semi-analytic model of galaxy evolution, DARK SAGE, a heavily modified version of the publicly available SAGE code. The model is designed for detailed evolution of galactic discs. We evolve discs in a series of annuli with fixed specific angular momentum, which allows us to make predictions for the radial and angular-momentum structure of galaxies. Most physical processes, including all channels of star formation and associated feedback, are performed in these annuli. We present the surface density profiles of our model spiral galaxies, both as a function of radius and specific angular momentum, and find that the discs naturally build a pseudo-bulge-like component. Our main results are focused on predictions relating to the integrated mass-specific angular momentum relation of stellar discs. The model produces a distinct sequence between these properties in remarkable agreement with recent observational literature. We investigate the impact Toomre disc instabilities have on shaping this sequence and find they are crucial for regulating both the mass and spin of discs. Without instabilities, high-mass discs would be systematically deficient in specific angular momentum by a factor of ˜2.5, with increased scatter. Instabilities also appear to drive the direction in which the mass-spin sequence of spiral galaxy discs evolves. With them, we find galaxies of fixed mass have higher specific angular momentum at later epochs.

  3. Cellular models and therapies for age-related macular degeneration

    PubMed Central

    Forest, David L.; Johnson, Lincoln V.; Clegg, Dennis O.

    2015-01-01

    ABSTRACT Age-related macular degeneration (AMD) is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE) cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD). A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease. PMID:26035859

  4. A Simple ``Sticky Disc'' Model for Crystalline and Amorphous Networks

    NASA Astrophysics Data System (ADS)

    Huerta, Adrian; Chubynsky, Nikita; Naumis, Gerardo; Thorpe, Michael

    2005-03-01

    Using Monte Carlo simulations, we study the structural and thermodynamic behavior of a simple one component network forming model made up of ``sticky discs.'' Central and bond bending forces was included, modeling such interactions as a simple square well radial and angular three body term in the potential respectively. The main feature of this model is the ability to form crystalline and amorphous networks upon cooling, similar to that obtained using the so called WWW methodology to describe the network of some vitreous structures [1]. With the ``pebble game'' algorithm [2], we evaluate the number of degrees of freedom and the amount of stress in both the amorphous and crystalline structures. We discuss the connection between the configurational entropy (associated with the topology) and the degrees of freedom. Other effects such as elasticity of these structures are also discussed. 1. Wooten, F., Winer, K. and Weaire, D., Phys. Rev. Lett., 54 1392- 1395 (1985). 2. Jacobs, D.J. and Thorpe, M.F., Phys. Rev. Lett., 75 4051- 4054 (1995).

  5. Tamoxifen Provides Structural and Functional Rescue in Murine Models of Photoreceptor Degeneration.

    PubMed

    Wang, Xu; Zhao, Lian; Zhang, Yikui; Ma, Wenxin; Gonzalez, Shaimar R; Fan, Jianguo; Kretschmer, Friedrich; Badea, Tudor C; Qian, Hao-Hua; Wong, Wai T

    2017-03-22

    Photoreceptor degeneration is a cause of irreversible vision loss in incurable blinding retinal diseases including retinitis pigmentosa (RP) and atrophic age-related macular degeneration. We found in two separate mouse models of photoreceptor degeneration that tamoxifen, a selective estrogen receptor modulator and a drug previously linked with retinal toxicity, paradoxically provided potent neuroprotective effects. In a light-induced degeneration model, tamoxifen prevented onset of photoreceptor apoptosis and atrophy and maintained near-normal levels of electroretinographic responses. Rescue effects were correlated with decreased microglial activation and inflammatory cytokine production in the retina in vivo and a reduction of microglia-mediated toxicity to photoreceptors in vitro, indicating a microglia-mediated mechanism of rescue. Tamoxifen also rescued degeneration in a genetic (Pde6b(rd10)) model of RP, significantly improving retinal structure, electrophysiological responses, and visual behavior. These prominent neuroprotective effects warrant the consideration of tamoxifen as a drug suitable for being repurposed to treat photoreceptor degenerative disease.SIGNIFICANCE STATEMENT Photoreceptor degeneration is a cause of irreversible blindness in a number of retinal diseases such as retinitis pigmentosa (RP) and atrophic age-related macular degeneration. Tamoxifen, a selective estrogen receptor modulator approved for the treatment of breast cancer and previously linked to a low incidence of retinal toxicity, was unexpectedly found to exert marked protective effects against photoreceptor degeneration. Structural and functional protective effects were found for an acute model of light-induced photoreceptor injury and for a genetic model for RP. The mechanism of protection involved the modulation of microglial activation and the production of inflammatory cytokines, highlighting the role of inflammatory mechanisms in photoreceptor degeneration. Tamoxifen may be

  6. Storm fronts over galaxy discs: models of how waves generate extraplanar gas and its anomalous kinematics

    NASA Astrophysics Data System (ADS)

    Struck, Curtis; Smith, Daniel C.

    2009-09-01

    The existence of partially ionized, diffuse gas and dust clouds at kiloparsec scale distances above the central planes of edge-on, galaxy discs was an unexpected discovery about 20 years ago. Subsequent observations showed that this extended or extraplanar diffuse interstellar gas (EDIG) has rotation velocities approximately 10-20 per cent lower than those in the central plane, and has been hard to account for. Here, we present results of hydrodynamic models, with radiative cooling and heating from star formation. We find that in models with star formation generated stochastically across the disc, an extraplanar gas layer is generated as long as the star formation is sufficiently strong. However, this gas rotates at nearly the same speed as the midplane gas. We then studied a range of models with imposed spiral or bar waves in the disc. EDIG layers were also generated in these models, but primarily over the wave regions, not over the entire disc. Because of this partial coverage, the EDIG clouds move radially, as well as vertically, with the result that observed kinematic anomalies are reproduced. The implication is that the kinematic anomalies are the result of three-dimensional motions when the cylindrical symmetry of the disc is broken. Thus, the kinematic anomalies are the result of bars or strong waves, and more face-on galaxies with such waves should have an asymmetric EDIG component. The models also indicate that the EDIG can contain a significant fraction of cool gas, and that some star formation can be triggered at considerable heights above the disc mid-plane. We expect all of these effects to be more prominent in young, forming discs, to play a role in rapidly smoothing disc asymmetries and in working to self-regulate disc structure.

  7. Thermal Modeling of Disc Brake Rotor in Frictional Contact

    NASA Astrophysics Data System (ADS)

    Ali, Belhocine; Ghazaly, Nouby Mahdi

    2013-01-01

    Safety aspect in automotive engineering has been considered as a number one priority in development of new vehicle. Each single system has been studied and developed in order to meet safety requirement. Instead of having air bag, good suspension systems, good handling and safe cornering, there is one most critical system in the vehicle which is brake systems. The objective of this work is to investigate and analyze the temperature distribution of rotor disc during braking operation using ANSYS Multiphysics. The work uses the finite element analysis techniques to predict the temperature distribution on the full and ventilated brake disc and to identify the critical temperature of the rotor. The analysis also gives us, the heat flux distribution for the two discs.

  8. Exosomes as potential alternatives to stem cell therapy for intervertebral disc degeneration: in-vitro study on exosomes in interaction of nucleus pulposus cells and bone marrow mesenchymal stem cells.

    PubMed

    Lu, Kang; Li, Hai-Yin; Yang, Kuang; Wu, Jun-Long; Cai, Xiao-Wei; Zhou, Yue; Li, Chang-Qing

    2017-05-10

    The stem cell-based therapies for intervertebral disc degeneration have been widely studied. However, the mechanisms of mesenchymal stem cells interacting with intervertebral disc cells, such as nucleus pulposus cells (NPCs), remain unknown. Exosomes as a vital paracrine mechanism in cell-cell communication have been highly focused on. The purpose of this study was to detect the role of exosomes derived from bone marrow mesenchymal stem cells (BM-MSCs) and NPCs in their interaction with corresponding cells. The exosomes secreted by BM-MSCs and NPCs were purified by differential centrifugation and identified by transmission electron microscope and immunoblot analysis of exosomal marker proteins. Fluorescence confocal microscopy was used to examine the uptake of exosomes by recipient cells. The effects of NPC exosomes on the migration and differentiation of BM-MSCs were determined by transwell migration assays and quantitative RT-PCR analysis of NPC phenotypic genes. Western blot analysis was performed to examine proteins such as aggrecan, sox-9, collagen II and hif-1α in the induced BM-MSCs. Proliferation and the gene expression profile of NPCs induced by BM-MSC exosomes were measured by Cell Counting Kit-8 and qRT-PCR analysis, respectively. Both the NPCs and BM-MSCs secreted exosomes, and these exosomes underwent uptake by the corresponding cells. NPC-derived exosomes promoted BM-MSC migration and induced BM-MSC differentiation to a nucleus pulposus-like phenotype. BM-MSC-derived exosomes promoted NPC proliferation and healthier extracellular matrix production in the degenerate NPCs. Our study indicates that the exosomes act as an important vehicle in information exchange between BM-MSCs and NPCs. Given a variety of functions and multiple advantages, exosomes alone or loaded with specific genes and drugs would be an appropriate option in a cell-free therapy strategy for intervertebral disc degeneration.

  9. The relationship between obesity, low back pain, and lumbar disc degeneration when genetics and the environment are considered: a systematic review of twin studies.

    PubMed

    Dario, Amabile B; Ferreira, Manuela L; Refshauge, Kathryn M; Lima, Thais S; Ordoñana, Juan R; Ferreira, Paulo H

    2015-05-01

    The relationships between obesity and low back pain (LBP) and lumbar disc degeneration (LDD) remain unclear. It is possible that familial factors, including genetics and early environment, affect these relationships. To investigate the relationship between obesity-related measures (eg, weight, body mass index [BMI]) and LBP and LDD using twin studies, where the effect of genetics and early environment can be controlled. A systematic review with meta-analysis. MEDLINE, CINAHL, Scopus, Web of Science, and EMBASE databases were searched from the earliest records to August 2014. All cross-sectional and longitudinal observational twin studies identified by the search strategy were considered for inclusion. Two investigators independently assessed the eligibility, conducted the quality assessment, and extracted the data. Metaanalyses (fixed or random effects, as appropriate) were used to pool studies' estimates of association. In total, 11 articles met the inclusion criteria. Five studies were included in the LBP analysis and seven in the LDD analysis. For the LBP analysis, pooling of the five studies showed that the risk of having LBP for individuals with the highest levels of BMI or weight was almost twice that of people with a lower BMI (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.6-2.0; I(2)=0%). A dose-response relationship was also identified. When genetics and the effects of a shared early environment were adjusted for using a within-pair twin case-control analysis, pooling of three studies showed a reduced but statistically positive association between obesity and prevalence of LBP (OR 1.5; 95% CI 1.1-2.1; I(2)=0%). However, the association was further diminished and not significant (OR 1.4; 95% CI 0.8-2.3; I(2)=0%) when pooling included two studies on monozygotic twin pairs only. Seven studies met the inclusion criteria for LDD. When familial factors were not controlled for, body weight was positively associated with LDD in all five cross

  10. The Paracrine Effect of Degenerated Disc Cells on Healthy Human Nucleus Pulposus Cells Is Mediated by MAPK and NF-κB Pathways and Can Be Reduced by TGF-β1.

    PubMed

    Cai, Feng; Zhu, Lei; Wang, Feng; Shi, Rui; Xie, Xin-Hui; Hong, Xin; Wang, Xiao-Hu; Wu, Xiao-Tao

    2017-02-01

    Inflammation is thought to have a major role in the pathogenesis of disc degeneration. Studies have shown that nucleus pulposus cells (NPCs) respond to one or two specific cytokines by regulating cell proliferation or matrix synthesis. However, the effects of a cocktail of factors secreted by degenerated disc cells on transplanted exogenous healthy NPCs remain unknown. Concentrations of multiple cytokines in degenerated disc tissue-conditioned medium (dCM) were measured using enzyme-linked immunosorbent assay (ELISA). 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and Ki67 immunofluorescence staining were used to evaluate the proliferation of cells in dCM. The function of exogenous NPCs cultured in dCM was evaluated by examining catabolic markers (ADAMTS-4, ADAMTS-5, MMP-1, MMP-3, and MMP-13), anabolic markers (TIMP-1, TIMP-2, and TIMP-3), and the extracellular matrix protein-aggrecan (ACAN) and collagen II (COL2)-expression with real time polymerase chain reaction (RT-PCR). Mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathway activation was observed using Western blotting. Finally, we examined the role of transforming growth factor (TGF)-β1 in reducing dCM-mediated exogenous NPC dysfunction. Levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-1α, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, interferon-γ (IFN-γ), and prostaglandin E2 (PGE2) were higher and TGF-β1 levels were lower in dCM compared with the control medium. Treatment with dCM increased the proliferation of healthy NPCs. NPCs exhibited significantly higher expression of ADAMTS-4, ADAMTS-5, MMP-1, MMP-3, and MMP-13 and decreased TIMP-2, ACAN, and COL2 expression in the dCM group in a dose- and time-dependent manner. Treatment with dCM moderately increased TIMP-1 expression and had no effect on TIMP-3 mRNA levels. The MAPK and NF-κB pathways were implicated in dCM-mediated responses of healthy NPCs. TGF-β1 partially reversed the d

  11. Effects of Transplantation of hTIMP1-Expressing Bone Marrow Mesenchymal Stem Cells on the Extracellular Matrix of Degenerative Intervertebral Discs in an in vivo Rabbit Model.

    PubMed

    Yi, Zhou; Guanjun, Tu; Lin, Cong; Zifeng, Pei

    2014-04-08

    Study Design. Prospective, randomized controlled animal study.Objective. To observe ECM changes in degenerative IVD after transplantation of bone marrow mesenchymal stem cells (BMSCs) virally transfected with a construct expressing human tissue inhibitor of metalloproteinase 1 (hTIMP-1), and to discuss the feasibility of using this approach to treat intervertebral disc degeneration (IDD).Summary of Background Data. Intervertebral disc (IVD) degeneration is characterized by decreased cell numbers, bioactivity of the nucleus pulposus (NP), and remodeled extracellular matrix (ECM). Exogenous genes can be targeted into cells to produce inhibition of ECM degradation and increase ECM content in IVDs, and thereby potentially stop or reverse degenerative processes and modify disc structure.Methods. BMSCs were isolated from a pure New-Zealand rabbit and identified by flow cytometry. Transgenic BMSCs were acquired by transfection with a recombinant adenovirus vector carrying the hTIMP-1 gene. Animal models of IDD were established by annulus puncture and then given intra-NP injections according to their random assignment into three groups: (1) a transgenic BMSC transplantation (TgBT) group that received BMSCs transfected with an hTIMP-1-expressing adenovirus vector; (2) a BMSC transplantation (BT) group that received unaltered BMSCs; and (3) a control (PCon) group that received cell-free phosphate-buffered saline. Degree of degeneration was evaluated 12 wks after modeling. ECM content was quantified using immunohistochemistry (IHC) and spectrophotography. Expression of hTIMP-1 was observed via quantitative PCR, western blot, and IHC.Results. Significantly fewer degenerative changes and increased ECM content were observed in the TBT and BT groups compared to PCon animals (P < .05). The TBT group had greater ECM content than did the BT group (P < .05), as well as higher levels of hTIMP-1 mRNA and protein.Conclusions. Transplantation of BMSCs transfected with hTIMP-1 can

  12. Magnetorotationally driven wind cycles in local disc models

    NASA Astrophysics Data System (ADS)

    Riols, A.; Ogilvie, G. I.; Latter, H.; Ross, J. P.

    2016-12-01

    Jets, from the protostellar to the AGN context, have been extensively studied but their connection to the turbulent dynamics of the underlying accretion disc is poorly understood. Following a similar approach to Lesur, Fereira & Ogilvie, we examine the role of the magnetorotational instability (MRI) in the production and acceleration of outflows from discs. Via a suite of 1D shearing-box simulations of stratified discs, we show that magnetocentrifugal winds exhibit cyclic activity with a period of 10-20 Ω-1, a few times the orbital period. The cycle seems to be more vigorous for strong vertical field; it is robust to the variation of relevant parameters and independent of numerical details. The convergence of these solutions (in particular the mass-loss rate) with vertical box size is also studied. By considering a sequence of magnetohydrostatic equilibria and their stability, the periodic activity may be understood as the succession of the following phases: (a) a dominant MRI channel mode, (b) strong magnetic field generation, (c) consequent wind launching, and ultimately (d) vertical expulsion of the excess magnetic field by the expanding and accelerating gas associated with the wind. We discuss potential connections between this behaviour and observed time-variability in disc-jet systems.

  13. Numerical Modeling of Tidal Effects in Polytropic Accretion Discs

    NASA Technical Reports Server (NTRS)

    Godon, P.

    1996-01-01

    A two-dimensional time-dependent hybrid Fourier-Chebyshev method of collocation is developed and used for the study of tidal effects in accretion discs, under the assumption of a polytropic equation of state and a standard alpha viscosity prescription.

  14. Modeling the Compact Disc Read System in Lab

    ERIC Educational Resources Information Center

    Hinaus, Brad; Veum, Mick

    2009-01-01

    One of the great, engaging aspects of physics is its application to everyday technology. The compact disc player is an example of one such technology that applies fundamental principles from optics in order to efficiently store and quickly retrieve information. We have created a lab in which students use simple optical components to assemble a…

  15. Modeling the Compact Disc Read System in Lab

    ERIC Educational Resources Information Center

    Hinaus, Brad; Veum, Mick

    2009-01-01

    One of the great, engaging aspects of physics is its application to everyday technology. The compact disc player is an example of one such technology that applies fundamental principles from optics in order to efficiently store and quickly retrieve information. We have created a lab in which students use simple optical components to assemble a…

  16. A two-fluid model for black-hole accretion flows: particle acceleration and disc structure

    NASA Astrophysics Data System (ADS)

    Lee, Jason P.; Becker, Peter A.

    2017-02-01

    Hot, tenuous advection-dominated accretion flows around black holes are ideal sites for the Fermi acceleration of relativistic particles at standing shock waves in the accretion disc. Previous work has demonstrated that the shock-acceleration process can be efficient enough to power the observed, strong outflows in radio-loud active galaxies such as M87. However, the dynamical effect (back-reaction) on the flow, exerted by the pressure of the relativistic particles, has not been previously considered, and this effect can have a significant influence on the disc structure. We reexamine the problem by developing a new, two-fluid model for the structure of the accretion disc that includes the dynamical effect of the relativistic particle pressure, combined with the pressure of the background (thermal) gas. The new model is analogous to the two-fluid model of cosmic ray acceleration in supernova-driven shock waves. As part of the model, we also develop a new set of shock jump conditions, which are solved along with the hydrodynamic conservation equations to determine the structure of the accretion disc. The solutions include the formation of a mildly relativistic outflow (jet) at the shock radius, driven by the relativistic particles accelerated in the disc. One of our main conclusions is that in the context of the new two-fluid accretion model, global smooth (shock-free) solutions do not exist, and the disc must always contain a standing shock wave, at least in the inviscid case considered here.

  17. The pseudo-photosphere model for the continuum emission of gaseous discs

    NASA Astrophysics Data System (ADS)

    Vieira, R. G.; Carciofi, A. C.; Bjorkman, J. E.

    2015-12-01

    We investigate the continuum emission of viscous decretion discs around Be stars in this paper. The results obtained from non-LTE (local thermodynamic equilibrium) radiative transfer models show two regimes in the disc surface brightness profile: an inner optically thick region, which behaves as a pseudo-photosphere with a wavelength-dependent size, and an optically thin tenuous outer part, which contributes with about a third of the total flux. The isophotal shape of the surface brightness is well described by elliptical contours with an axial ratio b/a = cos i for inclinations i < 75°. Based on these properties, a semi-analytical model was developed to describe the continuum emission of gaseous discs. It provides fluxes and spectral slopes at the infrared within an accuracy of 10 and 5 per cent, respectively, when compared to the numerical results. The model indicates that the infrared spectral slope is mainly determined by both the density radial slope and the disc flaring exponent, being practically independent of disc inclination and base density. As a first application, the density structure of 15 Be stars was investigated, based on the infrared flux excess, and the results compared to previous determinations in the literature. Our results indicate that the decretion rates are in the range of 10-12-10-9 M⊙ yr-1, which is at least two orders of magnitude smaller than the previous outflowing disc model predictions.

  18. Development and Translation of a Tissue-Engineered Disc in a Preclinical Rodent Model

    DTIC Science & Technology

    2014-12-01

    surgery and fixation conditions are the same, but without disc removal or DAPS placement. Given that Aims 2 and Aim 3 are both in vivo...Development of an Engineered Disc Implantation Model in the Rat Caudal Spine: Our first step in this work was pilot surgeries (with a few...technique was designed to be minimally invasive in order to prevent vascular damage and promote rapid healing. Three surgical groups were evaluated: sham

  19. The circumstellar disc in the Bok globule CB 26. Multi-wavelength observations and modelling of the dust disc and envelope

    NASA Astrophysics Data System (ADS)

    Sauter, J.; Wolf, S.; Launhardt, R.; Padgett, D. L.; Stapelfeldt, K. R.; Pinte, C.; Duchêne, G.; Ménard, F.; McCabe, C.-E.; Pontoppidan, K.; Dunham, M.; Bourke, T. L.; Chen, J.-H.

    2009-10-01

    Context: Circumstellar discs are expected to be the nursery of planets. Grain growth within such discs is the first step in the planet formation process. The Bok globule CB 26 harbours such a young disc. Aims: We present a detailed model of the edge-on circumstellar disc and its envelope in the Bok globule CB 26. Methods: The model is based on HST near-infrared maps in the I, J, H, and K bands, OVRO and SMA radio maps at 1.1 mm, 1.3 mm and 2.7 mm, and the spectral energy distribution (SED) from 0.9 {μ m} to 3 mm. New photometric and spectroscopic data from the Spitzer Space Telescope and the Caltech Submilimeter Observatory are also part of our analysis. Using the self-consistent radiative transfer code MC3D, the model we construct is able to discriminate between parameter sets and dust properties of both envelope and disc. Results: We find that the data are fit by a disc that has an inner hole with a radius of 45±5 AU. Based on a dust model including silicate and graphite, the maximum grain size needed to reproduce the spectral millimetre index is 2.5 {μ m}. Features seen in the near-infrared images, dominated by scattered light, can be described as a result of a rotating envelope. Conclusions: Successful employment of ISM dust in both the disc and envelope hint that grain growth may not yet play a significant role for the appearance of this system. A large inner hole implies that CB 26 is a circumbinary disc.

  20. Dark energy density in SUGRA models and degenerate vacua

    NASA Astrophysics Data System (ADS)

    Froggatt, C. D.; Nielsen, H. B.; Nevzorov, R.; Thomas, A. W.

    2017-06-01

    In N=1 supergravity the tree-level scalar potential of the hidden sector may have a minimum with broken local supersymmetry (SUSY) as well as a supersymmetric Minkowski vacuum. These vacua can be degenerate, allowing for a consistent implementation of the multiple point principle. The first minimum where SUSY is broken can be identified with the physical phase in which we live. In the second supersymmetric phase, in flat Minkowski space, SUSY may be broken dynamically either in the observable or in the hidden sectors inducing a tiny vacuum energy density. We argue that the exact degeneracy of these phases may shed light on the smallness of the cosmological constant. Other possible phenomenological implications are also discussed. In particular, we point out that the presence of such degenerate vacua may lead to small values of the quartic Higgs coupling and its beta function at the Planck scale in the physical phase.

  1. A finite element model of the L4-L5-S1 human spine segment including the heterogeneity and anisotropy of the discs.

    PubMed

    Jaramillo, Hector E; Gómez, Lessby; García, Jose J

    2015-01-01

    With the aim to study disc degeneration and the risk of injury during occupational activities, a new finite element (FE) model of the L4-L5-S1 segment of the human spine was developed based on the anthropometry of a typical Colombian worker. Beginning with medical images, the programs CATIA and SOLIDWORKS were used to generate and assemble the vertebrae and create the soft structures of the segment. The software ABAQUS was used to run the analyses, which included a detailed model calibration using the experimental step-wise reduction data for the L4-L5 component, while the L5-S1 segment was calibrated in the intact condition. The range of motion curves, the intradiscal pressure and the lateral bulging under pure moments were considered for the calibration. As opposed to other FE models that include the L5-S1 disc, the model developed in this study considered the regional variations and anisotropy of the annulus as well as a realistic description of the nucleus geometry, which allowed an improved representation of experimental data during the validation process. Hence, the model can be used to analyze the stress and strain distributions in the L4-L5 and L5-S1 discs of workers performing activities such as lifting and carrying tasks.

  2. Probabilistic Fatigue Life Prediction of Turbine Disc Considering Model Parameter Uncertainty

    NASA Astrophysics Data System (ADS)

    He, Liping; Yu, Le; Zhu, Shun-Peng; Ding, Liangliang; Huang, Hong-Zhong

    2016-06-01

    Aiming to improve the predictive ability of Walker model for fatigue life prediction and taking the turbine disc alloy GH4133 as the application example, this paper investigates a new approach for probabilistic fatigue life prediction when considering parameter uncertainty inherent in the life prediction model. Firstly, experimental data are used to update the model parameters using Bayes' theorem, so as to obtain the posterior probability distribution functions of two parameters of the Walker model, as well to achieve the probabilistic life prediction model for turbine disc. During the updating process, Markov Chain Monte Carlo (MCMC) technique is used to generate samples of the given distribution and estimating the parameters distinctly. After that, the turbine disc life is predicted using the probabilistic Walker model based on Monte Carlo simulation technique. The experimental results indicate that: (1) after using the small sample test data obtained from turbine disc, parameter uncertainty of the Walker model can be quantified and the corresponding probabilistic model for fatigue life prediction can be established using Bayes' theorem; (2) there exists obvious dispersion of life data for turbine disc when predicting fatigue life in practical engineering application.

  3. High-resolution optical coherence tomography in mouse models of genetic and induced retinal degeneration

    NASA Astrophysics Data System (ADS)

    Cimalla, Peter; Carido, Madalena; Pran Babu, Sheik; Santos-Ferreira, Tiago; Gaertner, Maria; Kordowich, Simon; Wittig, Dierk; Ader, Marius; Karl, Mike; Koch, Edmund

    2013-06-01

    For the study of disease mechanisms and the development of novel therapeutic strategies for retinal pathologies in human, rodent models play an important role. Nowadays, optical coherence tomography (OCT) allows three-dimensional investigation of retinal events over time. However, a detailed analysis of how different retinal degenerations are reflected in OCT images is still lacking in the biomedical field. Therefore, we use OCT to visualize retinal degeneration in specific mouse models in order to study disease progression in vivo and improve image interpretation of this noninvasive modality. We use a self-developed spectral domain OCT system for simultaneous dual-band imaging in the 0.8 μm- and 1.3 μm-wavelength range - the two most common spectral bands in biomedical OCT. A fiber-coupled ophthalmic scanning unit allows flexible imaging of the eye with a high axial resolution of 3 - 4 μm in tissue. Four different mouse models consisting of one genetic (rhodopsin-deficient and three induced retinal degenerations (sodium iodate-induced damage, light-induced photoreceptor damage and Kainate neurotoxin damage) were investigated. OCT imaging was performed daily or weekly, depending on the specific degeneration model, over a time period of up to 9 weeks. Individual retinal layers that were affected by the specific degeneration could successfully be identified and monitored over the observation time period. Therefore, longitudinal OCT studies deliver reliable information about the retinal microstructure and the time course of retinal degeneration processes in vivo.

  4. Effect of collagen fibre orientation on intervertebral disc torsion mechanics.

    PubMed

    Yang, Bo; O'Connell, Grace D

    2017-07-21

    The intervertebral disc is a complex fibro-cartilaginous material, consisting of a pressurized nucleus pulposus surrounded by the annulus fibrosus, which has an angle-ply structure. Disc injury and degeneration are noted by significant changes in tissue structure and function, which significantly alters stress distribution and disc joint stiffness. Differences in fibre orientation are thought to contribute to changes in disc torsion mechanics. Therefore, the objective of this study was to evaluate the effect of collagen fibre orientation on internal disc mechanics under compression combined with axial rotation. We developed and validated a finite element model (FEM) to delineate changes in disc mechanics due to fibre orientation from differences in material properties. FEM simulations were performed with fibres oriented at [Formula: see text] throughout the disc (uniform by region and fibre layer). The initial model was validated by published experimental results for two load conditions, including [Formula: see text] axial compression and [Formula: see text] axial rotation. Once validated, fibre orientation was rotated by [Formula: see text] or [Formula: see text] towards the horizontal plane, resulting in a decrease in disc joint torsional stiffness. Furthermore, we observed that axial rotation caused a sinusoidal change in disc height and radial bulge, which may be beneficial for nutrient transport. In conclusion, including anatomically relevant fibre angles in disc joint FEMs is important for understanding stress distribution throughout the disc and will be important for understanding potential causes for disc injury. Future models will include regional differences in fibre orientation to better represent the fibre architecture of the native disc.

  5. Residual stresses in a quenched superalloy turbine disc: Measurements and modeling

    NASA Astrophysics Data System (ADS)

    Rist, M. A.; James, J. A.; Tin, S.; Roder, B. A.; Daymond, M. R.

    2006-02-01

    A series of neutron diffraction measurements have been carried out to determine the elastic residual strains deep within a large, 40-cm-diameter, forged and water-quenched IN718 aeroengine compressor disc. Neutron path lengths of up to 6 cm were necessary to probe the thickest parts of the forging, and three-dimensional strain and stress components have been derived for the first time in such a large superalloy specimen. Measurements have been compared with the results from a coupled thermal-mechanical finite-element model of the quenching process, based upon appropriate temperature-dependent material properties, with some success. The general residual stress state in the disc is one of near-surface compression, balanced by tension within the disc interior. The steepest stress and strain gradients occur in the transition region from compression to tension, about 1 cm below the surface all around the disc. The largest stress component is in the disc tangential direction and reaches a magnitude of 400 to 500 MPa near the disc surface and at its core. This exceeds the effective yield stress because of the presence of significant hydrostatic stress.

  6. Accretion discs models with the β-viscosity prescription derived from laboratory experiments

    NASA Astrophysics Data System (ADS)

    Huré, J.-M.; Richard, D.; Zahn, J.-P.

    2001-03-01

    We examine under which conditions one may apply, to steady state Keplerian accretion discs, the beta -viscosity prescription which has been derived from rotating shear flow experiments (nu = beta Omega R2, where Omega is the angular velocity at radius R and beta is a constant of order 10-5; Richard & Zahn \\cite{richard99}). Using a vertically averaged model, we show that this law may be suitable for all three families of known systems: in young stellar objects, evolved binary stars and Active Galactic Nuclei discs (except in their outer gas pressure dominated regions where turbulence becomes hypersonic). According to the standard criterion for viscous stability, beta -discs are always stable throughout. Using realistic opacities and equation of state, we demonstrate that these discs are thermally unstable in the temperature domain where hydrogen recombines, when they are optically thick, and this could lead to limit cycle behavior. Radiation pressure dominated regions are thermally stable, in contrast with alpha -discs. This results in a fully stable solution for the innermost parts of AGN discs.

  7. Weld restoration of the first stage disc of a Westinghouse Model 501AA gas turbine

    SciTech Connect

    Niewiara, W.; Cline, W.

    1995-12-31

    With the advancement of dimensional data retrieval systems, analytical tools and specialized welding techniques, along with sound metallurgical evaluation, repair technology has progressed to the point where turbonmachinery repairs can be structurally and metallurgically superior to the original design. A case in point is the weld repair of the Westinghouse Model 501AA first stage gas turbine disc. The surfaces of the disc had experienced severe corrosion damage, particularly in the fir tree blade attachment areas. The repair required a disc rim rebuild in which the circumferential root attachment area was removed by machining, restored using the mechanized Submerged Arc Welding (SAW) process and final machined to original design specifications. This paper will discuss the engineering effort used to restore the damaged gas turbine disc. Included in the engineering effort were the dimensional inspections used to restore the damaged gas turbine disc. Included in the engineering effort were the dimensional inspections used for generating machining drawings, finite element thermal and stress analyses, and a complete metallurgical evaluation to determine the appropriate weld filler material. The weld repair and heat treatment procedures will be outlined, as will be the final machining and final dimensional inspection. The materials used for this application provide excellent mechanical and metallurgical properties with improved corrosion and creep resistance for longer component life. The weld procedure has been standardized and has been performed successfully on several discs of similar design.

  8. The Bosma effect revisited. I. HI and stellar disc scaling models

    NASA Astrophysics Data System (ADS)

    Hessman, F. V.; Ziebart, M.

    2011-08-01

    Context. The observed proportionality between the centripetal contribution of the dynamically insignificant HI gas in the discs of spiral galaxies and the dominant contribution of dark matter (DM) - the "Bosma effect" - has been repeatedly mentioned in the literature but largely ignored. Since this phenomenology, if statistically significant, tells us something about the relationship between the visible baryonic and invisible DM, it is important to re-examine the reality of this effect using formal tests and more modern data. Aims: We have re-examined the evidence for the Bosma effect, either by scaling the contribution of the HI gas alone or by using both the observed stellar disc and HI gas as proxies. Methods: We have calculated Bosma effect models for 17 galaxies in The HI Nearby Galaxy Survey data set. The results are compared with two models for exotic cold DM: internally consistent cosmological Navarro-Frenk-White (NFW) models with constrained compactness parameters, and "universal rotation curve" (URC) models using fully unconstrained Burkert density profiles. Results: Fits to spiral galaxy rotation curves computed using just HI scaling are inadequate, despite the clear proportionality seen in the outer discs. The poor performance is obviously related to the prominent decrease in the HI surface density in regions of high stellar surface density, where HI has been converted into molecules and stars. The Bosma models that partially correct for this physical effect using the stellar discs as additional proxies are statistically nearly as good as the URC models and clearly better than the NFW ones. Conclusions: We confirm the correlation between the centripetal effects of DM and that of the interstellar medium of spiral galaxies. The efficacy of "maximal disc" models is explained as the natural consequence of "classic" Bosma models which include the stellar disc as a proxy in regions of reduced atomic gas. The perception that the Bosma effect could be due to

  9. Simulating the sensitivity of cell nutritive environment to composition changes within the intervertebral disc

    NASA Astrophysics Data System (ADS)

    Wills, C. Ruiz; Malandrino, A.; van Rijsbergen, MM.; Lacroix, D.; Ito, K.; Noailly, J.

    2016-05-01

    Altered nutrition in the intervertebral disc affects cell viability and can generate catabolic cascades contributing to extracellular matrix (ECM) degradation. Such degradation is expected to affect couplings between disc mechanics and nutrition, contributing to accelerate degenerative processes. However, the relation of ECM changes to major biophysical events within the loaded disc remains unclear. A L4-L5 disc finite element model including the nucleus (NP), annulus (AF) and endplates was used and coupled to a transport-cell viability model. Solute concentrations and cell viability were evaluated along the mid-sagittal plane path. A design of experiment (DOE) was performed. DOE parameters corresponded to AF and NP biochemical tissue measurements in discs with different degeneration grades. Cell viability was not affected by any parameter combinations defined. Nonetheless, the initial water content was the parameter that affected the most the solute contents, especially glucose. Calculations showed that altered NP composition could negatively affect AF cell nutrition. Results suggested that AF and NP tissue degeneration are not critical to nutrition-related cell viability at early-stage of disc degeneration. However, small ECM degenerative changes may alter significantly disc nutrition under mechanical loads. Coupling disc mechano-transport simulations and enzyme expression studies could allow identifying spatiotemporal sequences related to tissue catabolism.

  10. Precipitation Model Validation in 3rd Generation Aeroturbine Disc Alloys

    NASA Technical Reports Server (NTRS)

    Olson, G. B.; Jou, H.-J.; Jung, J.; Sebastian, J. T.; Misra, A.; Locci, I.; Hull, D.

    2008-01-01

    In support of application of the DARPA-AIM methodology to the accelerated hybrid thermal process optimization of 3rd generation aeroturbine disc alloys with quantified uncertainty, equilibrium and diffusion couple experiments have identified available fundamental thermodynamic and mobility databases of sufficient accuracy. Using coherent interfacial energies quantified by Single-Sensor DTA nucleation undercooling measurements, PrecipiCalc(TM) simulations of nonisothermal precipitation in both supersolvus and subsolvus treated samples show good agreement with measured gamma particle sizes and compositions. Observed longterm isothermal coarsening behavior defines requirements for further refinement of elastic misfit energy and treatment of the parallel evolution of incoherent precipitation at grain boundaries.

  11. [Change and Significance of RhoA/ROCK signaling pathway in the model with natural degeneration of the rat endplate chondrocytes].

    PubMed

    Ma, Mingming; Xu, Hongguang; Zhang, Xiaoling; Wang, Hong; Zheng, Quan; Xu, Jiajia; Shen, Xiang; Zhang, Shufeng

    2015-11-03

    To explore the change and Significance of RhoA/ROCK signaling pathway in the model with natural degeneration of the rat endplate chondrocytes. Endplate chondrocytes were selected by enzyme digestion and cultured in vitro to divided into control (P2 cells), naturally passaged (P5 cells) groups and treatment group (P5+ROCK Inhibitor Y27632). The phenotype of endplate chondrocytes were identified by toluidine blue stains and F-actin stains. Type II collagen, aggrecan and SOX9 genes were examed by Real-time RT-PCR to verify the degeneration model. The RhoA/ROCK signaling pathway related gene ROCK-1, ROCK-2 were detected by RT-PCR and Western blot. The actived RhoA was examed by active-RhoA detection and Western blot. With the passaging,endplate chondrocytes completely lost the original cell morphology, the levels of type II collagen (P5/P2=0.248, P<0.001), aggrecan (P5/P2=0.172, P<0.001) and SOX9 (P5/P2 =0.499, P<0.001) significantly reduced. There is also a certain reduction of ROCK-1 (P5/P2=0.652, P<0.001), but ROCK-2 (P5/P2=2.527, P<0.001) expression increased significantly. And the active-RhoA were Significant increased too.ROCK-1 AND ROCK-2 were down-regulated in the treatment group. And type II collagen, aggrecan, SOX9 significantly increased. The degeneration of endplate chondrocytes with decreased ROCK-1 expression but increased active-RhoA and ROCK-2 expression suggest that RhoA/ROCK signaling pathway play an important role in the in vitro degeneration of endplate chondrocytes.Modulating the expression of RhoA/ROCK signaling pathway may be a new method of solving the problem of the degeneration of intervertebral disc.

  12. Formation of disc galaxies in preheated media: a preventative feedback model

    NASA Astrophysics Data System (ADS)

    Lu, Yu; Mo, H. J.; Wechsler, Risa H.

    2015-01-01

    We develop a semi-analytic galaxy formation model that implements a self-consistent treatment for the hot halo gas and the assembly of central discs. We use the model to explore a preventative feedback scenario, in which the circumhalo medium is assumed to be preheated up to a certain entropy level by early starbursts or other processes, and contrast it with an ejective feedback scenario in which baryons are first accreted into dark matter haloes and subsequently ejected by feedback. When the preheating entropy is comparable to the halo virial entropy, baryon accretion can be reduced and delayed. The accreted medium establishes an extended gaseous halo, and the cooling gas that forms the central disc has a higher specific angular momentum than the halo material. The preventative feedback model can reproduce remarkably well a number of observational scaling relations, including the cold baryon mass fraction-halo mass relations, star formation histories, disc size-stellar mass relation and its evolution, and the evolution of the number density of low-mass galaxies. In contrast, the ejective feedback model fails to reproduce these observational trends. These results show that the properties of disc galaxies are closely tied to the thermal state of hot halo gas and perhaps also the circumhalo medium, which suggests that observations of the disc properties and circumgalactic hot/warm medium may jointly provide important constraints on galaxy formation.

  13. A biphasic finite element model of in vitro plowing tests of the temporomandibular joint disc.

    PubMed

    Spilker, R L; Nickel, J C; Iwasaki, L R

    2009-06-01

    Disorders of the temporomandibular joint (TMJ) afflict 3-29% of people aged 19-40 years. Degenerative joint disease (DJD) of the TMJ generally occurs 15 years earlier than in other human joints and 1.5-2 times more often in women than men. The TMJ disc is the primary stress distribution mechanism within the joint. Mechanical failure of the TMJ disc precedes clinical signs of DJD. Unlike postcranial synovial joints, biomimetic replacements of the disc have not been successful, probably due to the paucity of knowledge about TMJ biomechanics. Translation of stress-fields mediolaterally across the TMJ disc may lead to fatigue failure because of the effect of traction forces on the tissue surface and because the disc is relatively weak in this aspect. Traction forces are composed of friction forces, which are known to be low in the TMJ, and plowing forces which are relatively much higher and result from movement and pressurization of fluids within the tissues due to translating surface loads. In the in vitro plowing experiment, a rigid curve-ended indenter is lowered into a TMJ disc that has been mounted on a stage with pressure gauges, and the indenter is then translated in a prescribed mediolateral motion that is intended to simulate the motion of the mandibular condyle on the TMJ disc in vivo. As a first step, these plowing experiments have quantified the variables thought to be important in tissue failure. A next step is to define the full role of these variables in the pathomechanics of TMJ disc tissue through a validated model. Therefore, the aim of this study was to develop and test a finite element model of the plowing experiments based on an orthotropic biphasic description of the soft tissue behavior of the TMJ disc. For this plowing model, the arbitrary Lagrange Eulerian method was used to approximate the moving load problem, where in vitro the indenter slid along the tissue's superior surface. Approximate validation of the plowing model was based on

  14. Retinal Changes in an ATP-Induced Model of Retinal Degeneration

    PubMed Central

    Aplin, Felix P.; Vessey, Kirstan A.; Luu, Chi D.; Guymer, Robyn H.; Shepherd, Robert K.; Fletcher, Erica L.

    2016-01-01

    In rodents and felines, intravitreal administration of adenosine triphosphate (ATP) has been shown to induce photoreceptor death providing a tractable model of retinal degeneration in these species. This study investigated the long term effects of photoreceptor loss in an ATP induced feline model of retinal degeneration. Six normal sighted felines were unilaterally blinded using intravitreal ATP injections and assessed using electroretinography (ERG) and optical coherence tomography (OCT). At 30 h (n = 3) or 12 weeks (n = 3) post-injection, the animals were euthanized and the eyes enucleated. Retinae were sectioned and labeled using immunohistochemistry for markers of cell death, neural remodeling and gliosis. Ongoing cell death and retinal degeneration was observed in the outer retina at both 30 h and 12 weeks following unilateral ATP injection. Markers of mid to late-stage retinal remodeling such as cell displacement and aberrant neurite growth were observed in the inner retina at 12 weeks post-injection. Ganglion cells appeared to remain intact in ATP injected eyes. Müller cell gliosis was observed throughout the inner and outer retina, in some parts completely enveloping and/or displacing the surviving neural tissue. Our data suggests that the ATP injected feline retina continues to undergo progressive retinal degeneration and exhibits abnormalities consistent with a description of retinal remodeling commonly seen in other models of retinal degeneration. These findings validate the use of intravitreal ATP injection in feline as a large animal model of retinal degeneration which may aid in development of therapies aiming to restore visual function after photoreceptor degeneration. PMID:27199678

  15. Retinal Changes in an ATP-Induced Model of Retinal Degeneration.

    PubMed

    Aplin, Felix P; Vessey, Kirstan A; Luu, Chi D; Guymer, Robyn H; Shepherd, Robert K; Fletcher, Erica L

    2016-01-01

    In rodents and felines, intravitreal administration of adenosine triphosphate (ATP) has been shown to induce photoreceptor death providing a tractable model of retinal degeneration in these species. This study investigated the long term effects of photoreceptor loss in an ATP induced feline model of retinal degeneration. Six normal sighted felines were unilaterally blinded using intravitreal ATP injections and assessed using electroretinography (ERG) and optical coherence tomography (OCT). At 30 h (n = 3) or 12 weeks (n = 3) post-injection, the animals were euthanized and the eyes enucleated. Retinae were sectioned and labeled using immunohistochemistry for markers of cell death, neural remodeling and gliosis. Ongoing cell death and retinal degeneration was observed in the outer retina at both 30 h and 12 weeks following unilateral ATP injection. Markers of mid to late-stage retinal remodeling such as cell displacement and aberrant neurite growth were observed in the inner retina at 12 weeks post-injection. Ganglion cells appeared to remain intact in ATP injected eyes. Müller cell gliosis was observed throughout the inner and outer retina, in some parts completely enveloping and/or displacing the surviving neural tissue. Our data suggests that the ATP injected feline retina continues to undergo progressive retinal degeneration and exhibits abnormalities consistent with a description of retinal remodeling commonly seen in other models of retinal degeneration. These findings validate the use of intravitreal ATP injection in feline as a large animal model of retinal degeneration which may aid in development of therapies aiming to restore visual function after photoreceptor degeneration.

  16. Stimulation of a Suprachoroidal Retinal Prosthesis Drives Cortical Responses in a Feline Model of Retinal Degeneration.

    PubMed

    Aplin, Felix P; Fletcher, Erica L; Luu, Chi D; Vessey, Kirstan A; Allen, Penelope J; Guymer, Robyn H; Shepherd, Robert K; Shivdasani, Mohit N

    2016-10-01

    Retinal prostheses have emerged as a promising technology to restore vision in patients with severe photoreceptor degeneration. To better understand how neural degeneration affects the efficacy of electronic implants, we investigated the function of a suprachoroidal retinal implant in a feline model. Unilateral retinal degeneration was induced in four adult felines by intravitreal injection of adenosine triphosphate (ATP). Twelve weeks post injection, animals received suprachoroidal electrode array implants in each eye, and responses to electrical stimulation were obtained using multiunit recordings from the visual cortex. Histologic measurements of neural and glial changes in the retina at the implant site were correlated with cortical thresholds from individual stimulating electrodes. Adenosine triphosphate-injected eyes displayed changes consistent with mid-to-late stage retinal degeneration and remodeling. A significant increase in electrical charge was required to induce a cortical response from stimulation of the degenerated retina compared to that in the fellow control eye. Spatial and temporal characteristics of the electrically evoked cortical responses were no different between eyes. Individual electrode thresholds varied in both the control and the ATP-injected eyes and were correlated with ganglion cell density. In ATP-injected eyes, cortical threshold was also independently correlated with an increase in the extent of retinal gliosis. These data suggest that even when ganglion cell density remains unaffected, glial changes in the retina following degeneration can influence the efficacy of suprachoroidal electrical stimulation. A better understanding of how glial change impacts retinal prosthesis function may help to further the optimization of retinal implants.

  17. Disc erosion in Models 103 and 104 of Beall mitral valve prostheses

    PubMed Central

    Gómez, Ricardo; Verduras, María José; Lopez-Quintana, Alfonso; Riera, Luis; Zerolo, Ignacio; Martinez-Bordiu, Cristóbal

    1981-01-01

    Three cases of severe disc variance and erosion of the Teflon-disc Beall mitral valve prosthesis (Models 103 and 104) are reported. In two patients, the Beall mitral valves were excised and replaced with two Björk-Shiley mitral valves. The remaining patient did not survive, and at autopsy, the lens was found at the aortic bifurcation level. Because of this potentially lethal complication, careful follow-up of patients with Beall mitral valve prostheses (Models 103 and 104) is recommended. Images PMID:15216211

  18. Disc erosion in Models 103 and 104 of Beall mitral valve prostheses.

    PubMed

    Gómez, Ricardo; Verduras, María José; Lopez-Quintana, Alfonso; Riera, Luis; Zerolo, Ignacio; Martinez-Bordiu, Cristóbal

    1981-06-01

    Three cases of severe disc variance and erosion of the Teflon-disc Beall mitral valve prosthesis (Models 103 and 104) are reported. In two patients, the Beall mitral valves were excised and replaced with two Björk-Shiley mitral valves. The remaining patient did not survive, and at autopsy, the lens was found at the aortic bifurcation level. Because of this potentially lethal complication, careful follow-up of patients with Beall mitral valve prostheses (Models 103 and 104) is recommended.

  19. LIM mineralization protein-1 suppresses TNF-α induced intervertebral disc degeneration by maintaining nucleus pulposus extracellular matrix production and inhibiting matrix metalloproteinases expression.

    PubMed

    Liu, Hui; Pan, Hehai; Yang, Hao; Wang, Jianru; Zhang, Kuibo; Li, Xiang; Wang, Hua; Ding, Wenbin; Li, Bingxue; Zheng, Zhaomin

    2015-03-01

    Imbalanced metabolism of Nucleus pulposus (NP) extracellular matrix (ECM) is closely correlated to Intervertebral Disc Degenerative Disease. LIM mineralization protein-1 (LMP-1) has been proven to induce sulfated glycosaminoglycan (sGAG) production in NP and have an anti-inflammatory effect in pre-osteoclast. However, whether it has any effect on the NP ECM production and degradation under inflammatory stimulation has not been studied. In the current study, a TNF-α induced cell model was established in vitro. Lentivirus encoding LMP-1 (LV-LMP-1) and short heparin LMP-1 (LV-shLMP-1) were constructed to overexpress and knockdown LMP-1 expression in NP cells. LMP-1 mRNA level was regulated in a dose-dependent manner after transfection. LV-LMP-1 increased whereas LV-shLMP-1 decreased collagen II, aggrecan, versican expression, and sGAG production. LV-LMP-1 abolished while LV-shLMP-1 aggravated TNF-α mediated down-regulation of the above matrix genes via ERK1/2 activation. Moreover, LV-LMP-1 abrogated TNF-α induced MMP-3 and MMP-13 expression via inhibiting p65 translocation and MMP-3 and MMP-13 promoter activity. These results indicated that LMP-1 had an ECM production maintenance effect under inflammatory stimulation. This effect was via up-regulation of matrix genes expression at least partially through ERK1/2 activation, and down-regulation of MMPs expression through NF-κB inhibition.

  20. Biomechanical changes of the lumbar segment after total disc replacement : charite(r), prodisc(r) and maverick(r) using finite element model study.

    PubMed

    Kim, Ki-Tack; Lee, Sang-Hun; Suk, Kyung-Soo; Lee, Jung-Hee; Jeong, Bi-O

    2010-06-01

    The purpose of this study was to analyze the biomechanical effects of three different constrained types of an artificial disc on the implanted and adjacent segments in the lumbar spine using a finite element model (FEM). The created intact model was validated by comparing the flexion-extension response without pre-load with the corresponding results obtained from the published experimental studies. The validated intact lumbar model was tested after implantation of three artificial discs at L4-5. Each implanted model was subjected to a combination of 400 N follower load and 5 Nm of flexion/extension moments. ABAQUS version 6.5 (ABAQUS Inc., Providence, RI, USA) and FEMAP version 8.20 (Electronic Data Systems Corp., Plano, TX, USA) were used for meshing and analysis of geometry of the intact and implanted models. Under the flexion load, the intersegmental rotation angles of all the implanted models were similar to that of the intact model, but under the extension load, the values were greater than that of the intact model. The facet contact loads of three implanted models were greater than the loads observed with the intact model. Under the flexion load, three types of the implanted model at the L4-5 level showed the intersegmental rotation angle similar to the one measured with the intact model. Under the extension load, all of the artificial disc implanted models demonstrated an increased extension rotational angle at the operated level (L4-5), resulting in an increase under the facet contact load when compared with the adjacent segments. The increased facet load may lead to facet degeneration.

  1. Biomechanical Changes of the Lumbar Segment after Total Disc Replacement : Charite®, Prodisc® and Maverick® Using Finite Element Model Study

    PubMed Central

    Kim, Ki-Tack; Lee, Sang-Hun; Suk, Kyung-Soo; Lee, Jung-Hee

    2010-01-01

    Objective The purpose of this study was to analyze the biomechanical effects of three different constrained types of an artificial disc on the implanted and adjacent segments in the lumbar spine using a finite element model (FEM). Methods The created intact model was validated by comparing the flexion-extension response without pre-load with the corresponding results obtained from the published experimental studies. The validated intact lumbar model was tested after implantation of three artificial discs at L4-5. Each implanted model was subjected to a combination of 400 N follower load and 5 Nm of flexion/extension moments. ABAQUS™ version 6.5 (ABAQUS Inc., Providence, RI, USA) and FEMAP version 8.20 (Electronic Data Systems Corp., Plano, TX, USA) were used for meshing and analysis of geometry of the intact and implanted models. Results Under the flexion load, the intersegmental rotation angles of all the implanted models were similar to that of the intact model, but under the extension load, the values were greater than that of the intact model. The facet contact loads of three implanted models were greater than the loads observed with the intact model. Conclusion Under the flexion load, three types of the implanted model at the L4-5 level showed the intersegmental rotation angle similar to the one measured with the intact model. Under the extension load, all of the artificial disc implanted models demonstrated an increased extension rotational angle at the operated level (L4-5), resulting in an increase under the facet contact load when compared with the adjacent segments. The increased facet load may lead to facet degeneration. PMID:20617091

  2. Relativistic Disc Line: A Tool to Constrain Neutron Star Equation of State Models

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, Sudip

    2017-09-01

    Relativistic iron Kα spectral emission line from the inner disc of a neutron star Low-Mass X-ray Binary (LMXB) was first detected in 2007. This discovery opened up new ways to probe strong gravity and dense matter. The past decade has seen detections of such a line from many neutron star LMXBs, and confirmation of this line from the same source with several X-ray satellites. These have firmly established the new field of relativistic disc line from neutron star systems in only a decade or so. Fitting the shape of such a line with an appropriate general relativistic model provides the accretion disc inner edge radius to the stellar mass ratio. In this review, we briefly discuss how an accurate measurement of this ratio with a future larger area X-ray instrument can be used to constrain neutron star equation of state models.

  3. In vivo dynamic stiffness of the porcine lumbar spine exposed to cyclic loading: influence of load and degeneration.

    PubMed

    Kaigle, A; Ekström, L; Holm, S; Rostedt, M; Hansson, T

    1998-02-01

    The dynamic axial stiffness of the L2-3 motion segment subjected to vibratory loading under intact and injured states of the intervertebral disc was studied using an in vivo porcine model. Three groups of animals with the following states of the intervertebral discs were studied: intact disc, acutely injured disc, and degenerated disc. A miniaturized servo-hydraulic exciter was used to sinusoidally vibrate the motion segment from 0.05 to 25 Hz under a compressive load with a peak value of either 100 or 200 N. The dynamic axial stiffness of the intervertebral disc was calculated at 1-Hz intervals over the frequency range. The results showed that the dynamic axial stiffness was frequency dependent. A positive relationship was found between an increase in mean dynamic stiffness and load magnitude. An increase in mean stiffness with successive exposures at the same load magnitude was observed, despite the allowance of a recovery period between loading. The greatest difference was noted between the first and second load sets. No significant change in stiffness was found due to an acute disc injury, whereas a significant increase in mean stiffness was found for the degenerated disc group as compared with the intact group. The form of the frequency response curve, however, remained relatively unaltered regardless of the degenerated state of the disc. With heavier loads, repeated loading, and/or disc degeneration, the stiffness of the intervertebral disc increases. An increase in stiffness can mean a reduction in the amount of allowable motion within the motion segment or a potentially harmful increase in force to obtain the desired motion. This may locally result in greater stresses due to an altered ability of the disc to distribute loads.

  4. Investigation of intervertebral disc degeneration using multivariate FTIR spectroscopic imaging† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5fd00160a Click here for additional data file.

    PubMed Central

    Peeters, Mirte; Detiger, Suzanne E. L.; Helder, Marco N.; Smit, Theo H.; Le Maitre, Christine L.; Sammon, Chris

    2016-01-01

    Traditionally tissue samples are analysed using protein or enzyme specific stains on serial sections to build up a picture of the distribution of components contained within them. In this study we investigated the potential of multivariate curve resolution-alternating least squares (MCR-ALS) to deconvolute 2nd derivative spectra of Fourier transform infrared (FTIR) microscopic images measured in transflectance mode of goat and human paraffin embedded intervertebral disc (IVD) tissue sections, to see if this methodology can provide analogous information to that provided by immunohistochemical stains and bioassays but from a single section. MCR-ALS analysis of non-degenerate and enzymatically in vivo degenerated goat IVDs reveals five matrix components displaying distribution maps matching histological stains for collagen, elastin and proteoglycan (PG), as well as immunohistochemical stains for collagen type I and II. Interestingly, two components exhibiting characteristic spectral and distribution profiles of proteoglycans were found, and relative component/tissue maps of these components (labelled PG1 and PG2) showed distinct distributions in non-degenerate versus mildly degenerate goat samples. MCR-ALS analysis of human IVD sections resulted in comparable spectral profiles to those observed in the goat samples, highlighting the inter species transferability of the presented methodology. Multivariate FTIR image analysis of a set of 43 goat IVD sections allowed the extraction of semi-quantitative information from component/tissue gradients taken across the IVD width of collagen type I, collagen type II, PG1 and PG2. Regional component/tissue parameters were calculated and significant correlations were found between histological grades of degeneration and PG parameters (PG1: p = 0.0003, PG2: p < 0.0001); glycosaminoglycan (GAG) content and PGs (PG1: p = 0.0055, PG2: p = 0.0001); and MRI T2* measurements and PGs (PG1: p = 0.0021, PG2: p < 0.0001). Additionally

  5. A 1-D model of the nonlinear dynamics of the human lumbar intervertebral disc

    NASA Astrophysics Data System (ADS)

    Marini, Giacomo; Huber, Gerd; Püschel, Klaus; Ferguson, Stephen J.

    2017-01-01

    Lumped parameter models of the spine have been developed to investigate its response to whole body vibration. However, these models assume the behaviour of the intervertebral disc to be linear-elastic. Recently, the authors have reported on the nonlinear dynamic behaviour of the human lumbar intervertebral disc. This response was shown to be dependent on the applied preload and amplitude of the stimuli. However, the mechanical properties of a standard linear elastic model are not dependent on the current deformation state of the system. The aim of this study was therefore to develop a model that is able to describe the axial, nonlinear quasi-static response and to predict the nonlinear dynamic characteristics of the disc. The ability to adapt the model to an individual disc's response was a specific focus of the study, with model validation performed against prior experimental data. The influence of the numerical parameters used in the simulations was investigated. The developed model exhibited an axial quasi-static and dynamic response, which agreed well with the corresponding experiments. However, the model needs further improvement to capture additional peculiar characteristics of the system dynamics, such as the change of mean point of oscillation exhibited by the specimens when oscillating in the region of nonlinear resonance. Reference time steps were identified for specific integration scheme. The study has demonstrated that taking into account the nonlinear-elastic behaviour typical of the intervertebral disc results in a predicted system oscillation much closer to the physiological response than that provided by linear-elastic models. For dynamic analysis, the use of standard linear-elastic models should be avoided, or restricted to study cases where the amplitude of the stimuli is relatively small.

  6. The effect of sustained compression on oxygen metabolic transport in the intervertebral disc decreases with degenerative changes.

    PubMed

    Malandrino, Andrea; Noailly, Jérôme; Lacroix, Damien

    2011-08-01

    Intervertebral disc metabolic transport is essential to the functional spine and provides the cells with the nutrients necessary to tissue maintenance. Disc degenerative changes alter the tissue mechanics, but interactions between mechanical loading and disc transport are still an open issue. A poromechanical finite element model of the human disc was coupled with oxygen and lactate transport models. Deformations and fluid flow were linked to transport predictions by including strain-dependent diffusion and advection. The two solute transport models were also coupled to account for cell metabolism. With this approach, the relevance of metabolic and mechano-transport couplings were assessed in the healthy disc under loading-recovery daily compression. Disc height, cell density and material degenerative changes were parametrically simulated to study their influence on the calculated solute concentrations. The effects of load frequency and amplitude were also studied in the healthy disc by considering short periods of cyclic compression. Results indicate that external loads influence the oxygen and lactate regional distributions within the disc when large volume changes modify diffusion distances and diffusivities, especially when healthy disc properties are simulated. Advection was negligible under both sustained and cyclic compression. Simulating degeneration, mechanical changes inhibited the mechanical effect on transport while disc height, fluid content, nucleus pressure and overall cell density reductions affected significantly transport predictions. For the healthy disc, nutrient concentration patterns depended mostly on the time of sustained compression and recovery. The relevant effect of cell density on the metabolic transport indicates the disturbance of cell number as a possible onset for disc degeneration via alteration of the metabolic balance. Results also suggest that healthy disc properties have a positive effect of loading on metabolic transport. Such

  7. Molecular Mechanisms of Biological Aging in Intervertebral Discs

    PubMed Central

    Vo, Nam V.; Hartman, Robert A.; Patil, Prashanti R.; Risbud, Makarand V.; Kletsas, Dimitris; Iatridis, James C.; Hoyland, Judith A.; Le Maitre, Christine L.; Sowa, Gwendolyn A.; Kang, James D.

    2016-01-01

    Advanced age is the greatest risk factor for the majority of human ailments, including spine-related chronic disability and back pain, which stem from age-associated intervertebral disc degeneration (IDD). Given the rapid global rise in the aging population, understanding the biology of intervertebral disc aging in order to develop effective therapeutic interventions to combat the adverse effects of aging on disc health is now imperative. Fortunately, recent advances in aging research have begun to shed light on the basic biological process of aging. Here we review some of these insights and organize the complex process of disc aging into three different phases to guide research efforts to understand the biology of disc aging. The objective of this review is to provide an overview of the current knowledge and the recent progress made to elucidate specific molecular mechanisms underlying disc aging. In particular, studies over the last few years have uncovered cellular senescence and genomic instability as important drivers of disc aging. Supporting evidence comes from DNA repair-deficient animal models that show increased disc cellular senescence and accelerated disc aging. Additionally, stress-induced senescent cells have now been well documented to secrete catabolic factors, which can negatively impact the physiology of neighboring cells and ECM. These along with other molecular drivers of aging are reviewed in depth to shed crucial insights into the underlying mechanisms of age-related disc degeneration. We also highlight molecular targets for novel therapies and emerging candidate therapeutics that may mitigate age-associated IDD. PMID:26890203

  8. Stress Analysis of Anterior-Disc-Displaced Temporomandibular Joint Using Individual Finite Element Model

    NASA Astrophysics Data System (ADS)

    Tanaka, Masao; Tanaka, Eiji; Todoh, Masahiro; Asai, Daisuke; Kuroda, Yukiko

    Temporomandibular joint (TMJ) disorder relates to the biomechanical irregularity of the structual joint components, and the behavior of soft tissue components is considered as a key to understand the biomechanical condition in the TMJ. The configuration of joint components, however, closely depends on individual patients. In this study, attention has been focused on the stress and displacement of irregular TMJs with anterior disc displacement. Using biplane magnetic resonance (MR) images, typical anterior-disc-displaced (ADD) TMJ of a patient with temporomandibular disorder has been modeled individually. The stress distribution in ADD TMJs has been compared with that in normal TMJs. Parameter studies with the elastic modulus have been carried out and it revealed that the stress distribution in the TMJ is highly dependent on the connective tissue modulus as well as disc modulus in the case of ADD TMJ, and that the disc displacement due to mouth opening movement depends on disc modulus in normal TMJ but depends on retrodiscal connective tissue in ADD TMJ.

  9. Dippers and dusty disc edges: new diagnostics and comparison to model predictions

    NASA Astrophysics Data System (ADS)

    Bodman, Eva H. L.; Quillen, Alice C.; Ansdell, Megan; Hippke, Michael; Boyajian, Tabetha S.; Mamajek, Eric E.; Blackman, Eric G.; Rizzuto, Aaron; Kastner, Joel H.

    2017-09-01

    We revisit the nature of large dips in flux from extinction by dusty circumstellar material that is observed by Kepler for many young stars in the Upper Sco and ρ Oph star formation regions. These young, low-mass 'dipper' stars are known to have low accretion rates and primarily host moderately evolved dusty circumstellar discs. Young low-mass stars often exhibit rotating starspots that cause quasi-periodic photometric variations. We found no evidence for periods associated with the dips that are different from the starspot rotation period in spectrograms constructed from the light curves. The material causing the dips in most of these light curves must be approximately corotating with the star. We find that disc temperatures computed at the disc corotation radius are cool enough that dust should not sublime. Crude estimates for stellar magnetic field strengths and accretion rates are consistent with magnetospheric truncation near the corotation radius. Magnetospheric truncation models can explain why the dips are associated with material near corotation and how dusty material is lifted out of the mid-plane to obscure the star that would account for the large fraction of young low-mass stars that are dippers. We propose that variations in disc orientation angle, stellar magnetic field dipole tilt axis and disc accretion rate are underlying parameters accounting for differences in the dipper light curves.

  10. MODELING NIGROSTRIATAL DEGENERATION IN ORGANOTYPIC CULTURES, A NEW EX VIVO MODEL OF PARKINSON’S DISEASE

    PubMed Central

    DAVIAUD, N.; GARBAYO, E.; LAUTRAM, N.; FRANCONI, F.; LEMAIRE, L.; PEREZ-PINZON, M.; MONTERO-MENEI, C. N.

    2014-01-01

    Parkinson’s disease (PD) is the second most frequent neurodegenerative disorder afflicting 2% of the population older than 65 years worldwide. Recently, brain organotypic slices have been used to model neurodegenerative disorders, including PD. They conserve brain three-dimensional architecture, synaptic connectivity and its microenvironment. This model has allowed researchers a simple and rapid method to observe cellular interactions and mechanisms. In the present study, we developed an organotypic PD model from rat brains that includes all the areas involved in the nigrostriatal pathway in a single slice preparation, without using neurotoxins to induce the dopaminergic lesion. The mechanical transection of the nigrostriatal pathway obtained during slice preparation induced PD-like histopathology. Progressive nigrostriatal degeneration was monitored combining innovative approaches, such as diffusion tensor magnetic resonance imaging (DT-RMI) to follow fiber degeneration and mass spectrometry to quantify striatal dopamine content, together with bright-field and fluorescence microscopy imaging. A substantia nigra dopaminergic cell number decrease was observed by immunohistochemistry against rat tyrosine hydroxylase (TH) reaching 80% after 2 days in culture associated with a 30% decrease of striatal TH-positive fiber density, a 15% loss of striatal dopamine content quantified by mass spectrometry and a 70% reduction of nigrostriatal fiber fractional anisotropy quantified by DT-RMI. In addition, a significant decline of medium spiny neuron density was observed from days 7 to 16. These sagittal organotypic slices could be used to study the early stage of PD, namely dopaminergic degeneration, and the late stage of the pathology with dopaminergic and GABAergic neuron loss. This novel model might improve the understanding of PD and may represent a promising tool to refine the evaluation of new therapeutic approaches. PMID:24161279

  11. Loss of Ikbkap Causes Slow, Progressive Retinal Degeneration in a Mouse Model of Familial Dysautonomia.

    PubMed

    Ueki, Yumi; Ramirez, Grisela; Salcedo, Ernesto; Stabio, Maureen E; Lefcort, Frances

    2016-01-01

    Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy that is caused by a mutation in the gene for inhibitor of kappa B kinase complex-associated protein (IKBKAP). Although FD patients suffer from multiple neuropathies, a major debilitation that affects their quality of life is progressive blindness. To determine the requirement for Ikbkap in the developing and adult retina, we generated Ikbkap conditional knockout (CKO) mice using a TUBA1a promoter-Cre (Tα1-Cre). In the retina, Tα1-Cre expression is detected predominantly in retinal ganglion cells (RGCs). At 6 months, significant loss of RGCs had occurred in the CKO retinas, with the greatest loss in the temporal retina, which is the same spatial phenotype observed in FD, Leber hereditary optic neuropathy, and dominant optic atrophy. Interestingly, the melanopsin-positive RGCs were resistant to degeneration. By 9 months, signs of photoreceptor degeneration were observed, which later progressed to panretinal degeneration, including RGC and photoreceptor loss, optic nerve thinning, Müller glial activation, and disruption of layers. Taking these results together, we conclude that although Ikbkap is not required for normal development of RGCs, its loss causes a slow, progressive RGC degeneration most severely in the temporal retina, which is later followed by indirect photoreceptor loss and complete retinal disorganization. This mouse model of FD is not only useful for identifying the mechanisms mediating retinal degeneration, but also provides a model system in which to attempt to test therapeutics that may mitigate the loss of vision in FD patients.

  12. Evaluation of load transfer characteristics of a dynamic stabilization device on disc loading under compression.

    PubMed

    Zhang, Qing Hang; Zhou, Yuan Li; Petit, Dominique; Teo, Ee Chon

    2009-06-01

    In the current study, finite element analyses were conducted to examine the biomechanical capability of a newly design dynamic stabilization system, FlexPLUS, to restore the load transmission of degenerated intervertebral L4-L5 lumbar motion segment spine under compression. Detailed three-dimensional FE models of L4-L5 motion segment and the FlexPLUS were developed. Compressive loading up to 1000N was applied to the intact L4-L5 model, the L4-L5 models with slight and moderate degenerated disc, and the implanted L4-L5 model. Further more, the load transmission characteristics of Dynesys and a rigid rod was also simulated for comparison. The resultant load-displacement curves and the load transferred through annulus under various conditions were compared. The predicted axial displacement of L4 top surface against applied compressive force of the intact L4-L5 model agreed well with experimental data. The predicted results showed that degenerated disc has significant effect on the lumbar segment load bearing capacity. Not only the stiffness of the segment was greatly increased, the uniform nature of the disc stress distribution was also altered. The FlexPLUS can effectively reduce the disc loading of degenerated model. Although the non-uniform load distribution pattern through annulus was not improved, the overall stress magnitude was greatly reduced to the level of intact model for grade II degeneration.

  13. Mechanical testing and modelling of carbon-carbon composites for aircraft disc brakes

    NASA Astrophysics Data System (ADS)

    Bradley, Luke R.

    The objective of this study is to improve the understanding of the stress distributions and failure mechanisms experienced by carbon-carbon composite aircraft brake discs using finite element (FE) analyses. The project has been carried out in association with Dunlop Aerospace as an EPSRC CASE studentship. It therefore focuses on the carbon-carbon composite brake disc material produced by Dunlop Aerospace, although it is envisaged that the approach will have broader applications for modelling and mechanical testing of carbon-carbon composites in general. The disc brake material is a laminated carbon-carbon composite comprised of poly(acrylonitrile) (PAN) derived carbon fibres in a chemical vapour infiltration (CVI) deposited matrix, in which the reinforcement is present in both continuous fibre and chopped fibre forms. To pave the way for the finite element analysis, a comprehensive study of the mechanical properties of the carbon-carbon composite material was carried out. This focused largely, but not entirely, on model composite materials formulated using structural elements of the disc brake material. The strengths and moduli of these materials were measured in tension, compression and shear in several orientations. It was found that the stress-strain behaviour of the materials were linear in directions where there was some continuous fibre reinforcement, but non-linear when this was not the case. In all orientations, some degree of non-linearity was observed in the shear stress-strain response of the materials. However, this non-linearity was generally not large enough to pose a problem for the estimation of elastic moduli. Evidence was found for negative Poisson's ratio behaviour in some orientations of the material in tension. Additionally, the through-thickness properties of the composite, including interlaminar shear strength, were shown to be positively related to bulk density. The in-plane properties were mostly unrelated to bulk density over the range of

  14. A Model of the Spatio-temporal Dynamics of Drosophila Eye Disc Development.

    PubMed

    Fried, Patrick; Sánchez-Aragón, Máximo; Aguilar-Hidalgo, Daniel; Lehtinen, Birgitta; Casares, Fernando; Iber, Dagmar

    2016-09-01

    Patterning and growth are linked during early development and have to be tightly controlled to result in a functional tissue or organ. During the development of the Drosophila eye, this linkage is particularly clear: the growth of the eye primordium mainly results from proliferating cells ahead of the morphogenetic furrow (MF), a moving signaling wave that sweeps across the tissue from the posterior to the anterior side, that induces proliferating cells anterior to it to differentiate and become cell cycle quiescent in its wake. Therefore, final eye disc size depends on the proliferation rate of undifferentiated cells and on the speed with which the MF sweeps across the eye disc. We developed a spatio-temporal model of the growing eye disc based on the regulatory interactions controlled by the signals Decapentaplegic (Dpp), Hedgehog (Hh) and the transcription factor Homothorax (Hth) and explored how the signaling patterns affect the movement of the MF and impact on eye disc growth. We used published and new quantitative data to parameterize the model. In particular, two crucial parameter values, the degradation rate of Hth and the diffusion coefficient of Hh, were measured. The model is able to reproduce the linear movement of the MF and the termination of growth of the primordium. We further show that the model can explain several mutant phenotypes, but fails to reproduce the previously observed scaling of the Dpp gradient in the anterior compartment.

  15. TTK Chitra tilting disc heart valve model TC2: An assessment of fatigue life and durability.

    PubMed

    Subhash, N N; Rajeev, Adathala; Sujesh, Sreedharan; Muraleedharan, C V

    2017-08-01

    Average age group of heart valve replacement in India and most of the Third World countries is below 30 years. Hence, the valve for such patients need to be designed to have a service life of 50 years or more which corresponds to 2000 million cycles of operation. The purpose of this study was to assess the structural performance of the TTK Chitra tilting disc heart valve model TC2 and thereby address its durability. The TC2 model tilting disc heart valves were assessed to evaluate the risks connected with potential structural failure modes. To be more specific, the studies covered the finite element analysis-based fatigue life prediction and accelerated durability testing of the tilting disc heart valves for nine different valve sizes. First, finite element analysis-based fatigue life prediction showed that all nine valve sizes were in the infinite life region. Second, accelerated durability test showed that all nine valve sizes remained functional for 400 million cycles under experimental conditions. The study ensures the continued function of TC2 model tilting disc heart valves over duration in excess of 50 years. The results imply that the TC2 model valve designs are structurally safe, reliable and durable.

  16. Analytical model of electron transport in polycrystalline, degenerately doped ZnO films

    SciTech Connect

    Bikowski, André Ellmer, Klaus

    2014-10-14

    An analytical description of the charge carrier transport, valid for non-degenerated and degenerated semiconductors, was developed, critically reviewed, and fitted to the temperature-dependent Hall mobility data of magnetron sputtered, degenerately doped ZnO:Al films. Our extended model for grain boundary scattering in semiconductors of arbitrary degeneracy is based on previous models from literature and suitable to describe the Hall mobility of the carriers as a function of the free carrier concentration and the temperature at the same time. It is mathematically simple enough for a fast fit procedure, which is not possible with most of the previous models. Applying a combined transport model consisting of ionized impurity scattering, phonon scattering, and grain boundary scattering in degenerate semiconductors, we were able to determine the trap density at the grain boundaries Nₜ ≈ 3×10¹³ to 5×10¹³cm⁻² and the deformation potential E{sub ac} in the range of 5 eV to 9 eV depending on the details of the transport model.

  17. Rat disc torsional mechanics: effect of lumbar and caudal levels and axial compression load.

    PubMed

    Espinoza Orías, Alejandro A; Malhotra, Neil R; Elliott, Dawn M

    2009-03-01

    Rat models with altered loading are used to study disc degeneration and mechano-transduction. Given the prominent role of mechanics in disc function and degeneration, it is critical to measure mechanical behavior to evaluate changes after model interventions. Axial compression mechanics of the rat disc are representative of the human disc when normalized by geometry, and differences between the lumbar and caudal disc have been quantified in axial compression. No study has quantified rat disc torsional mechanics. Compare the torsional mechanical behavior of rat lumbar and caudal discs, determine the contribution of combined axial load on torsional mechanics, and compare the torsional properties of rat discs to human lumbar discs. Cadaveric biomechanical study. Cyclic torsion without compressive load followed by cyclic torsion with a fixed compressive load was applied to rat lumbar and caudal disc levels. The apparent torsional modulus was higher in the lumbar region than in the caudal region: 0.081+/-0.026 (MPa/degrees, mean+/-SD) for lumbar axially loaded; 0.066+/-0.028 for caudal axially loaded; 0.091+/-0.033 for lumbar in pure torsion; and 0.056+/-0.035 for caudal in pure torsion. These values were similar to human disc properties reported in the literature ranging from 0.024 to 0.21 MPa/degrees. Use of the caudal disc as a model may be appropriate if the mechanical focus is within the linear region of the loading regime. These results provide support for use of this animal model in basic science studies with respect to torsional mechanics.

  18. Continuum and line modelling of discs around young stars. II. Line diagnostics for GASPS from the DENT grid

    NASA Astrophysics Data System (ADS)

    Kamp, I.; Woitke, P.; Pinte, C.; Tilling, I.; Thi, W.-F.; Menard, F.; Duchene, G.; Augereau, J.-C.

    2011-08-01

    Aims: We want to understand the chemistry and physics of discs on the basis of a large unbiased and statistically relevant grid of disc models. One of the main goals is to explore the diagnostic power of various gas emission lines and line ratios for deriving main disc parameters such as the gas mass. Methods: We explored the results of the DENT grid (Disk Evolution with Neat Theory) that consists of 300 000 disc models with 11 free parameters. Through a statistical analysis, we searched for correlations and trends in an effort to find tools for disc diagnostic. Results: All calculated quantities like species masses, temperatures, continuum, and line fluxes differ by several orders of magnitude across the entire parameter space. The broad distribution of these quantities as a function of input parameters shows the limitation of using a prototype T Tauri or Herbig Ae/Be disc model. The statistical analysis of the DENT grid shows that CO gas is rarely the dominant carbon reservoir in discs. Models with large inner radii (10 times the dust condensation radius) and/or shallow surface density gradients lack massive gas-phase water reservoirs. Also, 60% of the discs have gas temperatures averaged over the oxygen mass in the range between 15 and 70 K; the average gas temperatures for CO and O differ by less than a factor two. Our study of the observational diagnostics shows that the [C ii] 158 μm fine structure line flux is very sensitive to the stellar UV flux and presence of a UV excess, and that it traces the outer disc radius (Rout). In the submm, the CO low J rotational lines also trace Rout. Low [O i] 63/145 line ratios (disc models without UV excess. A combination of the [O i] 63 line and low J CO lines correlates with several disc properties, such as the average O i gas temperature in

  19. Mycobacterium leprae-induced demyelination: a model for early nerve degeneration.

    PubMed

    Rambukkana, Anura

    2004-08-01

    The molecular events that occur at the early phase of many demyelinating neurodegenerative diseases are unknown. A recent demonstration of rapid demyelination and axonal injury induced by Mycobacterium leprae provides a model for elucidating the molecular events of early nerve degeneration which might be common to neurodegenerative diseases of both infectious origin and unknown etiology. The identification of the M. leprae-targeted Schwann cell receptor, dystroglycan, and its associated molecules in myelination, demyelination and axonal functions suggests a role for these molecules in early nerve degeneration.

  20. Independent degeneration of photoreceptors and retinal pigment epithelium in conditional knockout mouse models of choroideremia

    PubMed Central

    Tolmachova, Tanya; Anders, Ross; Abrink, Magnus; Bugeon, Laurence; Dallman, Margaret J.; Futter, Clare E.; Ramalho, José S.; Tonagel, Felix; Tanimoto, Naoyuki; Seeliger, Mathias W.; Huxley, Clare; Seabra, Miguel C.

    2006-01-01

    Choroideremia (CHM) is an X-linked degeneration of the retinal pigment epithelium (RPE), photoreceptors, and choroid, caused by loss of function of the CHM/REP1 gene. REP1 is involved in lipid modification (prenylation) of Rab GTPases, key regulators of intracellular vesicular transport and organelle dynamics. To study the pathogenesis of CHM and to develop a model for assessing gene therapy, we have created a conditional mouse knockout of the Chm gene. Heterozygous-null females exhibit characteristic hallmarks of CHM: progressive degeneration of the photoreceptors, patchy depigmentation of the RPE, and Rab prenylation defects. Using tamoxifen-inducible and tissue-specific Cre expression in combination with floxed Chm alleles, we show that CHM pathogenesis involves independently triggered degeneration of photoreceptors and the RPE, associated with different subsets of defective Rabs. PMID:16410831

  1. ICT and e-Governance: A Conceptual Model of e-DISC

    NASA Astrophysics Data System (ADS)

    Tejasvee, Sanjay; Sarangdevot, S. S.; Gahlot, Devendra; Gour, Vishal; Sandal, Shruti

    2010-11-01

    One of the most important objectives of e-governance is, proper distribution and delivery of government information and services to the citizens. By progression in resources of information technology, great opportunities comes to the government for serve information and services to the citizens and public sector in better manner. This paper intends to examine and explore the conceptual model of e-DISC (Effective Deliverance of Information and Services to the Citizens) The purpose of this paper is to gain a better understanding of e-government in India with the concept of e-DISC with ICTs and how to deal with challenges and barriers for successful e-DISC model with accuracy. The obtained results prove that the utilizing and by increasing interest in the new electronic, information, and communication technologies (ICTs) and e-DISC model in recent time, government improved the quality of e-governance and delivery of information and services and acknowledged the awareness of the system is also valuable.

  2. Parametric T2 and T2* mapping techniques to visualize intervertebral disc degeneration in patients with low back pain: initial results on the clinical use of 3.0 Tesla MRI.

    PubMed

    Welsch, Goetz Hannes; Trattnig, Siegfried; Paternostro-Sluga, Tatjana; Bohndorf, Klaus; Goed, Sabine; Stelzeneder, David; Mamisch, Tallal Charles

    2011-05-01

    To assess, compare and correlate quantitative T2 and T2* relaxation time measurements of intervertebral discs (IVDs) in patients suffering from low back pain, with respect to the IVD degeneration as assessed by the morphological Pfirrmann Score. Special focus was on the spatial variation of T2 and T2* between the annulus fibrosus (AF) and the nucleus pulposus (NP). Thirty patients (mean age: 38.1 ± 9.1 years; 20 female, 10 male) suffering from low back pain were included. Morphological (sagittal T1-FSE, sagittal and axial T2-FSE) and biochemical (sagittal T2- and T2* mapping) MRI was performed at 3 Tesla covering IVDs L1-L2 to L5-S1. All IVDs were morphologically classified using the Pfirrmann score. Region-of-interest (ROI) analysis was performed on midsagittal T2 and T2* maps at five ROIs from anterior to posterior to obtain information on spatial variation between the AF and the NP. Statistical analysis-of-variance and Pearson correlation was performed. The spatial variation as an increase in T2 and T2* values from the AF to the NP was highest at Pfirmann grade I and declined at higher Pfirmann grades II-IV (p < 0.05). With increased IVD degeneration, T2 and T2* revealed a clear differences in the NP, whereas T2* was additionally able to depict changes in the posterior AF. Correlation between T2 and T2* showed a medium Pearson's correlation (0.210 to 0.356 [p < 0.001]). The clear differentiation of IVD degeneration and the possible quantification by means of T2 and fast T2* mapping may provide a new tool for follow-up therapy protocols in patients with low back pain.

  3. Influence of high-permeability discs in an axisymmetric model of the Cadarache dynamo experiment

    NASA Astrophysics Data System (ADS)

    Giesecke, A.; Nore, C.; Stefani, F.; Gerbeth, G.; Léorat, J.; Herreman, W.; Luddens, F.; Guermond, J.-L.

    2012-05-01

    Numerical simulations of the kinematic induction equation are performed on a model configuration of the Cadarache von-Kármán-sodium dynamo experiment. The effect of a localized axisymmetric distribution of relative permeability μr that represents soft iron material within the conducting fluid flow is investigated. The critical magnetic Reynolds number Rmc for dynamo action of the first non-axisymmetric mode roughly scales like Rmcμr - Rmc∞∝μ-1/2r, i.e. the threshold decreases as μr increases. This scaling law suggests a skin effect mechanism in the soft iron discs. More important with regard to the Cadarache dynamo experiment, we observe a purely toroidal axisymmetric mode localized in the high-permeability discs which becomes dominant for large μr. In this limit, the toroidal mode is close to the onset of dynamo action with a (negative) growth rate that is rather independent of the magnetic Reynolds number. We qualitatively explain this effect by paramagnetic pumping at the fluid/disc interface and propose a simplified model that quantitatively reproduces numerical results. The crucial role of the high-permeability discs in the mode selection in the Cadarache dynamo experiment cannot be inferred from computations using idealized pseudo-vacuum boundary conditions (H × n = 0).

  4. A predictive model for disability in patients with lumbar disc herniation.

    PubMed

    Chen, Hsin-Ni; Tsai, Yun-Fang

    2013-03-01

    Lumbar disc herniation may influence patients' daily activities and social interactions; however, no predictive models of disability could be found for patients with lumbar disc herniation. We aimed to explore predictive factors for disability in patients with lumbar disc herniation. The sample included 216 patients recruited from the orthopedic outpatient clinics at a medical center in northern Taiwan. Data were collected on patients' pain, fatigue, depression, disability, and demographics. Hierarchical multiple regression analysis was used in model verification. Path analysis was used to investigate causal relationships between disability and other factors. In path analysis, the most influential factor affecting the disability level was the pain level (standardized regression coefficient, b = 0.746), followed by the fatigue level (b = 0.138) and depression level (b = 0.100). The depression level was directly affected by the fatigue level (b = 0.416) and the pain level (b = 0.367), the fatigue level was directly affected by the pain level (b = 0.538), and the pain level was directly affected by age (b = 0.140) and previous surgery (b = 0.260). We recommend that health-care providers regularly assess and treat pain and depression to reduce/prevent disability among patients with lumbar disc herniation, even among those who are apparently functioning well in the community.

  5. Disc cell therapies: critical issues.

    PubMed

    Tibiletti, Marta; Kregar Velikonja, Nevenka; Urban, Jill P G; Fairbank, Jeremy C T

    2014-06-01

    Disc cell therapies, in which cells are injected into the degenerate disc in order to regenerate the matrix and restore function, appear to be an attractive, minimally invasive method of treatment. Interest in this area has stimulated research into disc cell biology in particular. However, other important issues, some of which are discussed here, need to be considered if cell-based therapies are to be brought to the clinic. Firstly, a question which is barely addressed in the literature, is how to identify patients with 'degenerative disc disease' who would benefit from cell therapy. Pain not disc degeneration is the symptom which drives patients to the clinic. Even though there are associations between back pain and disc degeneration, many people with even severely degenerate discs, with herniated discs or with spinal stenosis, are pain-free. It is not possible using currently available techniques to identify whether disc repair or regeneration would remove symptoms or prevent symptoms from occurring in future. Moreover, the repair process in human discs is very slow (years) because of the low cell density which can be supported nutritionally even in healthy human discs. If repair is necessary for relief of symptoms, questions regarding quality of life and rehabilitation during this long process need consideration. Also, some serious technical issues remain. Finding appropriate cell sources and scaffolds have received most attention, but these are not the only issues determining the feasibility of the procedure. There are questions regarding the safety of implanting cells by injection through the annulus whether the nutrient supply to the disc is sufficient to support implanted cells and whether, if cells are able to survive, conditions in a degenerate human disc will allow them to repair the damaged tissue. If cell therapy for treatment of disc-related disorders is to enter the clinic as a routine treatment, investigations must examine the questions related to

  6. Linear moose model with pairs of degenerate gauge boson triplets

    NASA Astrophysics Data System (ADS)

    Casalbuoni, Roberto; Coradeschi, Francesco; de Curtis, Stefania; Dominici, Daniele

    2008-05-01

    The possibility of a strongly interacting electroweak symmetry breaking sector, as opposed to the weakly interacting light Higgs of the standard model, is not yet ruled out by experiments. In this paper we make an extensive study of a deconstructed model (or “moose” model) providing an effective description of such a strong symmetry breaking sector, and show its compatibility with experimental data for a wide portion of the model parameter space. The model is a direct generalization of the previously proposed D-BESS model.

  7. Linear moose model with pairs of degenerate gauge boson triplets

    SciTech Connect

    Casalbuoni, Roberto; Coradeschi, Francesco; De Curtis, Stefania; Dominici, Daniele

    2008-05-01

    The possibility of a strongly interacting electroweak symmetry breaking sector, as opposed to the weakly interacting light Higgs of the standard model, is not yet ruled out by experiments. In this paper we make an extensive study of a deconstructed model (or ''moose'' model) providing an effective description of such a strong symmetry breaking sector, and show its compatibility with experimental data for a wide portion of the model parameter space. The model is a direct generalization of the previously proposed D-BESS model.

  8. Evaluation of cartilage degeneration in a rat model of rotator cuff tear arthropathy.

    PubMed

    Kramer, Erik J; Bodendorfer, Blake M; Laron, Dominique; Wong, Jason; Kim, Hubert T; Liu, Xuhui; Feeley, Brian T

    2013-12-01

    Rotator cuff tears are the most common injury seen by shoulder surgeons. Glenohumeral osteoarthritis develops in many late-stage rotator cuff tear patients as a result of torn cuff tendons, termed "cuff tear arthropathy." However, the mechanisms of cuff tear arthropathy have not been fully established. It has been hypothesized that a combination of synovial and mechanical factors contribute equally to the development of cuff tear arthropathy. The goal of this study was to assess the utility of this model in investigating cuff tear arthropathy. We used a rat model that accurately reflects rotator cuff muscle degradation after massive rotator cuff tears through either infraspinatus and supraspinatus tenotomy or suprascapular nerve transection. Using a modified Mankin scoring system, we found significant glenohumeral cartilage damage after both rotator cuff tenotomy and suprascapular nerve transection after only 12 weeks. Cartilage degeneration was similar between groups and was present on both the humeral head and the glenoid. Denervation of the supraspinatus and infraspinatus muscles without opening the joint capsule caused cartilage degeneration similar to that found in the tendon transection group. Our results suggest that altered mechanical loading after rotator cuff tears is the primary factor in cartilage degeneration after rotator cuff tears. Clinically, understanding the process of cartilage degeneration after rotator cuff injury will help guide treatment decisions in the setting of rotator cuff tears. Basic science study, animal model. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  9. A self-consistent model for the evolution of the gas produced in the debris disc of β Pictoris

    NASA Astrophysics Data System (ADS)

    Kral, Q.; Wyatt, M.; Carswell, R. F.; Pringle, J. E.; Matrà, L.; Juhász, A.

    2016-09-01

    This paper presents a self-consistent model for the evolution of gas produced in the debris disc of β Pictoris. Our model proposes that atomic carbon and oxygen are created from the photodissociation of CO, which is itself released from volatile-rich bodies in the debris disc due to grain-grain collisions or photodesorption. While the CO lasts less than one orbit, the atomic gas evolves by viscous spreading resulting in an accretion disc inside the parent belt and a decretion disc outside. The temperature, ionization fraction and population levels of carbon and oxygen are followed with the photodissociation region model CLOUDY, which is coupled to a dynamical viscous α model. We present new gas observations of β Pic, of C I observed with Atacama Pathfinder EXperiment and O I observed with Herschel, and show that these along with published C II and CO observations can all be explained with this new model. Our model requires a viscosity α > 0.1, similar to that found in sufficiently ionized discs of other astronomical objects; we propose that the magnetorotational instability is at play in this highly ionized and dilute medium. This new model can be tested from its predictions for high-resolution ALMA observations of C I. We also constrain the water content of the planetesimals in β Pic. The scenario proposed here might be at play in all debris discs and this model could be used more generally on all discs with C, O or CO detections.

  10. Relationship between disc injury and manual lifting: a poroelastic finite element model study.

    PubMed

    Natarajan, R N; Williams, J R; Lavender, S A; An, H S; Anderson, G B

    2008-02-01

    Understanding how failure originates in a lumbar motion segment subjected to loading conditions that are representative of manual lifting is important because it will pave the way for a better formulation of the exposure-injury relationship. The aim of the current investigation was to use a poroelastic finite element model of a human lumbar disc to determine its biomechanical characteristics under loading conditions that corresponded to three different, commonly occurring lifting activities and to identify the most hazardous type of loading with regard to damage to the disc. The current study showed that asymmetric lifting may increase the risk of back injury and pain. Lifting that involved lateral bending (asymmetric lifting) of the trunk was found to produce stresses at a localized area in the annulus, annuluar fibres, end plates, and facet joints that were higher than their respective tissue failure strength. Thus asymmetric lifting, if performed over a large number of cycles, might help to propagate this localized failure of the disc tissue to a larger area, owing to fatigue. The analyses also showed that largest fluid exchange between the nucleus and the end plates occurred during asymmetric lifting. If the fluid exchange is restricted owing to end plate calcification or sclerosis of the subchondral bone, high intradiscal pressure might develop, leading to higher disc bulge causing back pain.

  11. Signatures of massive collisions in debris discs. A self-consistent numerical model

    NASA Astrophysics Data System (ADS)

    Kral, Q.; Thébault, P.; Augereau, J.-C.; Boccaletti, A.; Charnoz, S.

    2015-01-01

    Context. Violent stochastic collisional events have been invoked as a possible explanation for some debris discs displaying pronounced azimuthal asymmetries or having a luminosity excess exceeding that expected for systems at collisional steady-state. So far, no thorough modelling of the consequences of such stochastic events has been carried out, mainly because of the extreme numerical challenge of coupling the dynamical and collisional evolution of the released dust. Aims: We perform the first fully self-consistent modelling of the aftermath of massive breakups in debris discs. We follow the collisional and dynamical evolution of dust released after the breakup of a Ceres-sized body at 6 AU from its central star. We investigate the duration, magnitude, and spatial structure of the signature left by such a violent event, as well as its observational detectability. Methods: We use the recently developed LIDT-DD code, which handles the coupled collisional and dynamical evolution of debris discs. The main focus is placed on the complex interplay between destructive collisions, Keplerian dynamics, and radiation pressure forces. We use the GRaTer package to estimate the system's luminosity at different wavelengths. Results: The breakup of a Ceres-sized body at 6 AU creates an asymmetric dust disc that is homogenized by the coupled action of collisions and dynamics on a timescale of a few 105 years. After a transient period where it is very steep, the particle size distribution in the system relaxes to a collisional steady-state law after ~104 years. The luminosity excess in the breakup's aftermath should be detectable by mid-IR photometry, from a 30 pc distance, over a period of ~106 years that exceeds the duration of the asymmetric phase of the disc (a few 105 years). As for the asymmetric structures, we derive synthetic images for the VLT/SPHERE and JWST/MIRI instruments, showing that they should be clearly visible and resolved from a 10 pc distance. Images at 1.6

  12. Longitudinal Changes in the Structure and Inflammatory Response of the Intervertebral Disc Due to Stab Injury in a Murine Organ Culture Model

    PubMed Central

    Abraham, Adam C.; Liu, Jennifer W.; Tang, Simon Y.

    2017-01-01

    Despite the significant public health impact of intervertebral disc (IVD) degeneration and low back pain, it remains challenging to investigate the multifactorial molecular mechanisms that drive the degenerative cascade. Organ culture model systems offer the advantage of allowing cells to live and interact with their native extracellular matrix, while simultaneously reducing the amount of biological variation and complexity present at the organismal level. Murine organ cultures in particular also allow the use of widely available genetically modified animals with molecular level reporters that would reveal insights on the degenerative cascade. Here, we utilize an organ culture system of murine lumbar functional spinal units where we are able to maintain the cellular, metabolic, and structural, and mechanical stability of the whole organ over a 21-day period. Furthermore, we describe a novel approach in organ culture by using tissues from animals with an NF-κB-luc reporter in combination with a mechanical injury model, and are able to show that proinflammatory factors and cytokines such as NF-κB and IL-6 produced by IVD cells can be monitored longitudinally during culture in a stab injury model. Taken together, we utilize a murine organ culture system that maintains the cellular and tissue level behavior of the intervertebral disc and apply it to transgenic animals that allow the monitoring of the inflammatory profile of IVDs. This approach could provide important insights on the molecular and metabolic mediators that regulate the homeostasis of the IVD. PMID:27273204

  13. Retinal degeneration in animal models with a defective visual cycle

    PubMed Central

    Maeda, Akiko; Palczewski, Krzysztof

    2014-01-01

    Continuous generation of visual chromophore through the visual (retinoid) cycle is essential to maintain eyesight and retinal heath. Impairments in this cycle and related pathways adversely affect vision. In this review, we summarize the chemical reactions of vitamin A metabolites involved in the retinoid cycle and describe animal models of associated human diseases. Development of potential therapies for retinal disorders in these animal models is also introduced. PMID:25210527

  14. The Besançon Galaxy model: comparisons to photometric surveys and modelling of the Galactic bulge and disc

    NASA Astrophysics Data System (ADS)

    Reylé, C.; Robin, A. C.; Schultheis, M.; Marshall, D. J.

    2010-12-01

    Exploring the in-plane region of our Galaxy is an interesting but challenging quest, because of the complex structure and the highly variable extinction. We here analyse photometric near-infrared data using the Besançon Galaxy Model in order to investigate the shape of the disc and bulge. We present new constraints on the stellar disc, which is shown to be asymmetric, and on the bulge, which is found to contain two populations. We present how the Galaxy model is used in the framework of the preparation of the Gaia mission.

  15. From the channel model of an InSb-based superresolution optical disc system to impulse response and resolution limits.

    PubMed

    Hepper, Dietmar

    2011-06-10

    The signal model of a superresolution optical channel can be an efficient tool for developing components of an associated high-density optical disc system. While the behavior of the laser diode, aperture, lens, and detector are properly described, a general mathematical model of the superresolution disc itself has not yet been available until recently. Different approaches have been made to describe the properties of a mask layer, mainly based on temperature- or power-dependent nonlinear effects. A complete signal-based or phenomenological optical channel model--from non-return-to-zero inverted input to disc readout signal--has recently been developed including the reflectivity of a superresolution disc with InSb used for the mask layer. In this contribution, the model is now extended and applied to a moving disc including a land-and-pit structure, and results are compared with data read from real superresolution discs. Both impulse response and resolution limits are derived and discussed. Thus the model provides a bridge from physical to readout signal properties, which count after all. The presented approach allows judging of the suitability of a mask layer material for storage density enhancement already based on static experiments, i.e., even before developing an associated disc drive.

  16. Yttrium oxide nanoparticles prevent photoreceptor death in a light-damage model of retinal degeneration.

    PubMed

    Mitra, Rajendra N; Merwin, Miles J; Han, Zongchao; Conley, Shannon M; Al-Ubaidi, Muayyad R; Naash, Muna I

    2014-10-01

    Photoreceptor (PR) cells are prone to accumulation of reactive oxygen species (ROS) and oxidative stress. An imbalance between the production of ROS and cellular antioxidant defenses contributes to PR degeneration and blindness in many different ocular disease states. Yttrium oxide (Y2O3) nanoparticles (NPs) are excellent free radical scavengers owing to their nonstoichiometric crystal defects. Here we utilize a murine light-stress model to test the efficacy of Y2O3 NPs (~10-14nm in diameter) in ameliorating retinal oxidative stress-associated degeneration. Our studies demonstrate that intravitreal injections of these NPs at doses ranging from 0.1 to 5.0µM 2 weeks before acute light stress protect PRs from degeneration. This protection is reflected both structurally (i.e., decreased light-associated thinning of the outer nuclear layer) and functionally (i.e., preservation of scotopic and photopic electroretinogram amplitudes). We also observe preservation of structure and function when NPs are delivered immediately after acute light stress, although the magnitude of the preservation is smaller, and only doses ranging from 1.0 to 5.0µM were effective. We show that the Y2O3 NPs are nontoxic and well tolerated after intravitreal delivery. Our results suggest that Y2O3 NPs have astonishing antioxidant benefits and, with further exploration, may be an excellent strategy for the treatment of oxidative stress associated with multiple forms of retinal degeneration.

  17. Loss of Ikbkap Causes Slow, Progressive Retinal Degeneration in a Mouse Model of Familial Dysautonomia

    PubMed Central

    Ramirez, Grisela

    2016-01-01

    Abstract Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy that is caused by a mutation in the gene for inhibitor of kappa B kinase complex-associated protein (IKBKAP). Although FD patients suffer from multiple neuropathies, a major debilitation that affects their quality of life is progressive blindness. To determine the requirement for Ikbkap in the developing and adult retina, we generated Ikbkap conditional knockout (CKO) mice using a TUBA1a promoter-Cre (Tα1-Cre). In the retina, Tα1-Cre expression is detected predominantly in retinal ganglion cells (RGCs). At 6 months, significant loss of RGCs had occurred in the CKO retinas, with the greatest loss in the temporal retina, which is the same spatial phenotype observed in FD, Leber hereditary optic neuropathy, and dominant optic atrophy. Interestingly, the melanopsin-positive RGCs were resistant to degeneration. By 9 months, signs of photoreceptor degeneration were observed, which later progressed to panretinal degeneration, including RGC and photoreceptor loss, optic nerve thinning, Müller glial activation, and disruption of layers. Taking these results together, we conclude that although Ikbkap is not required for normal development of RGCs, its loss causes a slow, progressive RGC degeneration most severely in the temporal retina, which is later followed by indirect photoreceptor loss and complete retinal disorganization. This mouse model of FD is not only useful for identifying the mechanisms mediating retinal degeneration, but also provides a model system in which to attempt to test therapeutics that may mitigate the loss of vision in FD patients. PMID:27699209

  18. Towards a fully consistent Milky Way disc model - I. The local model based on kinematic and photometric data

    NASA Astrophysics Data System (ADS)

    Just, A.; Jahreiß, H.

    2010-02-01

    We present a fully consistent evolutionary disc model of the solar cylinder. The model is based on a sequence of stellar subpopulations described by the star formation history (SFR) and the dynamical heating law [given by the age-velocity dispersion relation (AVR)]. The stellar subpopulations are in dynamical equilibrium and the gravitational potential is calculated self-consistently including the influence of the dark matter halo and the gas component. The combination of kinematic data from Hipparcos and the finite lifetimes of main-sequence (MS) stars enables us to determine the detailed vertical disc structure independent of individual stellar ages and only weakly dependent on the initial mass function (IMF). The disc parameters are determined by applying a sophisticated best-fitting algorithm to the MS star velocity distribution functions in magnitude bins. We find that the AVR is well constrained by the local kinematics, whereas for the SFR the allowed range is larger. The model is consistent with the local kinematics of MS stars and fulfils the known constraints on scaleheights, surface densities and mass ratios. A simple chemical enrichment model is included in order to fit the local metallicity distribution of G dwarfs. In our favoured Model A, the power-law index of the AVR is 0.375 with a minimum and maximum velocity dispersion of 5.1 and 25.0km s-1, respectively. The SFR shows a maximum 10 Gyr ago and declines by a factor of four to the present-day value of 1.5Msolarpc-2Gyr-1. A best fit of the IMF leads to power-law indices of -1.46 below and -4.16 above 1.72Msolar avoiding a kink at 1Msolar. An isothermal thick-disc component with local density of ~6 per cent of the stellar density is included. A thick disc containing more than 10 per cent of local stellar mass is inconsistent with the local kinematics of K and M dwarfs. Neglecting the thick-disc component results in slight variations of the thin-disc properties, but has a negligible influence on the

  19. Cervical Total Disc Arthroplasty

    PubMed Central

    Basho, Rahul; Hood, Kenneth A.

    2012-01-01

    Symptomatic adjacent segment degeneration of the cervical spine remains problematic for patients and surgeons alike. Despite advances in surgical techniques and instrumentation, the solution remains elusive. Spurred by the success of total joint arthroplasty in hips and knees, surgeons and industry have turned to motion preservation devices in the cervical spine. By preserving motion at the diseased level, the hope is that adjacent segment degeneration can be prevented. Multiple cervical disc arthroplasty devices have come onto the market and completed Food and Drug Administration Investigational Device Exemption trials. Though some of the early results demonstrate equivalency of arthroplasty to fusion, compelling evidence of benefits in terms of symptomatic adjacent segment degeneration are lacking. In addition, non-industry-sponsored studies indicate that these devices are equivalent to fusion in terms of adjacent segment degeneration. Longer-term studies will eventually provide the definitive answer. PMID:24353955

  20. Intervertebral disc response to cyclic loading--an animal model.

    PubMed

    Ekström, L; Kaigle, A; Hult, E; Holm, S; Rostedt, M; Hansson, T

    1996-01-01

    The viscoelastic response of a lumbar motion segment loaded in cyclic compression was studied in an in vivo porcine model (N = 7). Using surgical techniques, a miniaturized servohydraulic exciter was attached to the L2-L3 motion segment via pedicle fixation. A dynamic loading scheme was implemented, which consisted of one hour of sinusoidal vibration at 5 Hz, 50 N peak load, followed by one hour of restitution at zero load and one hour of sinusoidal vibration at 5 Hz, 100 N peak load. The force and displacement responses of the motion segment were sampled at 25 Hz. The experimental data were used for evaluating the parameters of two viscoelastic models: a standard linear solid model (three-parameter) and a linear Burger's fluid model (four-parameter). In this study, the creep behaviour under sinusoidal vibration at 5 Hz closely resembled the creep behaviour under static loading observed in previous studies. Expanding the three-parameter solid model into a four-parameter fluid model made it possible to separate out a progressive linear displacement term. This deformation was not fully recovered during restitution and is therefore an indication of a specific effect caused by the cyclic loading. High variability was observed in the parameters determined from the 50 N experimental data, particularly for the elastic modulus E1. However, at the 100 N load level, significant differences between the models were found. Both models accurately predicted the creep response under the first 800 s of 100 N loading, as displayed by mean absolute errors for the calculated deformation data from the experimental data of 1.26 and 0.97 percent for the solid and fluid models respectively. The linear Burger's fluid model, however, yielded superior predictions particularly for the initial elastic response.

  1. Imbalanced Protein Expression Patterns of Anabolic, Catabolic, Anti-Catabolic and Inflammatory Cytokines in Degenerative Cervical Disc Cells: New Indications for Gene Therapeutic Treatments of Cervical Disc Diseases

    PubMed Central

    Mern, Demissew S.; Beierfuß, Anja; Fontana, Johann; Thomé, Claudius; Hegewald, Aldemar A.

    2014-01-01

    Degenerative disc disease (DDD) of the cervical spine is common after middle age and can cause loss of disc height with painful nerve impingement, bone and joint inflammation. Despite the clinical importance of these problems, in current publications the pathology of cervical disc degeneration has been studied merely from a morphologic view point using magnetic resonance imaging (MRI), without addressing the issue of biological treatment approaches. So far a wide range of endogenously expressed bioactive factors in degenerative cervical disc cells has not yet been investigated, despite its importance for gene therapeutic approaches. Although degenerative lumbar disc cells have been targeted by different biological treatment approaches, the quantities of disc cells and the concentrations of gene therapeutic factors used in animal models differ extremely. These indicate lack of experimentally acquired data regarding disc cell proliferation and levels of target proteins. Therefore, we analysed proliferation and endogenous expression levels of anabolic, catabolic, ant-catabolic, inflammatory cytokines and matrix proteins of degenerative cervical disc cells in three-dimensional cultures. Preoperative MRI grading of cervical discs was used, then grade III and IV nucleus pulposus (NP) tissues were isolated from 15 patients, operated due to cervical disc herniation. NP cells were cultured for four weeks with low-glucose in collagen I scaffold. Their proliferation rates were analysed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide. Their protein expression levels of 28 therapeutic targets were analysed using enzyme-linked immunosorbent assay. During progressive grades of degeneration NP cell proliferation rates were similar. Significantly decreased aggrecan and collagen II expressions (P<0.0001) were accompanied by accumulations of selective catabolic and inflammatory cytokines (disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix

  2. Imbalanced protein expression patterns of anabolic, catabolic, anti-catabolic and inflammatory cytokines in degenerative cervical disc cells: new indications for gene therapeutic treatments of cervical disc diseases.

    PubMed

    Mern, Demissew S; Beierfuβ, Anja; Fontana, Johann; Thomé, Claudius; Hegewald, Aldemar A

    2014-01-01

    Degenerative disc disease (DDD) of the cervical spine is common after middle age and can cause loss of disc height with painful nerve impingement, bone and joint inflammation. Despite the clinical importance of these problems, in current publications the pathology of cervical disc degeneration has been studied merely from a morphologic view point using magnetic resonance imaging (MRI), without addressing the issue of biological treatment approaches. So far a wide range of endogenously expressed bioactive factors in degenerative cervical disc cells has not yet been investigated, despite its importance for gene therapeutic approaches. Although degenerative lumbar disc cells have been targeted by different biological treatment approaches, the quantities of disc cells and the concentrations of gene therapeutic factors used in animal models differ extremely. These indicate lack of experimentally acquired data regarding disc cell proliferation and levels of target proteins. Therefore, we analysed proliferation and endogenous expression levels of anabolic, catabolic, ant-catabolic, inflammatory cytokines and matrix proteins of degenerative cervical disc cells in three-dimensional cultures. Preoperative MRI grading of cervical discs was used, then grade III and IV nucleus pulposus (NP) tissues were isolated from 15 patients, operated due to cervical disc herniation. NP cells were cultured for four weeks with low-glucose in collagen I scaffold. Their proliferation rates were analysed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide. Their protein expression levels of 28 therapeutic targets were analysed using enzyme-linked immunosorbent assay. During progressive grades of degeneration NP cell proliferation rates were similar. Significantly decreased aggrecan and collagen II expressions (P<0.0001) were accompanied by accumulations of selective catabolic and inflammatory cytokines (disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix

  3. Degenerate Bogdanov-Takens bifurcations in a one-dimensional transport model of a fusion plasma

    NASA Astrophysics Data System (ADS)

    de Blank, H. J.; Kuznetsov, Yu. A.; Pekkér, M. J.; Veldman, D. W. M.

    2016-09-01

    Experiments in tokamaks (nuclear fusion reactors) have shown two modes of operation: L-mode and H-mode. Transitions between these two modes have been observed in three types: sharp, smooth and oscillatory. The same modes of operation and transitions between them have been observed in simplified transport models of the fusion plasma in one spatial dimension. We study the dynamics in such a one-dimensional transport model by numerical continuation techniques. To this end the MATLAB package CL_MATCONTL was extended with the continuation of (codimension-2) Bogdanov-Takens bifurcations in three parameters using subspace reduction techniques. During the continuation of (codimension-2) Bogdanov-Takens bifurcations in 3 parameters, generically degenerate Bogdanov-Takens bifurcations of codimension-3 are detected. However, when these techniques are applied to the transport model, we detect a degenerate Bogdanov-Takens bifurcation of codimension 4. The nearby 1- and 2-parameter slices are in agreement with the presence of this codimension-4 degenerate Bogdanov-Takens bifurcation, and all three types of L-H transitions can be recognized in these slices. The same codimension-4 situation is observed under variation of the additional parameters in the model, and under some modifications of the model.

  4. ELECTRON MICROSCOPIC AND HISTOCHEMICAL OBSERVATIONS OF MUSCLE DEGENERATION AFTER TOURNIQUET

    PubMed Central

    Moore, Dan H.; Ruska, Helmut; Copenhaver, Wilfred M.

    1956-01-01

    As an experimental model for the different forms of muscle degeneration, injury caused by 2 hours' ischemia has been studied from 20 minutes to 16 hours after release of the tourniquet. Discoid degeneration developed in stretched fibers by dissolution of the I bands (Z substances and actin). The discs represented the Q bands (A-H-A). In fibers which passively maintained contraction lengths during degeneration, the Z substances were dissolved, but the continuity of the fibrils was preserved, since the filaments are continuous over all sarcomeres under these conditions. Mitochondria and the tubules of the endoplasmic reticulum swelled, ruptured, and disintegrated. Granular degeneration developed in fibers where mitochondria were abundant. Unstretched degenerating fibers with few mitochondria gave a homogeneous or hyaline appearance. The different forms of degeneration therefore were dependent on the status of stretch and the fiber type. The extent of degeneration was not a function of time after ischemia, there being both nearly normal and severely damaged fibers at 20 minutes and 16 hours after the release of tourniquets. When degeneration occurred, however, the basic alterations were the same in all fibers; there was mitochondrial and reticular swelling, dissolution of the Z substances, and finally disintegration of the contractile material. Some damage developed in the sarcolemmas and capillaries. The mitochondrial disintegration was not linked with inactivation of the succinic dehydrogenase system. PMID:13398442

  5. Sensitivity of notochordal disc cells to mechanical loading: an experimental animal study.

    PubMed

    Guehring, Thorsten; Nerlich, Andreas; Kroeber, Markus; Richter, Wiltrud; Omlor, Georg W

    2010-01-01

    The immature disc nucleus pulposus (NP) consists of notochordal cells (NCs). With maturation NCs disappear in humans, to be replaced by chondrocyte-like mature NP cells (MNPCs); this change in cell phenotype coincidences with early signs of disc degeneration. The reasons for NC disappearance are important to understand disc degeneration, but remain unknown, yet. This study investigated, whether loading induced a change from a notochordal nucleus phenotype to a chondrocyte-like one. An in vivo disc compression model with fixateur externe was used in 36 mature rabbits. Discs were compressed for different time periods (1, 28, 56 days), and compared with uncompressed control discs (56 days without treatment), and discs with sham compression (28 days). Nucleus cell phenotype was determined by histology and immunohistochemistry. NCs, but not MNPCs highly expressed bone-morphogenetic-protein 2 and cytokeratin 8, thus NC and MNPC numbers could be determined. A histologic score was used to detect structural endplate changes after compression (28 days). Control and sham compressed discs contained around 70% NCs and 30% MNPCs, to be decreased to <10% NCs after 28-56 days of loading. NC density fell sharply by >50% after 28-56 days of compression (P < 0.05 vs. controls). Signs of decreased endplate cellularity and increased endplate sclerosis and fibrosis were found after loading. These experiments show that NCs were less resistant to mechanical stress than MNPCs suggesting that increased intradiscal pressures after loading, and limited nutrition through structurally altered endplates could instigate the disappearance of NCs.

  6. Development and Translation of a Tissue-Engineered Disc in a Preclinical Rodent Model

    DTIC Science & Technology

    2013-10-01

    in which all surgery and fixation conditions are the same, but without disc removal or DAPS placement. Given that Aims 2 and Aim 3 are both in...Implantation Model in the Rat Caudal Spine: Our first step in this work was pilot surgeries (with a few acellular DAPS) in Years 1 and 2 to establish...minimally invasive in order to prevent vascular damage and promote rapid healing. Three surgical groups were evaluated: sham, discectomy and implantation

  7. Melatonin delays photoreceptor degeneration in a mouse model of autosomal recessive retinitis pigmentosa.

    PubMed

    Xu, Xiao-Jian; Wang, Shu-Min; Jin, Ying; Hu, Yun-Tao; Feng, Kang; Ma, Zhi-Zhong

    2017-10-01

    Retinitis pigmentosa (RP) comprises a group of incurable inherited retinal degenerations. Targeting common processes, instead of mutation-specific treatment, has proven to be an innovative strategy to combat debilitating retinal degeneration. Growing evidence indicates that melatonin possesses a potent activity against neurodegenerative disorders by mitigating cell damage associated with apoptosis and inflammation. Given the pleiotropic role of melatonin in central nervous system, the aim of the present study was to investigate whether melatonin would afford protection against retinal degeneration in autosomal recessive RP (arRP). Rd10, a well-characterized murine model of human arRP, received daily intraperitoneal injection of melatonin (15 mg/kg) between postnatal day (P) 13 and P30. Retinas treated with melatonin or vehicle were harvested for analysis at P30 and P45, respectively. The findings showed that melatonin could dampen the photoreceptors death and delay consequent retinal degeneration. We also observed that melatonin weakened the expression of glial fibrillary acidic protein (GFAP) in Müller cells. Additionally, melatonin could alleviate retinal inflammatory response visualized by IBA1 staining, which was further corroborated by downregulation of inflammation-related genes, such as tumor necrosis factor alpha (Tnf-α), chemokine (C-C motif) ligand 2 (Ccl2), and chemokine (C-X-C motif) ligand 10 (Cxcl10). These data revealed that melatonin could ameliorate retinal degeneration through potentially attenuating apoptosis, reactive gliosis, and microglial activation in rd10 mice. Moreover, these results suggest melatonin as a promising agent improving photoreceptors survival in human RP. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Investigation of degenerate dual-pump phase sensitive amplifier using multi-wave model.

    PubMed

    Xie, Weilin; Fsaifes, Ihsan; Labidi, Tarek; Bretenaker, Fabien

    2015-12-14

    Operation of a degenerate dual-pump phase sensitive amplifier (PSA) is thoroughly numerically investigated using a multi-wave model, taking into account high-order waves associated with undesired four-wave mixing (FWM) processes. More accurate phase-sensitive signal gain characteristics are obtained compared to the conventional 3-wave model, leading to precise optimization of the pump configuration in a degenerate dual-pump PSA. The signal gain for different pump configurations, as well as the phase sensitivity, is obtained and interpreted by investigating the dominant FWM processes in terms of the corresponding phase matching. Moreover, the relation between dispersion slope and the width of the signal gain curve versus the pump-pump wavelength separation is revealed, permitting the application-oriented arbitrary tailoring of the signal gains by manipulating the dispersion profile and pump wavelength allocation.

  9. Investigating the Andromeda stream - I. Simple analytic bulge-disc-halo model for M31

    NASA Astrophysics Data System (ADS)

    Geehan, J. J.; Fardal, M. A.; Babul, A.; Guhathakurta, P.

    2006-03-01

    This paper is the first in a series which studies interactions between M31 and its satellites, including the origin of the giant southern stream. We construct accurate yet simple analytic models for the potential of the M31 galaxy to provide an easy basis for the calculation of orbits in M31's halo. We use a Navarro, Frenk and White (NFW) dark halo, an exponential disc, a Hernquist bulge, and a central black hole point mass to describe the galaxy potential. We constrain the parameters of these functions by comparing to existing surface-brightness, velocity-dispersion, and rotation-curve measurements of M31. Our description provides a good fit to the observations, and agrees well with more sophisticated modelling of M31. While in many respects the parameter set is well constrained, there is substantial uncertainty in the outer halo potential and a near-degeneracy between the disc and halo components, producing a large, nearly two-dimensional allowed region in parameter space. We limit the allowed region using theoretical expectations for the halo concentration, baryonic content, and stellar mass-to-light ratio (M/LR), finding a smaller region where the parameters are physically plausible. Our proposed mass model for M31 has Mbulge= 3.2 × 1010Msolar, Mdisc= 7.2 × 1010Msolar, and M200= 7.1 × 1011Msolar, with uncorrected (for internal and foreground extinction) mass-to-light ratios of M/LR= 3.9 and 3.3 for the bulge and disc, respectively. We present some illustrative test-particle orbits for the progenitor of the stellar stream in our galaxy potential, highlighting the effects of the remaining uncertainty in the disc and halo masses.

  10. Modelling accretion disc and stellar wind interactions: the case of Sgr A*

    NASA Astrophysics Data System (ADS)

    Christie, I. M.; Petropoulou, M.; Mimica, P.; Giannios, D.

    2016-07-01

    Sgr A* is an ideal target to study low-luminosity accreting systems. It has been recently proposed that properties of the accretion flow around Sgr A* can be probed through its interactions with the stellar wind of nearby massive stars belonging to the S-cluster. When a star intercepts the accretion disc, the ram and thermal pressures of the disc terminate the stellar wind leading to the formation of a bow shock structure. Here, a semi-analytical model is constructed which describes the geometry of the termination shock formed in the wind. With the employment of numerical hydrodynamic simulations, this model is both verified and extended to a region prone to Kelvin-Helmholtz instabilities. Because the characteristic wind and stellar velocities are in ˜108 cm s-1 range, the shocked wind may produce detectable X-rays via thermal bremsstrahlung emission. The application of this model to the pericentre passage of S2, the brightest member of the S-cluster, shows that the shocked wind produces roughly a month long X-ray flare with a peak luminosity of L ≈ 4 × 1033 erg s-1 for a stellar mass-loss rate, disc number density, and thermal pressure strength of dot{M}_w= 10^{-7} M_{⊙} yr^{-1}, nd = 105 cm-3, and α = 0.1, respectively. This peak luminosity is comparable to the quiescent X-ray emission detected from Sgr A* and is within the detection capabilities of current X-ray observatories. Its detection could constrain the density and thickness of the disc at a distance of ˜3000 gravitational radii from the supermassive black hole.

  11. Modelling accretion disc and stellar wind interactions: the case of Sgr A.

    PubMed

    Christie, I M; Petropoulou, M; Mimica, P; Giannios, D

    2016-07-01

    Sgr A* is an ideal target to study low-luminosity accreting systems. It has been recently proposed that properties of the accretion flow around Sgr A* can be probed through its interactions with the stellar wind of nearby massive stars belonging to the S-cluster. When a star intercepts the accretion disc, the ram and thermal pressures of the disc terminate the stellar wind leading to the formation of a bow shock structure. Here, a semi-analytical model is constructed which describes the geometry of the termination shock formed in the wind. With the employment of numerical hydrodynamic simulations, this model is both verified and extended to a region prone to Kelvin-Helmholtz instabilities. Because the characteristic wind and stellar velocities are in ∼10(8) cm s(-1) range, the shocked wind may produce detectable X-rays via thermal bremsstrahlung emission. The application of this model to the pericentre passage of S2, the brightest member of the S-cluster, shows that the shocked wind produces roughly a month long X-ray flare with a peak luminosity of L ≈ 4 × 10(33) erg s(-1) for a stellar mass-loss rate, disc number density, and thermal pressure strength of [Formula: see text], nd = 10(5) cm(-3), and α = 0.1, respectively. This peak luminosity is comparable to the quiescent X-ray emission detected from Sgr A* and is within the detection capabilities of current X-ray observatories. Its detection could constrain the density and thickness of the disc at a distance of ∼3000 gravitational radii from the supermassive black hole.

  12. The three-dimension model for the rock-breaking mechanism of disc cutter and analysis of rock-breaking forces

    NASA Astrophysics Data System (ADS)

    Zhang, Zhao-Huang; Sun, Fei

    2012-06-01

    To study the rock deformation with three-dimensional model under rolling forces of disc cutter, by carrying out the circular-grooving test with disc cutter rolling around on the rock, the rock mechanical behavior under rolling disc cutter is studied, the mechanical model of disc cutter rolling around the groove is established, and the theory of single-point and double-angle variables is proposed. Based on this theory, the physics equations and geometric equations of rock mechanical behavior under disc cutters of tunnel boring machine (TBM) are studied, and then the balance equations of interactive forces between disc cutter and rock are established. Accordingly, formulas about normal force, rolling force and side force of a disc cutter are derived, and their validity is studied by tests. Therefore, a new method and theory is proposed to study rock-breaking mechanism of disc cutters.

  13. Properties of Flicker ERGs in Rat Models with Retinal Degeneration

    PubMed Central

    An, Jing; Guo, Qun; Li, Li; Zhang, Zuoming

    2012-01-01

    Purpose. To describe the characteristics of rod and cone functions in rat models for congenital stationary night blindness (CSNB) and retinal cone dysfunction (RCD). Methods. Rod and cone function were isolated by recording the rod-/cone-driven flicker and blue light flicker electroretinograms (ERGs). Results. During dark adaptation, the amplitudes of flicker ERGs in CSNB rats were lower than those in control rats; the responses of RCD rats were similar to control rats. During light adaptation, the amplitudes of flicker ERGs in CSNB rats were reduced; whereas the responses of RCD rats were not detected. Blue flicker ERGs were not observed in CSNB rats at lower frequencies. The cone driven critical flicker frequencies (CFFs) in control rats were 62 Hz. The rod driven CFF of RCD rats was 20 Hz; whereas the rod-/cone-driven CFF of CSNB rats both were about 25 Hz. Conclusions. The function of the rod system was damaged completely, the cones were the source of vision in CSNB rats. Rod system function is excellent in RCD rat. The rods of albinism rats are sensitive to frequencies less than 20 Hz; whereas the cones are sensitive to frequencies up to 62 Hz. PMID:24555124

  14. AAV-mediated gene therapy in mouse models of recessive retinal degeneration

    PubMed Central

    Pang, Ji-jing; Lei, Lei; Dai, Xufeng; Shi, Wei; Liu, Xuan; Dinculescu, Astra; McDowell, J. Hugh

    2013-01-01

    In recent years, more and more mutant genes that cause retinal diseases have been detected. At the same time, many naturally occurring mouse models of retinal degeneration have also been found, which show similar changes to human retinal diseases. These, together with improved viral vector quality allow more and more traditionally incurable inherited retinal disorders to become potential candidates for gene therapy. Currently, the most common vehicle to deliver the therapeutic gene into target retinal cells is the adeno-associated viral vector (AAV). Following delivery to the immuno-priviledged subretinal space, AAV-vectors can efficiently target both retinal pigment epithelium and photoreceptor cells, the origin of most retinal degenerations. This review focuses on the AAV-based gene therapy in mouse models of recessive retinal degenerations, especially those in which delivery of the correct copy of the wild-type gene has led to significant beneficial effects on visual function, as determined by morphological, biochemical, electroretinographic and behavioral analysis. The past studies in animal models and ongoing successful LCA2 clinical trials, predict a bright future for AAV gene replacement treatment for inherited recessive retinal diseases. PMID:22300136

  15. EVALUATION OF A TELEMEDICINE MODEL TO FOLLOW UP PATIENTS WITH EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

    PubMed

    Andonegui, Jose; Aliseda, Daniel; Serrano, Luis; Eguzkiza, Aitor; Arruti, Natalia; Arias, Luis; Alcaine, Araceli

    2016-02-01

    To evaluate a telemedicine model to follow up patients with exudative age-related macular degeneration and compare the time spent using this model with the time spent conducting office examinations. Results of office and telemedicine evaluations were compared to determine whether patients with exudative age-related macular degeneration previously treated with intravitreal injections needed additional treatment. The office examinations included visual acuity measurement, fundus examination, and optical coherence tomography. The telemedicine evaluation included evaluation of retinography images, optical coherence tomography images, and visual acuity data obtained in the office. We also measured the time spent on telemedicine evaluations and compared it with the time spent on office examinations. Twenty-one patients were included. A comparison of office and remote diagnostic decisions showed the same results in 181 cases. Among the 20 remaining patients and considering office diagnostic decisions as the gold standard, 17 (8%) patients had false-positive diagnoses and 3 (1%) had false-negative diagnoses. The sensitivity and specificity of the telemedicine evaluations were 96% and 85%, respectively. The average time spent on remote evaluations was 1 minute 21 seconds compared with 10 minutes spent on office examination (P < 0.001). The telemedicine model can be a useful alternative for following up patients with age-related macular degeneration.

  16. From hidden symmetry to extra dimensions: A five-dimensional formulation of the degenerate BESS model

    NASA Astrophysics Data System (ADS)

    Coradeschi, Francesco; de Curtis, Stefania; Dominici, Daniele

    2010-07-01

    We consider the continuum limit of a moose model corresponding to a generalization to N sites of the degenerate BESS model. The five-dimensional formulation emerging in this limit is a realization of a RS1 type model with SU(2)L⊗SU(2)R in the bulk, broken by boundary conditions and a vacuum expectation value on the infrared brane. A low-energy effective Lagrangian is derived by means of the holographic technique and corresponding bounds on the model parameters are obtained.

  17. From hidden symmetry to extra dimensions: A five-dimensional formulation of the degenerate BESS model

    SciTech Connect

    Coradeschi, Francesco; De Curtis, Stefania; Dominici, Daniele

    2010-07-01

    We consider the continuum limit of a moose model corresponding to a generalization to N sites of the degenerate BESS model. The five-dimensional formulation emerging in this limit is a realization of a RS1 type model with SU(2){sub L} x SU(2){sub R} in the bulk, broken by boundary conditions and a vacuum expectation value on the infrared brane. A low-energy effective Lagrangian is derived by means of the holographic technique and corresponding bounds on the model parameters are obtained.

  18. First results from the use of the relativistic and slim disc model SLIMULX in XSPEC

    NASA Astrophysics Data System (ADS)

    Caballero-Garcia, M. D.; Bursa, M.; Dovčiak, M.; Fabrika, S.; Castro-Tirado, A. J.; Karas, V.

    2017-07-01

    Ultra-Luminous X-ray sources (ULXs) are accreting black holes for which their X-ray properties have been seen to be different to the case of stellar-mass black hole binaries. For most of the cases their intrinsic energy spectra are well described by a cold accretion disc (thermal) plus a curved high-energy emission components. The mass of the black hole (BH) derived from the thermal disc component is usually in the range of 100-1000 solar masses, which have led to the idea that this might represent strong evidence of the Intermediate Mass Black Holes (IMBH), proposed to exist by theoretical studies but with no firm detection (as a class) so far. Recent theoretical and observational developments are leading towards the idea that these sources are instead stellar-mass BHs accreting at an unusual super-Eddington regime. In this paper we briefly describe the model SLIMULX that can be used in XSPEC for the fit of thermal spectra of slim discs around stellar mass BHs in the super-Eddington regime. This model consistently takes all relativistic effects into account. We present the obtained results from the fit of