bluuebunny/crossref_metadata_2025 huggingface dataset:
MMP 7, CALM 1, and Cox 2 Genes Influence Genetic Susceptibility of Lumbar Degenerative Disc Disease in Young Adults—Analysis of 58 Single Nucleotide Polymorphisms in 580 Individuals Based on Total Degenerative Disc Score
Authors: Rajasekaran S. , Kanna R. M. , Natesan S. , Muthurajan R. , Shetty A. P.
Published: May 2014

Introduction

Although the exact mechanisms that lead to degenerative disc disease (DDD) are not well understood, a significant genetic influence has been found. Focusing on DDD that occurs in young adults can be valuable in determining the exact role of genetic predisposition to DD. The present study was undertaken to assess the association between single nucleotide polymorphisms (SNPs) of candidate genes in a cohort of young Indian adults.

Materials and Methods

We selected young patients (age < 40 years) with lumbar disc degeneration and evaluated them with MRI and genetic association studies for 58 SNPs of 35 candidate genes. Disc degeneration of individual discs of lumbar spine from L1 to S1 was quantified by Pfirrmann grading in MRI images (1.5 T). The subjects were stratified into three groups based on a total degenerative disc score (TDDS). TDDS was developed by adding the individual scores of Pfirrmann grading of all the five lumbar discs. Based on the TDDS, the severity of DDD among the subjects was classified as mild (TDDS < 10), moderate (TDDS of 10-15), and severe (TDDS > 15). The patients were classified into three groups so that the extreme confounding patients in the mild and severe TDDS groups will automatically fall into the moderate TDDS group. For the final association analysis, only the results of mild (the unaffected, control group) and severe TDDS groups (affected, case group) were compared and analyzed.

Results

The study population comprised 580 subjects including 308 patients with mild TDDS, 211 patients with moderate TDDS, and 61 patients with severe TDDS. There was no significant difference in the gender difference and the mean age of the both groups. Three of the 35 candidate genes showed significant association with severe TDDS. SNPs, viz., rs1940044 of MMP (matrix metalloproteinase 7), rs2300496 SNP and rs3213718 SNPs of CALM1 (calmodulin), and rs5277 of COX 2 (cyclooxygenase) were found to be significantly associated with severe TDDS. Among the previously reported candidate genes, our analysis in the young Indian population had revealed that SNPs of COL 9, SKT, CHST 3, CILP, IGFR, SOXp, BMP, MMP 2-12, ADH2, IL1RN, AGC 1, ADAMTS5, NGFB, GLI, HHIP, TAC1, and IL1B were not significantly associated with severe TDDS. [Table: see text]

Conclusion

This is the first of its kind in studying the genetic aspects of disc degeneration in the young adults. The study identifies specific SNP associations of three genes (MMP 7, CALM 1, and COX2) in young adults with severe lumbar disc degeneration. Genes involved in matrix degradation (MMP), intracellular signaling (CALM), and inflammation (COX 2) were associated with early disc degeneration indicating that DDD is a complex disease with an intricate interplay of multiple genetic polymorphisms. Disclosure of Interest None declared
Associated Factors of Intervertebral Disc Degeneration—Current Results from a Population-Based Cohort: The Wakayama Spine Study
Authors: Hashizume H. , Teraguchi M. , Yoshimura N. , Yamada H. , Akune T. , Yoshida M.
Published: May 2014

Introduction

Intervertebral disc degeneration (DD) is thought to be the first step of degenerative spinal changes. Furthermore, DD is considered to be one of the causes of several symptoms including low back pain (LBP). Although previous studies have investigated the association between DD and LBP as well as risk factors of DD, many of them are still controversial mainly because of the selection bias for the cohort. The purposes of this study were (1) to examine the association between the presence of DD and low back pain, and (2) to examine the risk factors related to DD (age, gender, body mass index [BMI], hyperlipidemia, diabetes mellitus [DM], peripheral artery disease [PAD], and smoking) using a large scale population-based cohort.

Materials and Methods

This was a cross-sectional study of the base-line data from the population-based cohort of Wakayama, western part of Japan, comprising 975 (men, 324; women, 651; mean age 66.4 years) of 1,011 participants (age, 21-97 years). The participants were subjected to the entire spine MRI and the lumbar intervertebral disc was evaluated according to the Pfirrmann classification system (1-3 = nondegeneration; 4, 5 = degeneration). Multiple logistic regression analysis was used to estimate the association between DD and low back pain after adjustment for age, gender, and BMI. Besides this, we analyzed the association between the presence of DD and the potential risk factors: age, gender, BMI, hyperlipidemia, diabetes mellitus (DM), peripheral artery disease (PAD), and smoking.

Results

The presence of DD was significantly associated with low back pain. The multiple logistic regression analysis indicated that older age, obesity, and hyperlipidemia were significant related factors of DD. Gender, DM, PAD, and smoking were not significantly related with DD in our cohort.

Conclusion

The current data provide the foundation for elucidating the causes and mechanisms of DD. However, there is a limitation concerning a temporal relationship between exposure and outcome due to the nature of cross-sectional study design. The second survey of the cohort, which is now ongoing, will provide important information in the near future. Disclosure of Interest None declared Reference Teraguchi M, Yoshimura N, Hashizume H, et al. Prevalence and distribution of intervertebral disc degeneration over the entire spine in a population-based cohort: the Wakayama Spine Study. Osteoarthritis Cartilage 2014;22(1):104–110
Comprehensive Analysis of MRI-Phenotypes Provides New Insights into Lumbar Disc Degeneration for Genetic Studies
Authors: Li Y. , Samartzis D. , Campbell D. , Cheung K. , Luk K. , Karppinen J. , Cheah K. , Chan D. , Sham P.
Published: May 2014

Introduction

For the past two decades, numerous genetic association studies addressing lumbar disc degeneration (LDD) have been performed, but few of them can be replicated. The possible reasons could be the phenotype definition of LDD was highly variable between studies and level-specific variations were not addressed. As such, this study addressed the relationship between MRI features of the discs at different lumbar levels to explore the etiology of LDD; thereby, providing new insights and measurements for genetic studies.

Materials and Methods

Sagittal T2-weighted MRI of the lumbar spine was assessed in a population sample of 2,952 Southern Chinese (mean age, 41.1 years; range, 15.0-65.4 years; 40.7% males; 59.3% females). Loss of disc signal intensity, disc bulges/extrusions, Schmorl nodes, high-intensity zones, and bone marrow changes were assessed on imaging. Subject demographics, environmental, and lifestyle factors were also evaluated. Pair-wised polychoric correlations between phenotypes in all five lumbar discs were performed using R v3.01 Heritability was estimated by Genome-wide Complex Trait Analysis (GCTA) using genotype data to identify phenotypes shared common genetic factors. Local regressions were performed between conditions and risk factors, such as age and body mass index, to distinguish the relationship between phenotypes and environmental factors. Phenotypes which were highly correlated and shared common genetic factors were grouped to form a new measurement.

Results

Analyses suggested distinct genetic etiologies for the upper (L1-L2) versus lower regions (L3-S1). Estimation of heritability showed the upper (L1-L2) and lower regions (L3-S1) of the lumbar spine shared common genetics factors, respectively; but upper and lower regions could present independent genetic features. Regression between phenotype and age denoted that age-related condition was restricted to lower regions while the upper region suggests developmental characters. By combining highly correlated MRI phenotypes in the upper and lower regions separately, two composite scores were generated: a degenerative score (DgS) (represents age-related disc changes) and a developmental score (DvS) (represents congenital variations).

Conclusion

Based on one of the largest population-based MRI studies of LDD, comprehensive analyses of MRI phenotypes provided new insights into its etiology. Our study proposes a novel phenotype scoring system to assess disc changes on MRI. This scoring system can be used as the basis to promote a standardization of phenotype delineation, maximizing the potential of replication and meta-analysis studies of genetic risk factors for LDD. Disclosure of Interest None declared
Facet Joint Orientation and Tropism in Lumbar Degenerative Disc Disease and Spondylolisthesis
Authors: Chotiyarnwong P. , Pichaisak W.
Published: May 2014

Introduction

Back pain is one of the most common reported health problems in elderly. Two common causes of back pain were included in this study, degenerative disc disease (DDD) and spondylolisthesis (DS). Since facet joint is one of many structures that provide stability for spine, so this study will focus on the facet joint angle of patient. The association between lumbar facet joint angle and tropism in DDD and DS remain unclear.

Materials and Methods

The angle and tropism of lumbar facet joint were retrospectively studied with magnetic resonance imaging (MRI) in 180 subjects to determine whether there is a difference between degenerative diseases. MRI of patients with DDD, DS, and control group at facet joint between L3-4, L4-5, and L5-S1 levels were measured in axial view that can clearly see facet joint (60 subjects in each group).

Results

There is no different in facet joint angle in DDD (44.1 ± 11.9) and control (45.6 ± 8.9) but different in DS (40.1 ± 10.7) and control group ( p = 0.010) at L4-5 level. Facet tropism shows different between degenerative and control groups (mean different = 2.9 degrees, p = 0.007 in DDD and mean different = 2.2 degrees, p = 0.046 in DS) at L4-5 level.

Conclusion

This study confirms a significant different between facet joints angle at L4-L5 in DS and normal population. Facet tropism in DDD and DS were shown significantly different to normal population. Additional, longitudinal studies are needed to understand the clinical significant in relationship between facet joint angle and tropism in spinal degenerative diseases. Disclosure of Interest None declared References Boden SD, Riew KD, Yamaguchi K, Branch TP, Schellinger D, Wiesel SW. Orientation of the lumbar facet joints: association with degenerative disc disease. J Bone Joint Surg Am 1996;78(3):403–411 Kalichman L, Suri P, Guermazi A, Li L, Hunter DJ. Facet orientation and tropism: associations with facet joint osteoarthritis and degeneratives. Spine 2009;34(16):E579-E585 Don AS, Robertson PA. Facet joint orientation in spondylolysis and isthmic spondylolisthesis. J Spinal Disord Tech 2008;21(2):112–115
DNA Demethylation Regulates Anabolic and Catabolic Gene Expression in Intervertebral Disc Cells
Authors: Chutkan N. , Sangani R. , Zhou H. , Fulzele S.
Published: May 2014

Introduction

The intervertebral disc (IVD) cell distribution depends on the developmental stage of the human disc. DNA methylation has been shown to be essential to mammalian development, and aberrant methylation patterns are a common feature of many kinds of age-related diseases. We hypothesize that the methylation status of the promoter region of the genomic DNA regulates gene expression of IVD cells.

Materials and Methods

IVD tissues were obtained from donors undergoing anterior lumbar discectomy procedures with Institutional Review Board approval. The tissues were transported to the laboratory, minced, and immediately underwent cell isolation by sequential enzyme digestion. The digested cells were centrifuged and seeded in culture dishes, supplemented with complete medium (DMEM/F12) containing 10% fetal bovine serum (FBS), 1% L-glutamine, and 1% antibiotic. The demethylation agent 5-azacytidine (5-aza-C) was used to inhibit DNA methylation in IVD cells. The cells were then plated and treated with 5-aza-C followed by RNA isolation and real time PCR for gene analysis.

Results

We investigated important cytokines (IL-1b, IL-6), anabolic genes (Aggrecan, Collagen type II), apoptotic (Bax), and cell cycle (p16, cyclin D2) genes following 5-aza-C. In the presence of 5-azaC treatment, IL-1b, IL-6, Bax, p16, and cyclin D2 expression were upregulated approximately twofold or more. The anabolic gene aggrecan was downregulated whereas no effect on collagen type II expression.

Conclusion

The experimentally induced loss of DNA methylation results in the increase expression of apoptotic, catabolic, and inflammatory genes. Furthermore, anabolic genes aggrecan significantly downregulated in 5-azacytidine treated samples, thus confirming a cause-and-effect relationship between DNA demethylation and transcription of these genes in IVD cells. DNA demethylation has been previously shown to inhibit cell proliferation and induce apoptotic cell death in different cell types. Our results suggest that demethylation of IVD cells may be one of the influential causes for IVD degeneration. Further studies are required to confirm our findings. Disclosure of Interest None declared
CK8 Phosphorylation Induced by Compressive Loads Underlies the Downregulation of CK8 in Human Disc Degeneration by Activating Protein Kinase C
Authors: Sun Z. , Luo Z.
Published: May 2014

Introduction

Cytokeratin 8 (CK8) is a member of the cytokeratins family with multiple functions on the basis of its unique structural hallmark. The aberrant expression of CK8 and its phosphorylation are pertinent with various diseases. We have previously shown that CK8 exists in normal human nucleus pulposus (NP) cells and decreases as the intervertebral disc degenerates. However, the underlying molecular regulatory machinery of CK8 in intervertebral disc degeneration (IDD) has not been clarified.

Materials and Methods

NP samples were collected from patients with idiopathic scoliosis as control and IDD as degenerate groups. Phosphorylation of CK8 was detected. Moreover, NP cells were cultured under different compressive load schemes for diverse time duration.

Results

We found that CK8 expression decreased in IDD with an increased phosphorylation in degenerate NP cells. Moreover, compressive loads resulted in phosphorylation and disassembly of CK8 in a time-dependent and degree-dependent manner in vitro. The activation of protein kinase C (PKC) was a significant molecular factor contributing to this phenomenon.

Conclusion

This study is the first addressing the molecular mechanisms of CK8 downregulation in NP cells. Importantly, our findings provide clues regarding a molecular link between compressive loads and CK8 alterations, which shed a novel light on the etiology of IDD. Disclosure of Interest None declared
Immortalization of Human Cartilage Endplate Stem Cell from Degenerated Human Intervertebral Disc
Authors: Liu M. , Huang B. , Zhou Y.
Published: May 2014

Introduction

Low back pain is one of the most common reasons for seeking medical advice and is a major cause of work-related disabilities. Recently, cell-based therapies for regenerating or repairing the degenerated disc have become treatment options. Our group previously demonstrated that stem cells exit in human degenerated CEP and that cartilage endplate-derived stem cells (CESCs) are superior to BM-MSCs in terms of osteogenesis and chondrogenesis. CESCs may represent one of the most promising stem cells for several degenerative conditions due to their multipotency, immunoprivileged properties, and easy expansion in vitro. However, the limited life span of primary CESCs during in vitro expansion greatly hampers their use in basic research and clinical applications. Immortalization of CESCs will overcome this problem and may provide a very useful tool with which to study CESCs biology.

Materials and Methods

Cells isolated from CEP were cultured in a three-dimensional agarose suspension to acquire proliferative cell clusters. As previous method, we acquire primary CESCs. Then with these cells we showed that silencing p53 expression with lentivirus-mediated small interfering RNA and overexpressing human telomerase reverse transcriptase (hTERT).

Results

The effects of p53 knockdown and hTERT overexpression on CESCs, including proliferation, colony formation, and differentiation, were determined. The resultant immortal CESCs displayed similar surface antigen profile to primary CESCs and retained CESCs differentiation potential. Gene expression profile showed high similarity between immortalized CESCs and primary CESCs. In addition, immortalization-associated genes were also identified.

Conclusion

This study provides a new stem cell resources for basic studies of characteristics of CESCs and understanding the mechanism of disc degeneration. Disclosure of Interest None declared
MRI-Based Classification of the Morphology and Pathology of the Annulus Fibrosus of the Intervertebral Disc
Authors: Benneker L. , Bonel H. , Weisstanner C. , Aghayev E. , Hoppe S.
Published: May 2014

Introduction

The high rate of recurrent disc herniation after discectomy is a prevalent problem. An effective biological annular repair could improve the surgical outcome in patients with contained disc herniation but otherwise minor degenerative changes. To estimate the integrity of the annulus fibrosus (AF) and judge different repair options a better understanding of disc morphology and pathology is crucial.1 Axial- and sagittal T2*-mapping are effective to detect early stages of degenerative disc disease and are especially suited to evaluate the interface between the proton-rich nucleus pulposus and the fibers of the annulus fibrosus.2,3 So far there is no classification of AF morphology or pathology as current classifications only describe localization and extend of the hernia itself.

Materials and Methods

Prospective consecutive case study of 100 patients requiring MRI diagnostic for suspected lumbar disc herniation. Beside the clinical standard MRI protocol with sagittal T1- and T2-weighted images, axial and sagittal T2*-mapping sequences of the affected and adjacent discs were performed using 3T MRI. Three observers used established classification schemes to assess the grade of degeneration (Pfirrmann, Benneker, Watanabe) and herniation (Carragee, Rajaserakan) and also developed a new classification protocol specific for the annulus fibrosus.

Results

In the preliminary data four types of annulus morphology/pathology could be found: type 1: healthy, uniform thickness of AF, clear demarcation between nucleus pulposus (NP) and AF. Type 2: concentric thinning with bulge, concentric tears, demarcation between NP and AF unclear. Type 3: nonconcentric thinning, ±radial fissures, ±protrusion, and type 4: herniations with further subgroups.

Conclusion

Based on preliminary axial and sagittal T2* images a new classification system for AF morphology and pathology could be established. Inter- and intraobserver liability is high. Disclosure of Interest None declared References Guterl CC, See EY, Blanquer SB, et al. Challenges and strategies in the repair of ruptured annulus fibrosus. Eur Cell Mater 2013;25:1–21 Stelzeneder D, Welsch GH, Kovács BK, et al. Quantitative T2 evaluation at 3.0T compared to morphological grading of the lumbar intervertebral disc: a standardized evaluation approach in patients with low back pain. Eur J Radiol 2012;81(2):324–330 Hoppe S, Quirbach S, Mamisch TC, Krause FG, Werlen S, Benneker LM. Axial T2 mapping in intervertebral discs: a new technique for assessment of intervertebral disc degeneration. Eur Radiol 2012;22(9):2013–2019
Study to Determine the Presence of Progenitor Cells in the Degenerated Human Cartilage Endplates
Authors: Huang B. , Liu L. , Li C. , Zhuang Y. , Luo G. , Hu H. , Zhou Y.
Published: May 2014

Introduction

Cartilage endplate (CEP) degeneration is usually accompanied by loss of cellularity, and this loss may be a crucial key factor in initiation and development of degenerative disc disease. The study of cell types in degenerated CEP could help in understanding CEP etiopathogenesis, and may help in devising new treatments, especially if the presence of progenitor cells could be demonstrated. The aim of this study, was to determine if progenitor cells existed in degenerated human CEP.

Materials and Methods

Cells isolated from CEP were cultured in a three-dimensional agarose suspension to screen for proliferative cell clusters. Cell clusters were then expanded in vitro and the populations were analyzed for colony forming unit (CFU), immunophenotype, multilineage induction, and expression of stem cell-related genes.

Results

The presence of progenitor cells in degenerated human CEP is indicated by the results of CFU, immunophenotype, multilineage induction, and expression of stem cell-related genes.

Conclusion

We believe that this is the first study, which has conclusively shown the presence of progenitor cells in degenerated CEP. The finding of this study may influence the clinical management of degenerative disc disorder. Disclosure of Interest None declared
Human Degenerate Discs Show Increased Activation of Intracellular Signalling Pathways of IL-1
Authors: Daniels J. , Binch A. LA. , Dunn S. , Phillips K. L. , Chiverton N. , Cole A. , Michael A. R. , Breakwell L. , Le Maitre C. L.
Published: May 2014

Introduction

Intervertebral disc degeneration is implicated in 40% of low back pain cases. Interleukin 1 (IL-1) is known to be important in the pathogenesis of intervertebral disc (IVD) degeneration, here we investigated the intracellular signaling pathways activated by IL-1 and determined the activation status of these pathways in native IVD tissues highlighting potential pathways for new therapies.

Materials and Methods

Human nucleus pulposus cells (NP) removed during discetomy for nerve root pain were stimulated with IL-1 for 30 minutes. The activation of ERK1/2, p38, c-jun, and IκB were determined using cell-based enzyme-linked immunosorbent assays, in addition pNFκB localisation in stimulated cells was determined using immunohistochemistry. Localisation of phosphorylated c-jun, p38, ERK1/2, and NFκB together with IL-1 was investigated within paraffin embedded sections of human IVD to investigate the presence of active pathways in vivo . Pretreatment with inhibitors of p38, c-jun, and NFκB for 30 minutes before stimulation with IL-1 (10 ng/mL) for 48 hours was investigated to determine the ability of individual signaling inhibitors to block the catabolic responses induced by IL-1.

Results

IL-1-induced activation of p38, MAPK, ERK ½, JNK/c-jun, and NFκB signaling pathways in human NP cells. IVD tissue samples displayed immunopositive staining for phosphorylated c-jun, ERK1/2, NFκB, and p38, immunopositivity was significantly increased within degenerate discs, particularly in those discs which also expressed high levels of IL-1. Inhibition of individual signaling pathways demonstrated differential regulation of the pleathora of IL-1-induced catabolic events, with different signaling molecules shown to regulate matrix metalloproteases, cytokines, and factors involved in innervation and angiogenesis of the disc.

Conclusion

Here, we have shown that the signaling pathways activated by IL-1 in vitro display increased activation in vivo during disc degeneration. Inhibitors of these pathways demonstrated multiple signaling pathways were involved in the pleathora of IL-1 actions. Thus, inhibition of signaling pathways could be a novel mechanism to inhibit catabolic processes which could hold promise to inhibit degeneration at early stages of disease but also create the correct tissue niche to promote regeneration of the disc. Disclosure of Interest None declared
A New Experimental Animal Model of Chronic Cervical Compressive Myelopathy
Authors: Zihe L. , Zhongjun L. , Gengding D. , Feng W.
Published: May 2014

Introduction

Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction among adults over the age of 55?In China the morbidity of CSM is 10%. However, the pathobiology of CSM is still unclear which limits therapeutic advances for this common cause of neurological dysfunction. The clinical course of the disease remains unpredictable. The lack of reliable animal models of CSM has been a restriction to advancing the field. Up to now, various animal model of CSM have been made. Although some of these studies have impressive progress, they also have significant defects. Many of these models fail to model the chronic and progressive nature of the disease since they do not accurately reproduce the main human neuropathological and clinical features of CSM, In this study we report a new model of CSM in sheep. It is more accurate and stable than previous models. Moreover, the entire course of compression is digitized.

Materials and Methods

A Silicone sealed compression device is assembled with a stepping motor, gear reducer and a push rod. The compression device is connected to a circuit board which contains a bluetooth module and a control chip. Power supply is a lithium battery. Circuit board is also well sealed with silicone. It is controlled via an Android cellphone in vitro. Six male small tailed han sheep were divided into two groups randomly, four in experimental group and two in control group. The compression device was implanted into intervertebral space of C4/C5 and fixed. Circuit board was implanted subcutaneously. The control group ran no compression after surgery. Animals of each group were carried on a routine CT inspection right after the surgery. The front end of the push rod was adjusted to the posterior edge of the cervical vertebral. The experimental group pushed 0.4 mm each week while awake. Tarlov scores were assessed in each group before and after push.

Results

In the course of the experiment, one sheep of the experimental group appeared malfunction of the circuit board subskin. The dysfunctional board was replaced during an extra operation. The Tarlov sores of the experimental group didn't change before and after each time of push. No behavioral changes were noted in control group. While sheep in the experimental group showed gradually changes of gait. The final Tarlov score was four in three sheep and three in one sheep of the experimental group and the final radiological findings showed that the average spinal canal encroachment rate was 60.6% in the experimental group after 18 weeks’ observation.

Conclusion

This animal model can be used to generate controllable compression to spine operated by a digitized system. No invasive procedures were applied during the experiment. In next stage of experiment we could get specimens and run pathological tests. Disclosure of Interest None declared
Intervertebral Disc Degenerative Changes after Intradiscal Injection of TNFα in a Porcine Model
Authors: Kang R. , Li H. , Ringgaard S. , Rickers K. , Xie L. , Bünger C.
Published: May 2014

Introduction

Tumor necrosis factor (TNF) has higher expression in degenerated disc tissues, thus be proposed as one of the initiators of causing disc degeneration. However, whether direct induction by TNFα leads to disc degeneration in vivo that has not been studied yet.

Materials and Methods

Two lumbar intervertebral discs in seven pigs were injected by 50 or 100 ng TNFα predisc, and with a third disc remaining intact as a normal control. Magnetic resonance imaging (MRI) including T1-, T2-weighted, T2-weighted 3D, sagittal-T2 mapping, was performed pre- and 3 months postintervention. Serial postcontrast T1-weighted MRI and histology study also performed at the end.

Results

After 3 months, these TNFα injected discs showed degenerative changes, with the percentage of disc height index, nucleus pulposus (NP) area, and NP T2 value lower than the normal controls. Serial postcontrast T1-weighted MRI showed increase diffusion in annulus and nucleus in TNFα injected discs compared with the normal controls. Histology confirmed these intervertebral disc degeneration changes, and found capillaries formation in annulus of TNFα injected discs. No significent difference was found between discs with different dose of TNF.

Conclusion

Intradiscal injection of TNFα lead to disc degeneration, and induce capillary ingrowth to disc in a pocine model. Disclosure of Interest None declared
Surgery in Pott Disease—Experience of 115 Cases
Authors: Alam M. Shah
Published: May 2014

Introduction

Tuberculosis (TB) of the spine is the most common and dangerous form of TB infection accounting 50 to 60% of osseous TB. Although, uncommon spinal TB still occurs even in both developed and developing countries. The diagnosis of spinal TB is difficult and it commonly presents at an advanced stage. Delay in establishing diagnosis and management cause spinal cord compression and spinal deformity.

Materials and Methods

A total of 30 patients who had TB of the thoracic and lumbar spine with moderate to severe cord compression was studied. Variable degrees of neurological deficit with deformity were treated at NITOR and PGHL, DHAKA during the period from 2008 to 2010. Anterolateral decompression and autogenous strut bone grafting with simultaneous fixation by screws and rod were done. Posterior decompression, posterior interbody, and posterolateral fusion by bone graft with stabilization by transpediculer screws and rods. Appropriate antituberculous drugs was given to all patients for 18 to 24 months. The postoperative follow-up period was 12 months (range 3-21 months).

Results

Ovearll 20 cases with neurological deficits recovered totally or partially. No neurological improvement had occurred in five cases with paraplegia. Five cases were lost from follow-up. X-ray shows bony fusion was achieved in all cases for mean of 6 months(range 4-8 months). There were no recurrences. Two cases had bed sores postoperatively and there was no neurological improvement.

Conclusion

For patients with thoracolumbar spinal TB anterior debridement, auto graft bone fusion, anterior or posterior fixation appears to be effective in arresting disease, correcting kyphotic deformity and maintaining correction until solid spinal fusion. Disclosure of Interest None declared
Characteristics of Spinopelvic Sagittal Alignment in Patients with Lumbar Disc Degenerative Diseases
Authors: Yang X. , Kong Q.
Published: May 2014

Introduction

A comparative study of the spinopelvic sagittal alignment in patients with lumbar disc degeneration or herniation (LDD/LDH) with normal population was designed to analyze roles of sagittal anatomical parameter (pelvic incidence, PI) and positional parameters in the pathogenesis and development of LDD/LDH. Several comparative studies of these patients with asymptomatic controls have been done. However, in previous studies without lumbar MRI, a certain number of asymptomatic LDD patients should have been included in the control group and then impacted on the results.

Materials and Methods

Total 60 LDD or LDH patients and 110 asymptomatic volunteers were included. Based on MRI, the normal group (NG) and degeneration group (DG) were divided. In DG, the symptomatic (SDG) and asymptomatic (ADG) subgroups were divided according to patients’ symptoms. Standing full-spine radiographs were used to measure sagittal parameters, including PI, sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), thoracic kyphosis (TK), sagittal vertical axis (SVA), and sacrum-bicoxofemoral distance (SFD).

Results

PI, SS, and LL in DG were significantly lower than NG while the SVA and SFD were significantly greater ( p < 0.05). PI correlated well with the SS and LL in all subjects; however the trend lines of SS or LL over PI were down-shifted in DG. Comparing SDG to ADG, PI was similar ( p = 0.716) but SS and LL were significantly lower and SVA was significantly greater ( p < 0.05).

Conclusion

PI may play a predisposing role in the pathogenesis of lumbar disc degenerative diseases. Moreover, the secondary structural and compensatory factors would lead to a straighter spine after disc degenerative change. Disclosure of Interest None declared References Barrey C, Jund J, Noseda O, Roussouly P. Sagittal balance of the pelvis-spine complex and lumbar degenerative diseases. A comparative study about 85 cases. Eur Spine J 2007;16(9):1459–1467 Rajnics P, Templier A, Skalli W, Lavaste F, Illes T. The importance of spinopelvic parameters in patients with lumbar disc lesions. Int Orthop 2002;26(2):104–108 Endo K, Suzuki H, Tanaka H, Kang Y, Yamamoto K. Sagittal spinal alignment in patients with lumbar disc herniation. Eur Spine J 2010;19(3):435–438
Mechanical Far Lateral Disc Herniation Reproduction in Ovine Model for Intervertebral Disc Repair
Authors: Friedmann A. , Goehre F. , Schwan S. , Wiesner I. , Meisel H. J.
Published: May 2014

Introduction

Until today, the therapy of intervertebral disc disease is mainly based on the surgical removal of the cartilage tissue that protrudes between the vertebras, as well as the fixation of the vertebral bodies. Thus, the development of regenerative therapies for intervertebral disc degeneration presents a particular research area, which includes both material research and tissue engineering subjects. From a clinical point of view, it is assumed that a self-regenerative implant-based adipose mesenchymal stem cells, combined with an injectable scaffold material, represents a crucial improvement of the mechanical long-term stability of damaged intervertebral disc segments. The objective of the development, evaluation, and testing of the research is to examine various new materials in significant large animal model at several time stages.

Materials and Methods

Because of the similarity in anatomy and biomechanics of the ovine intervertebral disc in comparison to human discs, the sheep animal model was selected. The disc herniation reproduction was performed through a minimal invasive surgery under X-ray control by penetration of the annulus fibrosis with subsequent removal of nucleus pulposus tissue with a Rongeur instrument. After 6 weeks, the induced degeneration of the disc could be observed. This represents the starting point for investigations of suitable materials for intervertebral disc implants. Our study is focused on the development of injectable hydrogels loaded with autologous adipose stem cells.

Results

This model has been used successfully in 33 sheep for injectable scaffold material tests. The procedure and its implication will be presented based on X-ray and micro computed tomography imaging as well as analysis of the disc height.

Conclusion

In cooperation with the BG Hospital Bergmannstrost Halle and Translational Centre for Regenerative Medicine (TRM) Leipzig we developed a suitable sheep animal model with a mechanically induced far lateral disc lesion. Disclosure of Interest None declared
Extended Duration of Torsional Loading Reduces the Survival of Nucleus Pulposus Cells in the Intact Disc
Authors: Chan S. , Walser J. , Ferguson S. J , Gantenbein-Ritter B.
Published: May 2014

Introduction

Previous studies on the influence of torsion and combined torsion-compression loading revealed a positive effect on the cell viability when a repetitive short-term torsion was applied at a physiological magnitude to intervertebral disc organ culture.1 However, after an extended period (8 hours) of combined torsion-compression loading, substantial cell death was detected in the nucleus pulposus (NP).2 In this follow-up study, we aimed to investigate the relationship, if any, between the duration of torsion applied to the intervertebral disc (IVD) and the level of NP cell viability.

Materials and Methods

Bovine caudal discs were harvested and cultured in a custom-built multiaxis dynamic loading bioreactor.2 Torsion (± 2 degrees) was applied to the samples at a frequency of 0.2 Hz. Torsion was applied for durations of 0, 1, 4, and 8 h/d, repeated over 7 days. After the last day of loading, disc tissue was dissected for analysis of cell viability and gene expression.

Results

Disc NP cell viability remained above 85% after torsional loading for 0, 1, or 4 h/d. Viability was statistical significantly reduced to below 70% when torsion was applied for 8 h/d ( p = 0.03) ( Table 1 ). The daily duration of torsional loading did not affect the AF cell viability (> 80% for all loading durations). The trend of collagen 2 gene upregulation and matrix metalloproteases 13 downregulation with an increasing duration of torsion was observed in both NP and AF (Fig. 1). [Table: see text]

Conclusion

We have demonstrated that an extended duration of torsion could inhibit the survival of NP cells within the IVD in organ culture. Acknowledgments Funds from the Orthopedic Department of the Insel University Hospital of Bern and a private donation from Prof. Dr. Paul Heini, Spine Surgeon, Sonnenhof Clinic Bern were received to support this work. Disclosure of Interest None declared References Chan SC, Ferguson SJ, Wuertz K, Gantenbein-Ritter B. Biological response of the intervertebral disc to repetitive short-term cyclic torsion. Spine 2011;36(24):2021–2030 Chan SC, Walser J, Käppeli P, Shamsollahi MJ, Ferguson SJ, Gantenbein-Ritter B. Region specific response of intervertebral disc cells to complex dynamic loading: an organ culture study using a dynamic torsion-compression bioreactor. PLoS ONE 2013;8(8):e72489
17β-Estradiol Protects against Apoptosis Induced by Levofloxacin in Rat Nucleus Pulposus Cells by Upregulating Integrin Alpha2beta1
Authors: Ding W. , Yang S. , Ma L. , Yang D.
Published: May 2014

Introduction

Levofloxacin has been reported to have cytotoxicity to chondrocytes in vitro. 17β-estradiol has been widely studied for its protective effects against cell apoptosis. Based on apoptotic cell model induced by levofloxacin, the purpose of this study was to explore the underlying mechanism by which 17β-estradiol protects rat nucleus pulposus cells from apoptosis.

Materials and Methods

Inverted phase-contrast microscopy, flow cytometry, and caspase-3 activity assay were used to determine apoptosis incidence induced by levofloxacin. Moreover, western blot and real-time quantitative polymerase chain reaction were used to explore the expression of integrins.

Results

Levofloxacin-induced marked apoptosis, which was abolished by 17β-estradiol. Estrogen receptor antagonist, ICI182780, and functional blocking antibody to α2beta1 integrin, both prohibited the effect of 17β-estradiol. Simultaneously, levofloxacin decreased cellular binding ability to type II collagen, which was also reversed by 17β-estradiol. Integrin α2beta1 was responsible for estrogen-dependent anti-apoptosis, which was time- and dose-response effect.

Conclusion

17β-Estradiol was proved for the first time to protect rat nucleus pulposus cells against levofloxacin-induced apoptosis by upregulating integrin α2beta1 signal pathway. Disclosure of Interest None declared
Macrophage Migration Inhibitory Factor Inhibits the Migration of Cartilage End Plate-Derived Stem Cells by Reacting CD74
Authors: Xiong C. , Huang B. , Zhou Y. , Cun Y. , Liu L. , Wang J. , Li C. , Pan Y. , Wang H.
Published: May 2014

Introduction

Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that regulates inflammatory reactions and the pathophysiology of many inflammatory diseases. Intervertebral disc (IVD) degeneration is characterized by an inflammatory reaction, but the potential role of MIF in IVD degeneration has not yet been determined. Recent studies have shown that MIF and its receptor, CD74, are involved in regulating the migration of human mesenchymal stem cells (MSCs). Thus, MIF might impair the ability of mesenchymal stem cells (MSCs) to home to injured tissues. Our previous studies indicated that cartilage endplate-derived stem cells (CESCs) as a type of MSCs exist in human degenerate IVDs. Here, we investigate the role of MIF in regulating the migration of CESCs. Material and Method CESCs were isolated and identified.

Results

We have shown that MIF was distributed in human degenerate IVD tissues and was subject to regulation by the proinflammatory cytokine tumor necrosis factor-α. Furthermore, in-vitro cell migration assays revealed that nucleus pulposus (NP) cells inhibited the migration of CESCs in a number-dependent manner, and enzyme-linked immunosorbent assays revealed that the amount of MIF in conditioned medium was significantly increased as a function of increasing cell number. In addition, recombinant human MIF inhibited the migration of CESCs in a dose-dependent manner. CESCs migration was restored when an antagonist of MIF, (S, R)-3(4-hydroxyphenyl)-4, 5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), was added. Finally, a CD74 activating antibody (CD74Ab) was used to examine the effect of CD74 on CESCs motility and inhibited the migration of CESCs in a dose-dependent manner.

Conclusion

We have identified and characterized a novel regulatory mechanism governing cell migration during IVD degeneration. The results will benefit understanding of another possible mechanism for IVD degeneration, and might provide a new method to repair degenerate IVD by enhancing CESCs migration to degenerated NP tissues to exert their regenerative effects. Disclosure of Interest None declared
Positive Results of Bacterial Culture for Herniated Lumbar Disc-Preliminary Results
Authors: Wu Y. , Li B.
Published: May 2014

Introduction

Recent studies have shown the possibility of involvement of bacterial infection during the intervertebral disc degeneration and low back pain, but there is still controversial. The aim of this study is to investigate whether there is bacterial materials in degenerated intervertebral disc tissues of patients.

Materials and Methods

A total of 20 degenerated intervertebral discs were collected from 16 patients who underwent spinal surgeries, due to disc herniation. Aerobic and anaerobic bacterial cultures were performed for each nucleus pulposus. Ligamentum flavums collected before discectomy were also conducted bacterial cultures for patients with Modic changes.

Results

The disc materials from four patients (six discs) had positive results of microbiological culture. Particles chain bacteria was found in one disc. The sample of two discs of one patient showed coagulase-negative staphylococci. Staphylococcus aureus and coagulase-negative staphylococci were found in another patient. Staphylococcus epidermidis existed in two discs of the same person who had fever after operation. The positive ratio of microbiological culture is 4 out of 16 (25%) patients or 6 out of 20 (30%) discs. All these four individuals had not Modic change.

Conclusion

These results showed the existence of bacteria in the disc materials obtained during back surgeries. These bacteria could be preexisted in the degenerated disc or just from contamination. The differentiation of these two causes is need for further study. Disclosure of Interest None declared References Stirling A, Worthington T, Rafiq M, Lambert PA, Elliott TS. Association between sciatica and Propionibacterium acnes. Lancet 2001;357(9273):2024–2025 Albert HB, Sorensen JS, Christensen BS, Manniche C. Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized clinical controlled trial of efficacy. Eur Spine J 2013;22(4):697–707
Clinical and Radiological Determinant of Surgical Outcome of Lumbar Disc Disease
Authors: Singh P. K.
Published: May 2014

Introduction

Degeneration of lumbar disc is inevitable pathology and its clinical and radiological reflection is extremely variable from patient to patient. Such clinical and radiological heterogeneity of disc degenerative diseases causes variety of surgical dilemma. However, surgical treatment of lumbar degenerative disc disease is mostly individualized approach based. The current research is focused on the clinical and radiological determinant, which can predict the outcome of the patients who are opting for surgical treatment.

Materials and Methods

After Institutional Ethical Committee approval, prospectively 82 cases (age between 18 and 65) of lumbar disc disease has been included in the study who undergone for surgical treatment. Every patient has been evaluated thoroughly clinically and radiologicaly. Postoperative outcome are recorded using modified Oswestry back pain score system and the results were analyzed.

Results

For each patient clinical, demographical, X-ray stress view, and MRI findings are collected and statistically correlated with surgical outcome of the patient. The mean age of the study group 44.3 years. Male gender were predominant 76% of the total sample size. Disc degeneration, facetal arthropathy, Modic changes, and listhesis were high on the list, which determines the outcome of the surgery.

Conclusion

Clincoradiolgical predictors can be taken into account while defining outcome of the surgery of degenerative disc disease. Disclosure of Interest None declared
Diagnosis and Treatment of Degenerative Lumbar Scoliosis with Root Pain
Authors: Liang Y.
Published: May 2014

Introduction

Degenerative lumbar scoliosis is a common type in degenerative lumbar disease. In clinic, root pain is very general except back pain. The objective of our research is to explain and summarize which segments frequently occur root pain, what is the diagnosis methods, and significance of surgical treatment.

Materials and Methods

The research included retrospectively 46 patients suffering degenerative lumbar scoliosis with root pain, undergoing surgical treatment in our hospital during May 2005 to September 2009, all of them have complete follow-up data. The segments of root pain were judged through physical examination, radiography, and selective nerve root injection. According to the the scoliosis type and degree, we chose different surgical procedures, (1) simple decompression, (2) decompression with short segment fixation, (3) decompression and orthopedics with long segment fixation. The patients’ radiographic results were analyzed by X-ray and MRI, functional conditions were evaluated by Oswestry disability index (ODI) and visual analog scale (VAS).

Results

The research included 46 patients, the average follow-up was 5.8 years. Male patients were 20, and female patients were 26 in our research. According to segments of root pain: L2-3 (4 patients), L3-4 (9 patients), L4-5 (21 patients), L5-S1 (12 patients); surgical procedures: simple decompression (4 patients), decompression with short segment fixation (35 patients), decompression and orthopedics with long segment fixation (7 patients). A total of 42 patients had bony fusion by radiography. In scoliosis orthopedics group, the cobb angle dropped from 19.3 ± 15.2 degrees preoperatively to 9.2 ± 5.3 degrees at final follow-up. ODI of all patients dropped from 59.22 ± 22.31 preoperatively to 15.23 ± 11.12; and VAS dropped from 7.3 ± 1.8 to 2.3 ± 1.4 at final follow-up, respectively.

Conclusion

(1) Root pain of degenerative lumbar scoliosis usually located to the segment, which just under the bulge side (39/46, 84.8%), rather than concave side. (2) Radiography and selective nerve root injection were helpful to ensure the pain segment and position. (3) Most degenerative lumbar scoliosis patients undergoing root pain can proceed simple decompression or decompression with short segment fixation, only few patients need to proceed decompression and orthopedics with long segment fixation. Disclosure of Interest None declared