Aims. This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of
Aims. Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of
Aims. In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in
Objectives. Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human
Using deep learning and image processing technology, a standardized automatic quantitative analysis systerm of lumbar disc degeneration based on T2MRI is proposed to help doctors evaluate the prognosis of
Purpose of study and background. Clinical researchers use Pfirrmann classification for grading
Current therapies for
It has been proposed that
Biomechanical overloading initiates
Introduction: Osteoporotic fractures affect certain bones more than others, suggesting that systemic bone loss is not the only underlying cause. We have shown that age-related
Low back pain affects 80% of the population with half of cases attributed to
Background. The association between lumbar
Purpose of study and background. Mechanical overloading initiates
Back pain is a leading cause of disability worldwide and it is primarily considered to be triggered by
Introduction.
Mesenchymal stem cells (MSCs) are exciting candidates for cellular repopulation and repair in
Purpose of study and background. Low back pain affects 80% of the population at some point in their lives with 40% of cases attributed to
Background.
Background. Endplate defect is an MRI trait, found to be associated with
Degenerative disc disease (DDD) is a common cause of lower back pain. Calcification of the intervertebral disc (IVD) has been correlated with DDD, and is especially prevalent in scoliotic discs. The appearance of calcium deposits has been shown to increase with age, and its occurrence has been associated with several other disorders such as hyperparathyroidism, chondrocalcinosis, and arthritis. Trauma, vertebral fusion and infection have also been shown to increase the incidence of IVD calcification. Our data indicate that Ca2+ and expression of the extracellular calcium-sensing receptor (CaSR) are significantly increased in mild to severely degenerative human IVDs. In this study, we evaluated the effects of Ca2+ and CaSR on the degeneration and calcification of IVDs. Human donor lumbar spines of Thompson grade 2, 3 and 4 through organ donations within 24 hs after death. IVD cells, NP and AF, were isolated from tissue by sequential digestion with Pronase followed by Collagenase. Cells were expanded for 7 days under standard cell culture conditions. Immunohistochemistry was performed on IVD tissue to validate the grade and expression of CaSR. Free calcium levels were also measured and compared between grades. Immunocytochemistry, Western blotting and RT-qPCR were performed on cultured NP and AF cells to demonstrate expression of CaSR, matrix proteins aggrecan and collagen, catabolic enzymes and calcification markers. IVD cells were cultured in increasing concentrations of Ca2+ [1.0-5.0 mM], CaSR allosteric agonist (cincalcet, 1 uM), and IL-1b [5 ng/mL] for 7 days. Ex vivo IVD organ cultures were prepared using PrimeGrowth Disc Isolation System (Wisent Bioproducts, Montreal, Quebec). IVDs were cultured in 1.0, 2.5 mM Ca2+ or with cinacalcet for 21 days to determine effects on disc degeneration, calcification and biomechanics. Complex modulus and structural stiffness of disc tissues was determined using the MACH-1 mechanical testing system (Biomomentum, Laval, Quebec). Ca2+ dose-dependently decreased matrix protein synthesis of proteoglycan and Col II in NP and AF cells, similar to treatment with IL-1b. (n = 4). Contrarily to IL-1b, Ca2+ and cincalcet did not significantly increase the expression of catabolic enzymes save ADAMTS5. Similar effects were observed in whole organ cultures, as Ca2+ and cinacalcet decreased proteoglycan and collagen content. Although both Ca2+ and cinacalcet increased the expression of alkaline phosphatase (ALP), only in Ca2+-treated IVDs was there evidence of calcium deposits in NP and AF tissues as determined by von Kossa staining. Biomechanical studies on Ca2+ and cinacalcet-treated IVDs demonstrated decreases in complex modulus (p<0.01 and p<0.001, respectively; n=5), however, only Ca2+-treated IVDs was there significant increases stiffness in NP and AF tissues (p<0.001 and p<0.05, respectively; n=3). Our results suggest that changes in the local concentrations of calcium and activation of CaSR affects matrix protein synthesis, calcification and IVD biomechanics. Ca2+ may be a contributing factor in IVD degeneration and calcification.
A key cause of low back pain is the degeneration of the intervertebral disc (IVD). Causality between infection of the IVD and its degenerative process gained great interest over the last decade. Granville Smith et al. (2021) identified 36 articles from 34 research studies investigating bacteria in human IVDs. Bacteria was identified in 27 studies, whereas 9 attributed bacterial presence to contamination. Immunohistochemical staining for Gram positive bacteria was performed on human IVD tissue to identify presence and characterise bacterial species. Nucleus pulposus (NP) cells in monolayer and 3D alginate were stimulated with LPS and Peptidoglycan (0.1-50 µg/ml) for 48hrs. Following stimulation qPCR for factors associated with disc degeneration including matrix genes, matrix degrading enzymes, cytokines, neurotrophic factors and angiogenic factors and conditioned media collected for ELISA and luminex analysis Gram positive bacteria was detected within human IVD tissue. Internalisation of bacteria by NP cells influenced the cell and nuclei morphology. Preliminary results of exposure of NP cells to bacterial components indicate that LPS as well as Peptidoglycan increase IL-8 and ADAMTS-4 gene expression following 48 hours of stimulation with a dose response seen for IL-8 induction by peptidoglycan compared to the control group. Underlining these results, IL-8 protein release was increased for treated groups compared to non-treated control. Further analysis is underway investigating other output measures and additional biological repeats. This study has demonstrated bacteria are present within IVD cells within IVD tissue removed from degenerate IVD and is determining the potential influence of these on disc degeneration.
Low back pain is strongly associated with degeneration of the intervertebral disc (IVD). During degeneration, altered matrix synthesis and increased matrix degradation, together with accompanied cell loss is seen particularly in the nucleus pulposus (NP). It has been proposed that notochordal (NC) cells, embryonic precursors for the cells within the NP, could be utilized for mediating IVD regeneration. However, injectable biomaterials are likely to be required to support their phenotype and viability within the degenerate IVD. Therefore, viability and phenotype of NC cells were analysed and compared within biomaterial carriers subjected to physiological oxygen conditions over a four-week period were investigated. Porcine NC cells were incorporated into three injectable hydrogels: NPgel (a L-pNIPAM-co-DMAc hydrogel), NPgel with decellularized NC-matrix powder (dNCM) and Albugel (an albumin/ hyaluronan hydrogel). The NCs and biomaterials constructs were cultured for up to four weeks under 5% oxygen (n=3 biological repeats). Histological, immunohistochemical and glycosaminoglycans (GAG) analysis were performed to investigate NC viability, phenotype and extracellular matrix synthesis and deposition.Objectives
Methodology
Low back pain is strongly associated with degeneration of the intervertebral disc (IVD). During degeneration, altered matrix synthesis and increased matrix degradation, together with accompanied cell loss is seen particularly in the nucleus pulposus (NP). It has been proposed that notochordal (NC) cells, embryonic precursors for the cells within the NP, could be utilized for mediating IVD regeneration. However, injectable biomaterials are likely to be required to support their phenotype and viability within the degenerate IVD. Therefore, viability and phenotype of NC cells were analysed and compared within biomaterial carriers subjected to physiological oxygen conditions over a four-week period were investigated. Porcine NC cells were incorporated into three injectable hydrogels: NPgel (a L-pNIPAM-co-DMAc hydrogel), NPgel with decellularized NC-matrix powder (dNCM) and Albugel (an albumin/ hyaluronan hydrogel). The NCs and biomaterials constructs were cultured for up to four weeks under 5% oxygen (n=3 biological repeats). Histological, immunohistochemical and glycosaminoglycans (GAG) analysis were performed to investigate NC viability, phenotype and extracellular matrix synthesis and deposition. Histological analysis revealed that NCs survive in the biomaterials after four weeks and maintained cell clustering in NPgel, Albugel and dNCM/NPgel with maintenance of morphology and low caspase 3 staining. NPgel and Albugel maintained NC cell markers (brachyury and cytokeratin 8/18/19) and extracellular matrix (collagen type II and aggrecan). Whilst Brachyury and Cytokeratin were decreased in dNCM/NPgel biomaterials, Aggrecan and Collagen type II was seen in acellular and NC containing dNCM/NPgel materials. NC containing constructs excreted more GAGs over the four weeks than the acellular controls. NC cells maintain their phenotype and characteristic features in vitro when encapsulated into biomaterials. NC cells and biomaterial construct could potentially become a therapy to treat and regenerate the IVD.
Purpose:
The purpose of this study was to investigate the possible relationship between matrix metalloproteinase-3 (MMP-3) promoter 5A/6A polymorphism and
Introduction:
Current medical treatments for IVD degeneration rely on conservative therapies or surgery. Surgical treatments (e.g. spinal fusion,) have shown satisfactory results in alleviating pain, but long-term clinical outcomes remain poor. Thus, there is an urgent need for alternative cell based regenerative therapies focussed on correcting the underlying pathogenesis of IVD degeneration. However, for these to be successful an appropriate cell source for implantation, together with a suitable growth factor to direct cell differentiation and formation of a functional matrix must be identified. Additionally, extensive
Injectable hydrogels via minimally invasive surgery reduce the risk of infection, scar formation and the cost of treatment. Degradation of the intervertebral disc (IVD) currently has no preventative treatment. An injectable hydrogel material could restore disc height, reinforce local mechanical properties, and promote tissue regeneration. We present a hydrogel material Laponite® associated poly(N-isopropylacrylamide)-co-poly(dimethylacrylamide) (NPGel). Understanding how the components of this hydrogel system influence material properties, is crucial for tailoring treatment strategies for the IVD and other tissues. The effect of hydrogel wt./wt., clay and co-monomer percentages were assessed using a box-Behnken design. Rheometry, SEM, FTIR and swelling was used to measure changes in material properties in simulated physiological conditions. Rheometry revealed gelation temperature of hydrogel materials could be modified with dimethyl-acrylamide co-monomer; however, final maximum mechanical properties remained unaffected. Increasing the weight % and clay % increased resultant mechanical properties from ∼500–2500 G' (Pa), increased viscosity, but retained the ability to flow through a 26G needle at 39°C.Introduction
Methods & Results
Mesenchymal stem cells (MSCs) are undergoing evaluation as a potential new therapy for immune and inflammatory-mediated conditions such as IVD degeneration (IDD). Both adipose (ASCs) and bone-marrow (BMSCs) derived MSCs have been widely used in this regard. The optimal tissue source and expansion conditions required to exploit the regenerative capacity of these cells are not yet fully elucidated. In addition the phenotypic response of transplanted cells to the disease environment is not well understood. In this study, ASCs and BMSCs were exposed to a combination of hypoxic conditioning and selected inflammatory mediators, conditions that mimic the microenvironment of the degenerate IVD, in an effort to understand their therapeutic potency for Donor-matched ASCs and MSCs were pre-conditioned with either IL-1β (10ng/ml) or TNFα (10ng/ml) for 48 hours under hypoxic conditions (5% O2). Conditioned media was collected and 45 different immunomodulatory proteins were analysed using human magnetic Luminex® assay. Secreted levels of several key cytokines and chemokines, both pro- and anti-inflammatory, were significantly upregulated in ASCs and BMSCs following the conditioning regime. Under all conditions tested, ASCs expressed significantly higher levels of IL-4, IL-6, IL-10, IL-12, TGF-α, and GCSF compared to BMSCs. Pre-conditioning with TNFα resulted in significantly higher levels of IL-10 while preconditioning with IL-1β resulted in higher levels of IL-6, IL-12 and GCSF.Background
Methods and Results
Our study establishes a rabbit model of disc degeneration which requires neither a chemical nor physical injury to the disc. Disc degeneration similar to that seen in man was created at levels proximal (L4-L5) and caudal (L7-S1) to a simulated lumbar fusion and was studied for up to nine months after arthrodesis. Loss of the normal parallel arrangement of collagen bundles within the annular lamellae was observed in intervertebral discs adjacent to the fusion at three months. By six months there was further disorganisation as well as loss of distinction between the lamellae themselves. By nine months the structure of the disc had been replaced by disorganised fibrous tissue, and annular tears were seen. There was an initial cellular proliferative response followed by loss of chondrocytes and notochordal cells in the nucleus pulposus. Degeneration was accompanied by a decrease in the monomer size of proteoglycans. Narrowing of the disc space, endplate sclerosis and the formation of osteophytes at adjacent disc spaces were observed radiologically.
Intervertebral discs (IVDs) are fibrocartilagenous ovoids located between the vertebral bodies of the spine that provide the sole source of flexibility in that structure. IVDs are clinically very important as degeneration has been shown to be strongly associated with lower back pain, sciatica, and disc herniation: potentially disabling conditions that affect a very large section of the UK population. The aetiology of disc degeneration is poorly understood although upregulation of matrix metalloproteinase (MMP) activity is thought to be involved. Degradation products of the extra-cellular matrix are known to increase MMP production and activity in other tissues. This project concentrated on examining the effects of degredation products of elastin. Elastin fragments (κ-elastin peptides) have been shown to upregulate mRNA levels and increase expression of pro-MMP-1 in human skin fibroblasts, cells that are thought to be similar to those residing in the annulus fibrosus of intervertebral discs. This study examined their effect on disc cells and on skin fibroblasts. Total MMP-2 and -7 activity produced by cells extracted from the annulus fibrosus of bovine intervertebral disc cells and cultured for 24 hours with 0–300μg/ml κ-elastin was determined using fluorimetric and zymographic analyses. κ-elastin was prepared from bovine ligamentum nuchae or bovine intervertebral discs. Culture with κ-elastin prepared from bovine ligamentum nuchae caused skin and disc cell potential pro-MMP-2 activity to increase in a dose-dependent manner; the potential pro-MMP-2 activity of both cell types is more than doubled when cultured with 300μg/ml κ-elastin. These findings suggest that in the bovine disc, matrix breakdown may cause a feedback loop with degraded elastin stimulating disc cells to increase production of pro-MMP-2, with the possibility of further degrading elastin and other proteins and contributing to IVD breakdown.
We studied 52 patients, each with a lumbosacral transitional vertebra. Using MRI we found that the lumbar discs immediately above the transitional vertebra were significantly more degenerative and those between the transitional vertebrae and the sacrum were significantly less degenerative compared with discs at other levels. We also performed an anatomical study using 70 cadavers. We found that the iliolumbar ligament at the level immediately above the transitional vertebra was thinner and weaker than it was in cadavers without a lumbosacral transitional vertebra. Instability of the vertebral segment above the transitional vertebra because of a weak iliolumbar ligament could lead to subsequent disc degeneration which may occur earlier than at other disc levels. Some stability between the transitional vertebra and the sacrum could be preserved by the formation of either an articulation or by bony union between the vertebra and the sacrum through its transverse process. This may protect the disc from further degeneration in the long term.
T2D is postulated to be an important aetiological factor for lumbar disc degeneration (LDD), which itself has a well documented relationship with low back pain. Obesity increases risk of both T2D, low back pain and LDD. Connective tissue modification has been reported in hyperglycaemia, but the epidemiology of LDD in T2D has not been described to date. A population sample of unselected same-sex adult twin pairs was studied who had attended a spine MR study and completed general health questionnaires defining T2D by self-report. LDD had been coded as the sum of five lumbar discs coded (0–3) for each of height, signal intensity, disc bulge and anterior osteophytes. Risk factors for LDD included age, body-mass index (BMI), sex, alcohol consumption and smoking. Mean age of the 1011 participants = 54 years (sd=8), mean BMI=25 kg/m2 (sd=4), 95% female. The prevalence of T2D was 6%. Twins with T2D had increased BMI (27 vs 25 kg/m2, p<0.001) and were older (59 vs 54 years, p<0.001). LDD score in T2D was significantly higher in diabetic cases than controls (14.9 vs 13.1, p=0.04) in univariable analysis. In multivariable analysis inclusion of age and BMI abrogated the effect of T2D.Background and aims:
Methods and results:
Current strategies to treat back pain address the symptoms but not the underlying cause. Here we are investigating a novel hydrogel material (NPgel) which can promote MSC differentiation to Nucleus pulposus cells. Current hMSCs were encapsulated in NPgel and cultured for 4 weeks under hypoxia (5%) with ± calcium (2.5mM and 5.0mM CaCl2), IL-1β and TNFα either individually or in combination to mimic the degenerate microenvironment. Cell viability was assessed by Alamar blue assay. Histological and immunohistochemical analysis investigated altered matrix and matrix degrading enzyme expression.Introduction
Methods
Degenerate disc disease is a major cause of low back pain, yet its aetiology is still poorly understood. The intervertebral disc is the largest avascular structure in the body. Cells of the nucleus pulposus, therefore, rely on diffusion of oxygen &
nutrients down concentration gradients from peripheral vessels in the cartilage end-plates. Thus, there is a low oxygen tension and cellular respiration is largely anaerobic. The purpose of this study was to examine the effects of inflammation, hypoxia and acidosis on degeneration and pro-inflammatory mediator production in virgin porcine nucleus pulposus cultures. Intervertebral discs were harvested from normal 6-month old agricultural pigs slaughtered for other purposes. Nucleus pulposus was contained within the annulus until further dissection under sterile conditions in the laboratory was performed. Nucleus pulposus was harvested, diced and divided into 200mg samples. Samples were incubated under optimal conditions. Discs were cultured in 5μg/ml E. coli lipopolysaccharide, in a hypoxic environment or at low pH. IL-6, IL-8 and LDH assays were performed by ELISA, in accordance with manufacturer’s instructions. Time and dose-response curves were generated for each experiment (results not shown). Results at 72 hours incubation are tabulated below: These results confirm that nucleus pulposus is a biochemically active tissue capable of producing pro-inflammatory mediators in response to environmental stresses. IL-6 and IL-8 are both involved in the inflammatory cascade, causing chemotaxis of neutrophils and macrophages to the area. IL-8 itself causes hyperalgesia. Acidotic and inflammatory conditions, but not hypoxia, stimulated cytokine release. This may indicate a protective reduction in cellular activity in reduced oxygen environments. Necrosis, as measured by LDH production, was negligible.
Anatomisches Institut der Georg-August-Universität Göttingen, Germany Biomedical Research Centre, Dept. of Orthopaedic Surgery, Academic Hospital, Pretoria, South Africa To date, no animal model for disc degeneration has gained much acceptance, mostly due to the fact that most animals are quadrupeds and thus lack basic biomechanical characteristics of human spines. An adequate model would be of invaluable interest for degeneration related research. In a standardized series of animal experiments in 18 adult Minipigs and 20 adult Cercopithecus aethiops monkeys all animals obtained nucleotomy in one lumbar FSU from a ret-roperitoneal approach and were sacrificed at last 24 weeks afterwards. The Minipigs were x-rayed at time of sacrifice, the monkeys prior to operation and at termination of the experiment. Vice versa, the Minipigs obtained intradiscal pressure recordings at these occasions. The Minipig spines were formol fixed whereas the monkey spines were harvested after perfusion with PBS, fresh frozen, and obtained CT and MRI scans prior to thawing, fixation and comprehensive histological evaluation. The lumbar FSU of Minipig and Cercopithecus mainly consists of the same elements as in man. There are certain differences concerning the porcine endplates which ossify as an epiphyseal-like formation with ossification starting in its center, different from the so-called “Randleiste”. Whereas the operative procedure in the Minipigs came in handy, in the Cercopithecus monkey it proved to be demanding, though feasible, due to relatively wide transverse processes and thick psoas muscle structures. The psoas could not be easily detached and needed to be split instead, thus directly exposing the segment nerves. The histological, standard radiological, CT, MRI, and mechanical observations were very similar to those which can be made during the natural aging process of the disc in man. Both animal models are recommendable for further research: Cercopithecus FSUs are more difficult to expose. Logistic reasons may favour Minipigs in Europe. In case of fusion related experiments the use of primates yet seems inevitable.
We attempted to correlate the findings of MRI and discography in patients with low back pain, examining 108 lumbar intervertebral discs in 33 consecutive patients. MRI results were assessed from the intensity and shape of the signal obtained from the central part of the disc. Discography was classified according to the pattern of contrast material, the pressure accepted and the pain reproduced. All discs which were abnormal on MRI had altered patterns on discography, but 18 of the 60 discs with normal MRI had abnormal discograms. Of 39 asymptomatic discs, 33 had normal MRI signals and 24 had normal discograms. None of the 15 discs showing severe degeneration on MRI sustained high levels of intradiscal pressure, but only six of the 60 discs giving normal MRI had low pressure. With current techniques, discography is more accurate than MRI for the detection of annular pathology: a normal MRI does not exclude significant changes in the peripheral structure of the intervertebral disc which can produce low back pain.
For phase angle (approximate magnitude 5°), no significant overall effects due to degeneration were found across any loading direction (P>
0.2). ANOVA analyses on maximum/minimum principal strains found no significant effect due to disc grade (P>
0.063). However, a small number of significant effects due to disc grade were found at particular strain gauge locations for the isolated disc in flexion, the intact FSU in extension, and the intact FSU/isolated disc in right lateral bending.
The non-significant small phase angles suggest that the disc behaves more like an elastic solid than a poroelastic material, and that dehydration associated with degeneration does not adversely affect damping. Principal strains were not significantly affected by disc degeneration overall, suggesting that the cortical shell adjacent to the disc-endplate boundary maintains a relatively homeostatic condition, with more dramatic architectural changes probably occurring within the trabecular bone. Applications of this research include providing important validation data for analytical/finite element models of the intact FSU and isolated disc segment, and a better understanding of the magnitudes of cortical strains that need to be maintained in order to avoid damaging vertebral bone stress-shielding effects after treatments for disc degeneration.
Disc degeneration is often scored using macroscopic and microscopic scoring systems. Although reproducible, these scores may not accurately reflect declining function in a degenerated disc. Accordingly, we compared macroscopic and microscopic degeneration scores with measurements of disc function. Thirteen cadaveric motion segments (62–93 yrs) were compressed to 1kN while a pressure-transducer was pulled across the mid-sagittal diameter of the disc. Resulting stress profiles indicated intradiscal pressure (IDP), and maximum stress in the anterior (MaxStress_Ant) and posterior (MaxStress_Post) annulus. Macroscopic Introduction
Methods
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. Cite this article:
The presence of facet tropism has been correlated with an elevated susceptibility to lumbar disc pathology. Our objective was to evaluate the impact of facet tropism on chronic lumbosacral discogenic pain through the analysis of clinical data and finite element modelling (FEM). Retrospective analysis was conducted on clinical data, with a specific focus on the spinal units displaying facet tropism, utilizing FEM analysis for motion simulation. We studied 318 intervertebral levels in 156 patients who had undergone provocation discography. Significant predictors of clinical findings were identified by univariate and multivariate analyses. Loading conditions were applied in FEM simulations to mimic biomechanical effects on intervertebral discs, focusing on maximal displacement and intradiscal pressures, gauged through alterations in disc morphology and physical stress.Aims
Methods
Cite this article:
In the last decades, the use of artificial intelligence (AI) has been increasingly investigated in
Monomeric C reactive protein (mCRP) presents important proinflammatory effects in endothelial cells, leukocytes, or chondrocytes. However, CRP in its pentameric form exhibits weak anti-inflammatory activity. It is used as a biomarker to follow severity and progression in infectious or inflammatory diseases, such as
Tryfonidou leads the Horizon 2020 consortium (iPSpine; 2019–2023) bringing a transdisciplinary team of 21 partners together to address the challenges and bottlenecks of iPS-based advanced therapies towards their transition to the clinic. Here, chronic back pain due to
Background.
Aims. Inflammatory response plays a pivotal role in the pathophysiological process of
Low back pain (LBP) is the main cause of disability worldwide and is primarily triggered by
Despite promising results in attempting intervertebral disc regeneration, intradiscal cell transplantation is affected by several drawbacks, including poor viability in the harsh disc environment, low cost-effectiveness, and immunogenic/tumorigenic concerns. Recently, the development of cell-free approaches is gaining increasing interest in the field, with a particular regard towards extracellular vesicles (EVs). Nucleus pulposus cell (NPC) progenitors characterized by Tie2 expression have shown a higher chondrogenic differentiation potential compared to MSCs. The aim of this study was to investigate the putative regenerative effects of EVs isolated from Tie2-overexpressing NPC progenitors on degenerative NPCs. NPCs were isolated from young donors and underwent an optimized culture protocol to maximize Tie2 expression (NPCs. Tie2+. ) or a standard protocol (NPCs. STD. ). Following EV characterization, NPC isolated from patients affected by
Objectives. This study aims to investigate whether bacteria are present in intervertebral discs (IVDs) and their influence. Causality between chronic infection of the IVD and its degenerative process gained great interest recently. Granville Smith et al. (2021) identified 36 articles from 34 research studies investigating bacteria in IVDs, from these 27 studies found, Cutibacterium acnes being the most abundant. However, whether bacteria identified were present in vivo or if they represent contamination remains unclear. Methods. Human IVD tissue was fixed in paraffin and Immunohistochemical stained for Gram-positive bacteria. NP cells in monolayer have been stimulated with LPS (0.1–50 µg/ml) and Peptidoglycan (0.1–50 µg/ml) for 24, 48 and 72 hrs to investigate their influence. The concentration of proinflammatory and catabolic cytokines in the media is being measured using ELISA. RNA extracted and RT-qPCR utilised for factors associated with disc degeneration matrix genes, matrix degrading enzymes, cytokines, neurotrophic factors and angiogenic factors. Results. Bacteria were detected within IVD tissue. Bacteria was internalized by the NP cells and influenced the nuclei morphology. Preliminary results of the exposure of NP cells to bacterial components demonstrate that ADAMTS4 as well as IL-8 were showed an increase in gene expression after LPS and peptidoglycan treatment compared to the non-treated control. Underlining these results, IL-8 protein was increased in treated groups, whereas peptidoglycan treated groups showed a dose dependence. Conclusion. This study demonstrates that Gram positive bacteria are present within the IVD. The exposure of NP cells to peptidoglycans indicates that bacterial components trigger a stress response. Conflicts of Interest: No conflict of interest. Sources of Funding: This project is part of the Disc4All Training network to advance integrated computational simulations in translational medicine, applies to
Introduction. Multiple studies have identified Cutibacterium acnes (C.acnes) and other microbes in intervertebral disc tissue using 16S DNA Sequencing and microbial cultures. However, it remains unclear whether these bacteria are native to the discs or result from perioperative contamination. Our study aimed to detect Gram-positive bacteria in non-herniated human disc samples and explore correlations with Toll-like receptors (TLR) 2, TLR4, NLRP3, and Gasdermin D. Methods. Immunohistochemical staining was conducted on 75 human IVD samples for Gram-positive bacteria, S. aureus, C.acnes, TLR2, TLR4, NLRP3, and Gasdermin D. Cell detection and classification were performed using QuPath. NP cells were treated with Lipopolysaccharide (LPS) and Peptidoglycan (PGN) in monolayer and alginate beads for up to 72 hours, followed by secretome analysis using Luminex. Statistical analysis included Kruskal-Wallis, Dunn's multiple comparison test, and Pearson correlation. Results. Immunohistochemical staining revealed Gram-positive bacteria exclusively within cells, with C. acnes positivity ranging from 5–99% and correlating with patient age (r=0.41, p= 0.007). TLR2 positivity ranged from 5–99% and TLR4 from 3–72%, showing a strong correlation (r= 0.62, p= 1.5e-006). Females with mid-degenerative grades exhibited significantly decreased TLR2 expression compared to those without degeneration signs. Treatment with LPS and PGN increased catabolic cyto- and chemokines associated with IVD degeneration. Conclusion. In conclusion, this study confirms Gram-positive bacteria presence in non-herniated human disc samples and highlights their role in triggering a catabolic response in disc cells. No conflicts of interest. . Sources of funding. This project is part of the Disc4All Training network to advance integrated computational simulations in translational medicine, applies to
Osteoarthritis (OA) is a painful and disabling chronic condition that constitutes a major challenge to health care worldwide. There is currently no cure for OA and the analgesic pharmaceuticals available do not offer adequate and sustained pain relief, often being associated with significant undesirable side effects. Another disease associated with degenerating joints is
Introduction and Objective. Low back pain (LBP) is a disorder strongly associated with
Introduction: Age-related hormonal changes and inactivity lead to systemic bone loss and osteoporotic fractures. However, it is not clear why the vertebral body should be affected so often, or why its anterior region should characteristically sustain a “wedge” deformity. We hypothesise that
The use of stem cells transplanted into the intervertebral disc (IVD) is a promising regenerative approach to treat
In our study, the aims were to describe the changes in the appearance of the lumbar spine on MRI in elite fast bowlers during a follow-up period of one year, and to determine whether these could be used to predict the presence of a stress fracture of the posterior elements. We recruited 28 elite fast bowlers with a mean age of 19 years (16 to 24) who were training and playing competitively at the start of the study. They underwent baseline MRI (season 1) and further scanning (season 2) after one year to assess the appearance of the lumbar intervertebral discs and posterior bony elements. The incidence of low back pain and the amount of playing and training time lost were also recorded. In total, 15 of the 28 participants (53.6%) showed signs of acute bone stress on either the season 1 or season 2 MR scans and there was a strong correlation between these findings and the later development of a stress fracture (p <
0.001). The prevalence of
Mesenchymal stem-cell based therapies have been
proposed as novel treatments for
Backgrounds and aim. Low back pain resulting from
Objective. Modic changes (MC) is a form of
Objective. Modic changes (MC), a form of
Low back pain is thought to relate to
Background.
Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive. Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis.Aims
Methods
Introduction and Objective. Low back pain (LBP) is a major cause of long-term disability in adults worldwide and it is frequently attributed to
Introduction and Objective.
Introduction and Objective.
Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease. We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.Aims
Methods
Abstract. Objectives. Back pain will be experienced by 70–85% of all people at some point in their lives and is linked with
This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect. This experiment included three patients diagnosed with lumbar disc herniation who failed conservative treatment. Nucleus pulposus tissue was isolated from these patients when they underwent surgical intervention, and primary NPCs were isolated and cultured. Western blotting, reverse transcription polymerase chain reaction, fluorescence staining, and other methods were used to detect changes in related signalling pathways and the ability of cells to resist pyroptosis.Aims
Methods
Introduction. Decreasing endplate porosity has been proposed as a risk factor for
The action of fast bowling in the game of cricket is known to cause injuries to the lumbar spine. We studied a group of 16- to 18-year-old fast bowlers, selected for special training in Western Australia. All 24 had MR scans of the spine, 22 had radiographs and CT scans; in 20 the bowling technique was analysed biomechanically. There was a high incidence of back pain and this was always associated with a radiological abnormality. Pars interarticularis defects were diagnosed in 54% and
The pathophysiology of
1. At the present stage of our experience, when 150 patients have been analysed over a period of five years, the conclusion has been reached that anterior interbody fusion in the lower lumbar spine is a procedure which should be added to our surgical armamentarium for use in selected cases. 2. Patients suffering from chronic
Study purpose and background. Novel regenerative therapies have the potential to restore function and relieve pain in patients with low back pain (LBP) caused by
Background.
The safety of nucleus implants remains an open issue in the treatment of
Introduction: Modic changes are vertebral endplate changes visible in magnetic resonance imaging (MRI), which associate with degenerative intervertebral disc disease. Twin studies suggest that
Aims: As inflammation plays a key role in the etiology of
Background and Purpose.
Low back pain is more common in women than men, yet most studies of
Background: The epidemiology of Schmorl nodes is based on post-mortem investigations. The proposed pathogenesis of the focal nodes is a bulging of the disc into the vertebral body depending of the degree of osteoporosis. Secondar peripheral osteophytes are formed at the annular insertion. Study design: A cross sectional epidemiological study of 4151 participants of the Copenhagen Osteoarthritis Study in 1993 with a 13 years follow with the Roland-Morris (R-MQ) back pain questionnaire. In 1993 standardized, lateral radiographs of the lumbar spine were recorded and the bone mineral density (BMD) was estimated by digital x-ray radiogrammetry of standardised hand x-rays. Methods: Statistical correlations were made between Schmorl nodes and low back pain in 1993, the R-MQ score, BMD and the presence of osteophytes, disc degeneration and endplate sclerosis. Results: There were 2610 women and 1538 men. At follow up 1190 women and 674 responded. In 196 cases one or more Schmorl nodes in the lumbar spine were found (women 3.7 %, men 6.5 %). A decreasing prevalence of Schmorl nodes by ages was found in both genders (p<
0.000). At the time of the radiographic examination participants with Schmorl nodes clamed of low back pain (p=0.003). The presence of nodes was without relation to osteophytosis,
Aims: Recent advances in our understanding of intervertebral disc biology have led to develop novel treatments for
1. In this series of posterior onlay grafting with fresh autogenous bone and without internal fixation, in the treatment of non-infective structural lesions in the lumbo-sacral area, 71 per cent of the patients were relieved of their symptoms, but bony fusion was obtained in only 60 per cent. 2. It is probable that with this technique twelve weeks' immobilisation in a plaster bed is required. 3. Some failures are ascribed to the use of an insufficient quantity of bone or to poor apposition of the graft to its bed. 4. It is evident that the more vertebrae one attempts to fuse the more difficult it is to succeed. When the diseased area is successfully fused but an unnecessarily long graft has been used, a pseudarthrosis above the level of the pre-operative pathology may be the cause of persisting backache. For these reasons we believe that one should not attempt to graft more vertebrae than is necessary to stabilise the local lesion. 5. The complication rate, particularly from deep vein thrombosis, was high. This major complication could perhaps be overcome by using banked bone. 6. The indications for the operation are assessed as follows. It should be done for low back pain only when there is a definite diagnosis and a limited extent of structural pathology; one can then expect excellent results when successful fusion is achieved and also an appreciably high proportion of satisfied patients even when bony fusion has not been obtained, presumably because there is a fibrous union strong enough to stabilise the affected spine. It is inadvisable to undertake lumbar-lumbo-sacral fusion for
Summary Statement. Conventional imaging techniques lack the ability to objectively assess early stages of