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
In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD. An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD.Aims
Methods
This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD). The gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.Aims
Methods
Cite this article:
Aims. CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration. Methods. We investigated the effects of mCRP and the signalling pathways that are involved in cultured human primary
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
The aim of the study was to determine if there was a direct correlation between the pain and disability experienced by patients and size of their disc prolapse, measured by the disc’s cross-sectional area on T2 axial MRI scans. Patients were asked to prospectively complete visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores on the day of their MRI scan. All patients with primary disc herniation were included. Exclusion criteria included recurrent disc herniation, cauda equina syndrome, or any other associated spinal pathology. T2 weighted MRI scans were reviewed on picture archiving and communications software. The T2 axial image showing the disc protrusion with the largest cross sectional area was used for measurements. The area of the disc and canal were measured at this level. The size of the disc was measured as a percentage of the cross-sectional area of the spinal canal on the chosen image. The VAS leg pain and ODI scores were each correlated with the size of the disc using the Pearson correlation coefficient (PCC). Intraobserver reliability for MRI measurement was assessed using the interclass correlation coefficient (ICC). We assessed if the position of the disc prolapse (central, lateral recess, or foraminal) altered the symptoms described by the patient. The VAS and ODI scores from central and lateral recess disc prolapses were compared.Aims
Methods
Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining.Aims
Methods
The aim of this study was to determine the differences in spinal imaging characteristics between subjects with or without lumbar developmental spinal stenosis (DSS) in a population-based cohort. This was a radiological analysis of 2,387 participants who underwent L1-S1 MRI. Means and ranges were calculated for age, sex, BMI, and MRI measurements. Anteroposterior (AP) vertebral canal diameters were used to differentiate those with DSS from controls. Other imaging parameters included vertebral body dimensions, spinal canal dimensions, disc degeneration scores, and facet joint orientation. Mann-Whitney U and chi-squared tests were conducted to search for measurement differences between those with DSS and controls. In order to identify possible associations between DSS and MRI parameters, those who were statistically significant in the univariate binary logistic regression were included in a multivariate stepwise logistic regression after adjusting for demographics. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported where appropriate.Aims
Methods
To study the associations of lumbar developmental spinal stenosis (DSS) with low back pain (LBP), radicular leg pain, and disability. This was a cross-sectional study of 2,206 subjects along with L1-S1 axial and sagittal MRI. Clinical and radiological information regarding their demographics, workload, smoking habits, anteroposterior (AP) vertebral canal diameter, spondylolisthesis, and MRI changes were evaluated. Mann-Whitney U tests and chi-squared tests were conducted to search for differences between subjects with and without DSS. Associations of LBP and radicular pain reported within one month (30 days) and one year (365 days) of the MRI, with clinical and radiological information, were also investigated by utilizing univariate and multivariate logistic regressions.Aims
Methods
Degenerative disc disease (DDD) and osteoarthritis (OA) are relatively frequent causes of disability amongst the elderly; they constitute serious socioeconomic costs and significantly impair quality of life. Previous studies to date have found that aggrecan variable number of tandem repeats (VNTR) contributes both to DDD and OA. However, current data are not consistent across studies. The purpose of this study was to evaluate systematically the relationship between aggrecan VNTR, and DDD and/or OA. This study used a highly sensitive search strategy to identify all published studies related to the relationship between aggrecan VNTR and both DDD and OA in multiple databases from January 1996 to December 2016. All identified studies were systematically evaluated using specific inclusion and exclusion criteria. Cochrane methodology was also applied to the results of this study.Objectives
Methods
Many studies have investigated the kinematics of the lumbar spine and the morphological features of the lumbar discs. However, the segment-dependent immediate changes of the lumbar intervertebral space height during flexion-extension motion are still unclear. This study examined the changes of intervertebral space height during flexion-extension motion of lumbar specimens. First, we validated the accuracy and repeatability of a custom-made mechanical loading equipment set-up. Eight lumbar specimens underwent CT scanning in flexion, neural, and extension positions by using the equipment set-up. The changes in the disc height and distance between adjacent two pedicle screw entry points (DASEP) of the posterior approach at different lumbar levels (L3/4, L4/5 and L5/S1) were examined on three-dimensional lumbar models, which were reconstructed from the CT images.Objectives
Methods
Triamcinolone acetonide (TA) is widely used for the treatment of rotator cuff injury because of its anti-inflammatory properties. However, TA can also produce deleterious effects such as tendon degeneration or rupture. These harmful effects could be prevented by the addition of platelet-rich plasma (PRP), however, the anti-inflammatory and anti-degenerative effects of the combined use of TA and PRP have not yet been made clear. The objective of this study was to determine how the combination of TA and PRP might influence the inflammation and degeneration of the rotator cuff by examining rotator cuff-derived cells induced by interleukin (IL)-1ß. Rotator cuff-derived cells were seeded under inflammatory stimulation conditions (with serum-free medium with 1 ng/ml IL-1ß for three hours), and then cultured in different media: serum-free (control group), serum-free + TA (0.1mg/ml) (TA group), serum-free + 10% PRP (PRP group), and serum-free + TA (0.1mg/ml) + 10% PRP (TA+PRP group). Cell morphology, cell viability, and expression of inflammatory and degenerative mediators were assessed.Objectives
Methods
Objectives. Studies which consider the molecular mechanisms of degeneration and regeneration of cartilaginous tissues are seriously hampered by problematic ribonucleic acid (RNA) isolations due to low cell density and the dense, proteoglycan-rich extracellular matrix of cartilage. Proteoglycans tend to co-purify with RNA, they can absorb the full spectrum of UV light and they are potent inhibitors of polymerase chain reaction (PCR). Therefore, the objective of the present study is to compare and optimise different homogenisation methods and RNA isolation kits for an array of cartilaginous tissues. Materials and Methods. Tissue samples such as the nucleus pulposus (NP),
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 intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and
The aim of this study was to examine whether asymmetric loading
influences macrophage elastase (MMP12) expression in different parts
of a rat tail intervertebral disc and growth plate and if MMP12
expression is correlated with the severity of the deformity. A wedge deformity between the ninth and tenth tail vertebrae
was produced with an Ilizarov-type mini external fixator in 45 female
Wistar rats, matched for their age and weight. Three groups were
created according to the degree of deformity (10°, 30° and 50°).
A total of 30 discs and vertebrae were evaluated immunohistochemically
for immunolocalisation of MMP12 expression, and 15 discs were analysed
by western blot and zymography in order to detect pro- and active
MMP12.Objectives
Methods
This short contribution aims to explain how intervertebral disc ‘degeneration’ differs from normal ageing, and to suggest how mechanical loading and constitutional factors interact to cause disc degeneration and prolapse. We suggest that disagreement on these matters in medico-legal practice often arises from a misunderstanding of the nature of ‘soft-tissue injuries’.
The belief that an intervertebral disc must degenerate
before it can herniate has clinical and medicolegal significance,
but lacks scientific validity. We hypothesised that tissue changes
in herniated discs differ from those in discs that degenerate without
herniation. Tissues were obtained at surgery from 21 herniated discs
and 11 non-herniated discs of similar degeneration as assessed by
the Pfirrmann grade. Thin sections were graded histologically, and
certain features were quantified using immunofluorescence combined
with confocal microscopy and image analysis. Herniated and degenerated
tissues were compared separately for each tissue type: nucleus, inner
annulus and outer annulus. Herniated tissues showed significantly greater proteoglycan loss
(outer annulus), neovascularisation (annulus), innervation (annulus),
cellularity/inflammation (annulus) and expression of matrix-degrading
enzymes (inner annulus) than degenerated discs. No significant differences
were seen in the nucleus tissue from herniated and degenerated discs.
Degenerative changes start in the nucleus, so it seems unlikely
that advanced degeneration caused herniation in 21 of these 32 discs.
On the contrary, specific changes in the annulus can be interpreted
as the consequences of herniation, when disruption allows local
swelling, proteoglycan loss, and the ingrowth of blood vessels,
nerves and inflammatory cells. In conclusion, it should not be assumed that degenerative changes
always precede disc herniation. Cite this article:
No previous studies have examined the physical
characteristics of patients with cauda equina syndrome (CES). We compared
the anthropometric features of patients who developed CES after
a disc prolapse with those who did not but who had symptoms that
required elective surgery. We recorded the age, gender, height,
weight and body mass index (BMI) of 92 consecutive patients who
underwent elective lumbar discectomy and 40 consecutive patients who
underwent discectomy for CES. On univariate analysis, the mean BMI
of the elective discectomy cohort (26.5 kg/m2 (16.6 to
41.7) was very similar to that of the age-matched national mean
(27.6 kg/m2, p = 1.0). However, the mean BMI of the CES
cohort (31.1 kg/m2 (21.0 to 54.9)) was significantly
higher than both that of the elective group (p <
0.001) and the
age-matched national mean (p <
0.001). A similar pattern was
seen with the weight of the groups. Multivariate logistic regression
analysis was performed, adjusted for age, gender, height, weight
and BMI. Increasing BMI and weight were strongly associated with
an increased risk of CES (odds ratio (OR) 1.17, p <
0.001; and
OR 1.06, p <
0.001, respectively). However, increasing height
was linked with a reduced risk of CES (OR 0.9, p <
0.01). The
odds of developing CES were 3.7 times higher (95% confidence interval
(CI) 1.2 to 7.8, p = 0.016) in the overweight and obese (as defined
by the World Health Organization: BMI ≥ 25 kg/m2) than
in those of ideal weight. Those with very large discs (obstructing
>
75% of the spinal canal) had a larger BMI than those with small
discs (obstructing <
25% of the canal; p <
0.01). We therefore
conclude that increasing BMI is associated with CES.
