Aims. 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. Methods. 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. Results. TWAS identified 295 genes with permutation p-values < 0.05 for skeletal muscle and 79 genes associated for the whole blood, such as RCHY1 (PTWAS = 0.001). Those genes were enriched in 112 gene ontology (GO) terms and five Kyoto Encyclopedia of Genes and Genomes pathways, such as ‘chemical carcinogenesis - reactive oxygen species’ (LogP value = −2.139). Further comparing the TWAS significant genes with the differentially expressed genes identified by mRNA expression profiles of LSS found 18 overlapped genes, such as
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 annulus fibrosus (AF) cells and in the human nucleus pulposus (NP) immortalized cell line HNPSV-1. We determined messenger RNA (mRNA) and protein levels of relevant factors involved in inflammatory responses, by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. We also studied the presence of mCRP in human AF and NP tissues by immunohistochemistry. Results. We demonstrated that mCRP increases nitric oxide synthase 2 (NOS2), cyclooxygenase 2 (COX2), matrix metalloproteinase 13 (MMP13), vascular cell adhesion molecule 1 (VCAM1),
Aims. This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect. Methods. 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. Results. Western blot analysis confirmed the expression of cleaved CASP-1 and melatonin receptor (MT-1A-R) in NPCs. The cultured NPCs were identified by detecting the expression of CD24, collagen type II, and aggrecan. After treatment with hydrogen peroxide, the pyroptosis-related proteins NLR family pyrin domain containing 3 (NLRP3), cleaved CASP-1, N-terminal fragment of gasdermin D (GSDMD-N),
To investigate the correlations among cytokines and regulatory T cells (T-regs) in ankylosing spondylitis (AS) patients, and their changes after anti-tumour necrosis factor-α (TNF-α) treatment. We included 72 AS patients with detailed medical records, disease activity score (Bath Ankylosing Spondylitis Disease Activity Index), functional index (Bath Ankylosing Spondylitis Functional Index), and laboratory data (interleukin (IL)-2, IL-4, IL-10, TNF-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, ESR, and CRP). Their peripheral blood mononuclear cells (PBMCs) were marked with anti-CD4, anti-CD25, and anti-FoxP3 antibodies, and triple positive T cells were gated by flow cytometry as T-regs. Their correlations were calculated and the changes after anti-TNF-α therapy were compared.Aims
Methods
Inflammatory response plays a pivotal role in the pathophysiological process of intervertebral disc degeneration (IDD). A20 (also known as tumour necrosis factor alpha-induced protein 3 (TNFAIP3)) is a ubiquitin-editing enzyme that restricts nuclear factor-kappa B (NF-κB) signalling. A20 prevents the occurrence of multiple inflammatory diseases. However, the role of A20 in the initiation of IDD has not been elucidated. The aim of the study was to investigate the effect of A20 in senescence of TNF alpha (TNF-α)-induced nucleus pulposus cells (NPCs). Immunohistochemical staining was performed to observe the expression of A20 in normal and degenerated human intervertebral discs. The NPCs were dissected from the tail vertebrae of healthy male Sprague-Dawley rats and were cultured in the incubator. In the experiment, TNF-α was used to mimic the inflammatory environment of IDD. The cell viability and senescence were examined to investigate the effect of A20 on TNF-α-treated NPCs. The expression of messenger RNA (mRNA)-encoding proteins related to matrix macromolecules (collagen II, aggrecan) and senescence markers (p53, p16). Additionally, NF-κB/p65 activity of NPCs was detected within different test compounds.Aims
Methods
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.
This article reviews the current knowledge of
the intervertebral disc (IVD) and its association with low back
pain (LBP). The normal IVD is a largely avascular and aneural structure
with a high water content, its nutrients mainly diffusing through
the end plates. IVD degeneration occurs when its cells die or become
dysfunctional, notably in an acidic environment. In the process
of degeneration, the IVD becomes dehydrated and vascularised, and
there is an ingrowth of nerves. Although not universally the case,
the altered physiology of the IVD is believed to precede or be associated
with many clinical symptoms or conditions including low back and/or
lower limb pain, paraesthesia, spinal stenosis and disc herniation. New treatment options have been developed in recent years. These
include biological therapies and novel surgical techniques (such
as total disc replacement), although many of these are still in
their experimental phase. Central to developing further methods
of treatment is the need for effective ways in which to assess patients
and measure their outcomes. However, significant difficulties remain
and it is therefore an appropriate time to be further investigating
the scientific basis of and treatment of LBP.
Low bone mass and osteopenia have been described in the axial and peripheral skeleton of patients with adolescent idiopathic scoliosis (AIS). Recently, many studies have shown that gene polymorphism is related to osteoporosis. However, no studies have linked the association between IL6 gene polymorphism and bone mass in AIS. This study examined the association between bone mass and IL6 gene polymorphism in 198 girls with AIS. The polymorphisms of IL6-597 G→A, IL6-572 G→C and IL6-174 G→A and the bone mineral density in the lumbar spine and femoral neck were analysed and compared with their levels in healthy controls. The mean bone mineral density at both sites in patients with AIS was decreased compared with controls (p = 0.0022 and p = 0.0013, respectively). Comparison of genotype frequencies between AIS and healthy controls revealed a statistically significant difference in IL6-572 G→C polymorphism (p = 0.0305). There was a significant association between the IL6-572 G→C polymorphism and bone mineral density in the lumbar spine, with the CC genotype significantly higher with the GC (p = 0.0124) or GG (p = 0.0066) genotypes. These results suggest that the IL6-572 G→C polymorphism is associated with bone mineral density in the lumbar spine in Korean girls with AIS.
The post-operative changes in the serum levels of CRP and serum amyloid A (SAA) were investigated prospectively in 106 patients after posterior lumbar interbody fusion. In 96 patients who did not have complications related to infection within the first year after operation, the median levels of CRP before operation and on days 3, 7 and 13 after were 0.02 (0.01 to 0.03), 9.12 (2.36 to 19.82), 1.64 (0.19 to 6.10) and 0.53 (0.05 to 2.94) mg/dl, respectively and for SAA, 2.6 (2.0 to 3.8), 1312.1 (58.0 to 3579.8), 77.3 (1.8 to 478.4), 14.1 (0.5 to 71.9) μg/ml, respectively. The levels on day 3 were the highest for both CRP and SAA and significantly decreased (p <
0.01) by day 7 and day 13. In regard to CRP, no patient had less than the reference level (0.1 mg/dl) on day 7. In only three had the level decreased to the reference level, while in 93 it was above this on day 13. However, for SAA, the levels became normal on day 7 in 10 cases and on day 13 in 34 cases. The ratios relative to the levels on day 3 were significantly lower for SAA compared with CRP on day 7 and day 13. Of the ten patients with infection in the early stages, the level of CRP decreased slightly but an increase in SAA was observed in six. We concluded that SAA is better than CRP as a post-operative inflammatory marker.
Discogenic low back pain is a common cause of disability, but its pathogenesis is poorly understood. We collected 19 specimens of lumbar intervertebral discs from 17 patients with discogenic low back pain during posterior lumbar interbody fusion, 12 from physiologically ageing discs and ten from normal control discs. We investigated the histological features and assessed the immunoreactive activity of neurofilament (NF200) and neuropeptides such as substance P (SP) and vasoactive-intestinal peptide (VIP) in the nerve fibres. The distinct histological characteristic of the painful disc was the formation of a zone of vascularised granulation tissue from the nucleus pulposus to the outer part of the annulus fibrosus along the edges of the fissures. SP-, NF- and VIP-immunoreactive nerve fibres in the painful discs were more extensive than in the control discs. Growth of nerves deep into the annulus fibrosus and nucleus pulposus was observed mainly along the zone of granulation tissue in the painful discs. This suggests that the zone of granulation tissue with extensive innervation along the tears in the posterior part of the painful disc may be responsible for causing the pain of discography and of discogenic low back pain.
