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Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism. Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1β; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67phox was involved in suramin-enhanced chondrocyte phenotype maintenance.Aims
Methods
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
To systematically evaluate whether bracing can effectively achieve curve regression in patients with adolescent idiopathic scoliosis (AIS), and to identify any predictors of curve regression after bracing. Two independent reviewers performed a comprehensive literature search in PubMed, Ovid, Web of Science, Scopus, and Cochrane Library to obtain all published information about the effectiveness of bracing in achieving curve regression in AIS patients. Search terms included “brace treatment” or “bracing,” “idiopathic scoliosis,” and “curve regression” or “curve reduction.” Inclusion criteria were studies recruiting patients with AIS undergoing brace treatment and one of the study outcomes must be curve regression or reduction, defined as > 5° reduction in coronal Cobb angle of a major curve upon bracing completion. Exclusion criteria were studies including non-AIS patients, studies not reporting p-value or confidence interval, animal studies, case reports, case series, and systematic reviews. The GRADE approach to assessing quality of evidence was used to evaluate each publication.Aims
Methods
The aim of this study was to investigate whether the type of cervical disc herniation influences the severity of symptoms at the time of presentation, and the outcome after surgical treatment. The type and extent of disc herniation at the time of presentation in 108 patients who underwent anterior discectomy for cervical radiculopathy were analyzed on MRI, using a four-point scale. These were dichotomized into disc bulge and disc herniation groups. Clinical outcomes were evaluated using the Neck Disability Index (NDI), 36-Item Short Form Survey (SF-36), and a visual analogue scale (VAS) for pain in the neck and arm at baseline and two years postoperatively. The perceived recovery was also assessed at this time.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
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
Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with limited coding potential, which have emerged as novel regulators in many biological and pathological processes, including growth, development, and oncogenesis. Accumulating evidence suggests that lncRNAs have a special role in the osteogenic differentiation of various types of cell, including stem cells from different sources such as embryo, bone marrow, adipose tissue and periodontal ligaments, and induced pluripotent stem cells. Involved in complex mechanisms, lncRNAs regulate osteogenic markers and key regulators and pathways in osteogenic differentiation. In this review, we provide insights into the functions and molecular mechanisms of lncRNAs in osteogenesis and highlight their emerging roles and clinical value in regenerative medicine and osteogenesis-related diseases.
Although success has been achieved with implantation of bone marrow mesenchymal stem cells (bMSCs) in degenerative discs, its full potential may not be achieved if the harsh environment of the degenerative disc remains. Axial distraction has been shown to increase hydration and nutrition. Combining both therapies may have a synergistic effect in reversing degenerative disc disease. In order to evaluate the effect of bMSC implantation, axial distraction and combination therapy in stimulating regeneration and retarding degeneration in degenerative discs, we first induced disc degeneration by axial loading in a rabbit model. The rabbits in the intervention groups performed better with respect to disc height, morphological grading, histological scoring and average dead cell count. The groups with distraction performed better than those without on all criteria except the average dead cell count. Our findings suggest that bMSC implantation and distraction stimulate regenerative changes in degenerative discs in a rabbit model.
The June 2012 Research Roundup360 looks at: platelet-rich plasma; ageing, bone and mesenchymal stem cells; cytokines and the herniated intervertebral disc; ulcerative colitis, Crohn’s disease and anti-inflammatories; the effect of NSAIDs on bone healing; osteoporosis of the fractured hip; herbal medicine and recovery after acute muscle injury; and ultrasound and the time to fracture union.
The widespread use of MRI has revolutionised
the diagnostic process for spinal disorders. A typical protocol
for spinal MRI includes T1 and T2 weighted sequences in both axial
and sagittal planes. While such an imaging protocol is appropriate
to detect pathological processes in the vast majority of patients,
a number of additional sequences and advanced techniques are emerging.
The purpose of the article is to discuss both established techniques
that are gaining popularity in the field of spinal imaging and to
introduce some of the more novel ‘advanced’ MRI sequences with examples
to highlight their potential uses. Cite this article:
The pathophysiology of intervertebral disc degeneration has been extensively studied. Various factors have been suggested as influencing its aetiology, including mechanical factors, such as compressive loading, shear stress and vibration, as well as ageing, genetic, systemic and toxic factors, which can lead to degeneration of the disc through biochemical reactions. How are these factors linked? What is their individual importance? There is no clear evidence indicating whether ageing in the presence of repetitive injury or repetitive injury in the absence of ageing plays a greater role in the degenerative process. Mechanical factors can trigger biochemical reactions which, in turn, may promote the normal biological changes of ageing, which can also be accelerated by genetic factors. Degradation of the molecular structure of the disc during ageing renders it more susceptible to superimposed mechanical injuries. This review supports the theory that degeneration of the disc has a complex multifactorial aetiology. Which factors initiate the events in the degenerative cascade is a question that remains unanswered, but most evidence points to an age-related process influenced primarily by mechanical and genetic factors.
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’.
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
We report on two cases of infective spondylodiscitis
caused by We describe the clinical features, investigations and treatment
options.
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:
The August 2015 Spine Roundup360 looks at: Steroids may be useful in avoiding dysphagia in anterior cervical discectomy and fusion (ACDF); Perhaps X-Stop ought to stop?; Is cervical plexus block in ACDF the gateway to day case spinal surgery?; Epidural past its heyday?; Steroids in lumbar back pain; Lumbar disc replacement improving; Post-discectomy arthritis
Lumbar disc herniation (LDH) is uncommon in youth
and few cases are treated surgically. Very few outcome studies exist
for LDH surgery in this age group. Our aim was to explore differences
in gender in pre-operative level of disability and outcome of surgery
for LDH in patients aged ≤ 20 years using prospectively collected
data. From the national Swedish SweSpine register we identified 180
patients with one-year and 108 with two-year follow-up data ≤ 20
years of age, who between the years 2000 and 2010 had a primary
operation for LDH. Both male and female patients reported pronounced impairment
before the operation in all patient reported outcome measures, with
female patients experiencing significantly greater back pain, having
greater analgesic requirements and reporting significantly inferior
scores in EuroQol (EQ-5D-index), EQ-visual analogue scale, most aspects
of Short Form-36 and Oswestry Disabilities Index, when compared
with male patients. Surgery conferred a statistically significant
improvement in all registered parameters, with few gender discrepancies.
Quality of life at one year following surgery normalised in both
males and females and only eight patients (4.5%) were dissatisfied with
the outcome. Virtually all parameters were stable between the one-
and two-year follow-up examination. LDH surgery leads to normal health and a favourable outcome in
both male and female patients aged 20 years or younger, who failed
to recover after non-operative management. 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.
Modern principles for the treatment of open fractures include stabilisation of the bone and management of the soft tissues. Wound debridement and irrigation is thought to be the mainstay in reducing the incidence of infection. Although numerous studies on animals and humans have focused on the type of irrigation performed, little is known of the factors which influence irrigation. This paper evaluates the evidence, particularly with regard to additives and the mode of delivery of irrigation fluid. Normal saline should be used and although many antiseptics and antibiotics have been employed, no consensus has been reached as to the ideal additive. Despite the advocates of high-pressure methods highlighting the improved dilutional ability of such techniques, the results are inconclusive and these irrigation systems are not without complications. New systems for debridement are currently being investigated, and an ideal method has yet to be determined.