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Bone & Joint Research
Vol. 2, Issue 8 | Pages 169 - 178
1 Aug 2013
Rodrigues-Pinto R Richardson SM Hoyland JA

Mesenchymal stem-cell based therapies have been proposed as novel treatments for intervertebral disc degeneration, a prevalent and disabling condition associated with back pain. The development of these treatment strategies, however, has been hindered by the incomplete understanding of the human nucleus pulposus phenotype and by an inaccurate interpretation and translation of animal to human research. This review summarises recent work characterising the nucleus pulposus phenotype in different animal models and in humans and integrates their findings with the anatomical and physiological differences between these species. Understanding this phenotype is paramount to guarantee that implanted cells restore the native functions of the intervertebral disc. Cite this article: Bone Joint Res 2013;2:169–78


Bone & Joint Research
Vol. 12, Issue 6 | Pages 387 - 396
26 Jun 2023
Xu J Si H Zeng Y Wu Y Zhang S Shen B

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.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 80 - 90
20 Jan 2023
Xu J Si H Zeng Y Wu Y Zhang S Liu Y Li M Shen B

Aims

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.

Methods

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.


The Bone & Joint Journal
Vol. 106-B, Issue 11 | Pages 1333 - 1341
1 Nov 2024
Cheung PWH Leung JHM Lee VWY Cheung JPY

Aims

Developmental cervical spinal stenosis (DcSS) is a well-known predisposing factor for degenerative cervical myelopathy (DCM) but there is a lack of consensus on its definition. This study aims to define DcSS based on MRI, and its multilevel characteristics, to assess the prevalence of DcSS in the general population, and to evaluate the presence of DcSS in the prediction of developing DCM.

Methods

This cross-sectional study analyzed MRI spine morphological parameters at C3 to C7 (including anteroposterior (AP) diameter of spinal canal, spinal cord, and vertebral body) from DCM patients (n = 95) and individuals recruited from the general population (n = 2,019). Level-specific median AP spinal canal diameter from DCM patients was used to screen for stenotic levels in the population-based cohort. An individual with multilevel (≥ 3 vertebral levels) AP canal diameter smaller than the DCM median values was considered as having DcSS. The most optimal cut-off canal diameter per level for DcSS was determined by receiver operating characteristic analyses, and multivariable logistic regression was performed for the prediction of developing DCM that required surgery.


The Bone & Joint Journal
Vol. 104-B, Issue 5 | Pages 627 - 632
2 May 2022
Sigmundsson FG Joelson A Strömqvist F

Aims

Lumbar disc prolapse is a frequent indication for surgery. The few available long-term follow-up studies focus mainly on repeated surgery for recurrent disease. The aim of this study was to analyze all reasons for additional surgery for patients operated on for a primary lumbar disc prolapse.

Methods

We retrieved data from the Swedish spine register about 3,291 patients who underwent primary surgery for a lumbar disc prolapse between January 2007 and December 2008. These patients were followed until December 2020 to record all additional lumbar spine operations and the reason for them.


Bone & Joint Research
Vol. 10, Issue 5 | Pages 328 - 339
31 May 2021
Jia X Huang G Wang S Long M Tang X Feng D Zhou Q

Aims

Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

Methods

In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI.


Bone & Joint Research
Vol. 9, Issue 5 | Pages 225 - 235
1 May 2020
Peng X Zhang C Bao J Zhu L Shi R Xie Z Wang F Wang K Wu X

Aims

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).

Methods

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.


The Bone & Joint Journal
Vol. 101-B, Issue 2 | Pages 154 - 161
1 Feb 2019
Cheung PWH Fong HK Wong CS Cheung JPY

Aims

The aim of this study was to determine the influence of developmental spinal stenosis (DSS) on the risk of re-operation at an adjacent level.

Patients and Methods

This was a retrospective study of 235 consecutive patients who had undergone decompression-only surgery for lumbar spinal stenosis and had a minimum five-year follow-up. There were 106 female patients (45.1%) and 129 male patients (54.9%), with a mean age at surgery of 66.8 years (sd 11.3). We excluded those with adult deformity and spondylolisthesis. Presenting symptoms, levels operated on initially and at re-operation were studied. MRI measurements included the anteroposterior diameter of the bony spinal canal, the degree of disc degeneration, and the thickness of the ligamentum flavum. DSS was defined by comparative measurements of the bony spinal canal. Risk factors for re-operation at the adjacent level were determined and included in a multivariate stepwise logistic regression for prediction modelling. Odds ratios (ORs) with 95% confidence intervals were calculated.


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 9 | Pages 1237 - 1247
1 Sep 2005
Mehta MH

This prospective study of 136 children with progressive infantile scoliosis treated under the age of four years, and followed up for nine years, shows that the scoliosis can be reversed by harnessing the vigorous growth of the infant to early treatment by serial corrective plaster jackets.

In 94 children (group 1), who were referred and treated in the early stages of progression, at a mean age of one year seven months (6 to 48 months) and with a mean Cobb angle of 32° (11° to 65°), the scoliosis resolved by a mean age of three years and six months. They needed no further treatment and went on to lead a normal life. At the last follow-up, their mean age was 11 years and two months (1 year 10 months to 25 years 2 months), 23 (24.5%) were at Risser stages 4 and 5 and 13 girls were post-menarchal.

In 42 children (group 2), who were referred late at a mean age of two years and six months (11 to 48 months) and with a mean Cobb angle of 52° (23° to 92°), treatment could only reduce but not reverse the deformity. At the last follow-up, at a mean age of ten years and four months (1 year 9 months to 22 years 1 month), eight children (19%) were at Risser stages 4 and 5 and five girls were post-menarchal. Fifteen children (35.7%) had undergone spinal fusion, as may all the rest eventually.


Bone & Joint 360
Vol. 3, Issue 2 | Pages 32 - 65
1 Apr 2014
Adams MA

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 Bone & Joint Journal
Vol. 96-B, Issue 1 | Pages 100 - 105
1 Jan 2014
Shapiro F Zurakowski D Bui T Darras BT

We determined the frequency, rate and extent of development of scoliosis (coronal plane deformity) in wheelchair-dependent patients with Duchenne muscular dystrophy (DMD) who were not receiving steroid treatment. We also assessed kyphosis and lordosis (sagittal plane deformity). The extent of scoliosis was assessed on sitting anteroposterior (AP) spinal radiographs in 88 consecutive non-ambulatory patients with DMD. Radiographs were studied from the time the patients became wheelchair-dependent until the time of spinal fusion, or the latest assessment if surgery was not undertaken. Progression was estimated using a longitudinal mixed-model regression analysis to handle repeated measurements.

Scoliosis ≥ 10° occurred in 85 of 88 patients (97%), ≥ 20° in 78 of 88 (89%) and ≥ 30° in 66 of 88 patients (75%). The fitted longitudinal model revealed that time in a wheelchair was a highly significant predictor of the magnitude of the curve, independent of the age of the patient (p <  0.001). Scoliosis developed in virtually all DMD patients not receiving steroids once they became wheelchair-dependent, and the degree of deformity deteriorated over time.

In general, scoliosis increased at a constant rate, beginning at the time of wheelchair-dependency (p < 0.001). In some there was no scoliosis for as long as three years after dependency, but scoliosis then developed and increased at a constant rate. Some patients showed a rapid increase in the rate of progression of the curve after a few years – the clinical phenomenon of a rapidly collapsing curve over a few months.

A sagittal plane kyphotic deformity was seen in 37 of 60 patients (62%) with appropriate radiographs, with 23 (38%) showing lumbar lordosis (16 (27%) abnormal and seven (11%) normal).

This study provides a baseline to assess the effects of steroids and other forms of treatment on the natural history of scoliosis in patients with DMD, and an approach to assessing spinal deformity in the coronal and sagittal planes in wheelchair-dependent patients with other neuromuscular disorders.

Cite this article: Bone Joint J 2014;96-B:100–5.