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Bone & Joint Research
Vol. 12, Issue 2 | Pages 133 - 137
10 Feb 2023
Liao H Tsai C

Aims. 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. Methods. 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. Results. The frequency of T-regs in PBMCs was positively correlated to ESR and CRP in AS (r = 0.35 and 0.43; p = 0.032 and 0.027, respectively), and there was also a significant correlation between serum level of TNF-α and CRP (p = 0.041). The frequency of T-regs in PBMCs positively correlated to serum levels of TNF-α, IL-10, and TGF-β, while IL-2, IL-4, and IFN-γ showed opposite results. After anti-TNF-α treatment, there were significantly lower serum levels of TNF-α, IL-10, TGF-β, and frequency of T-regs in PBMCs among these AS patients (p = 0.026, 0.032, 0.029, and 0.037, respectively). Conclusion. In AS patients, proinflammatory cytokine may give positive feedback to induce more T-reg production and anti-inflammatory cytokine secretion to suppress this inflammatory status, and they can be reversed by anti-TNF-α therapy. However, the detailed interactions among T-regs and complex cytokine networks in autoinflammatory diseases still need more studies and further functional assay. Cite this article: Bone Joint Res 2023;12(2):133–137


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.


Bone & Joint Research
Vol. 12, Issue 9 | Pages 522 - 535
4 Sep 2023
Zhang G Li L Luo Z Zhang C Wang Y Kang X

Aims

This study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).

Methods

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.


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.


The Bone & Joint Journal
Vol. 102-B, Issue 5 | Pages 627 - 631
1 May 2020
Mahon J Ahern DP Evans SR McDonnell J Butler JS

Aims

The timing of surgical fixation in spinal fractures is a contentious topic. Existing literature suggests that early stabilization leads to reduced morbidity, improved neurological outcomes, and shorter hospital stay. However, the quality of evidence is low and equivocal with regard to the safety of early fixation in the severely injured patient. This paper compares complication profiles between spinal fractures treated with early fixation and those treated with late fixation.

Methods

All patients transferred to a national tertiary spinal referral centre for primary surgical fixation of unstable spinal injuries without preoperative neurological deficit between 1 July 2016 and 20 October 2017 were eligible for inclusion. Data were collected retrospectively. Patients were divided into early and late cohorts based on timing from initial trauma to first spinal operation. Early fixation was defined as within 72 hours, and late fixation beyond 72 hours.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 1 | Pages 66 - 71
1 Jan 2007
Suh KT Lee SS Kim SJ Kim YK Lee JS

The scoliosis observed in chickens after pinealectomy resembles that seen in humans with an adolescent idiopathic scoliosis, suggesting that melatonin deficiency may be responsible. However, to date there have been no studies of pineal gland glucose metabolism in patients with adolescent idiopathic scoliosis that might support this hypothesis.

We examined the excretion of urinary 6-sulfatoxyl-melatonin as well as the glucose metabolism of the pineal gland in 14 patients with an adolescent idiopathic scoliosis and compared them with those of 13 gender-matched healthy controls using F-18 fluorodeoxyglucose brain positron emission tomography. There was no significant difference in the level of urinary 6-sulfatoxyl-melatonin or pineal gland metabolism between the study and the control group. We conclude that permanent melatonin deficiency is not a causative factor in the aetiology of adolescent idiopathic scoliosis.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 10 | Pages 1393 - 1398
1 Oct 2012
Mattila M Jalanko T Puisto V Pajulo O Helenius IJ

We compared the clinical, radiological and quality-of-life outcomes between hybrid and total pedicle screw instrumentation in patients undergoing surgery for neuromuscular scoliosis. A matched comparison using prospectively collected data was undertaken. A total of 66 patients underwent posterior or anteroposterior correction and fusion with hybrid (n = 33, mean age at surgery 15.8 years (9.10 to 19.6)) or total pedicle screw instrumentation (n = 33, mean age 14.7 years (7.0 to 20.7)) with a minimum follow-up of two years. The major curve pre-operatively was a mean of 87° (sd 29, 25° to 141°) and 81° (sd 18, 47° to 116°) in the hybrid and total pedicle screw groups, respectively (p = 0.29) and at a minimum of two years it was 33° (sd 20; 2° to 87°) and 20° (sd 12; 1° to 55°), respectively (p = 0.0016). The mean correction of the major curve was 59% (41% to 88%) in the hybrid and 75% (43% to 99%) in the total pedicle screw groups at two-year follow-up (p = 0.0011). The mean operating time was 7.45 hours (sd 2.18) and 6.04 hours (sd 1.71) in the hybrid and total pedicle screw groups, respectively (p = 0.001), and the mean intra-operative blood loss was 3760 ml (sd 2790) and 1785 ml (sd 1110), respectively (p = 0.001).

Total pedicle screw instrumentation provided shorter operating times, less blood loss and better correction of the major curve compared with hybrid constructs in patients undergoing surgery for neuromuscular scoliosis.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 8 | Pages 1118 - 1122
1 Aug 2010
Lee JS Suh KT Eun IS

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.