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Bone & Joint Research
Vol. 7, Issue 7 | Pages 494 - 500
1 Jul 2018
Jiang L Zhu X Rong J Xing B Wang S Liu A Chu M Huang G

Objectives. Given the function of adiponectin (ADIPOQ) on the inflammatory condition of obesity and osteoarthritis (OA), we hypothesized that the ADIPOQ gene might be a candidate gene for a marker of susceptibility to OA. Methods. We systematically screened three tagging polymorphisms (rs182052, rs2082940 and rs6773957) in the ADIPOQ gene, and evaluated the association between the genetic variants and OA risk in a case-controlled study that included 196 OA patients and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Results. The single nucleotide polymorphism (SNP) rs182052 was found to be potentially associated with knee OA risk (additive model: odds ratio = 1.38; 95% confidence interval 1.07 to 1.76; p = 0.012). Furthermore, a non-significant association was observed for rs182052 and body mass index with regard to OA risk in interaction analyses (p = 0.063). Similarly, no significant interaction was detected for rs182052 and age with regard to OA risk (p = 0.614). Conclusion. These findings suggest that the SNP rs182052 in the ADIPOQ gene may potentially modify individual susceptibility to knee OA in the Chinese population. Further studies are warranted to investigate our findings in more depth. Cite this article: L. Jiang, X. Zhu, J. Rong, B. Xing, S. Wang, A. Liu, M. Chu, G. Huang. Obesity, osteoarthritis and genetic risk: The rs182052 polymorphism in the ADIPOQ gene is potentially associated with risk of knee osteoarthritis. Bone Joint Res 2018;7:494–500. DOI: 10.1302/2046-3758.77.BJR-2017-0274.R1


Bone & Joint Research
Vol. 6, Issue 10 | Pages 572 - 576
1 Oct 2017
Wang W Huang S Hou W Liu Y Fan Q He A Wen Y Hao J Guo X Zhang F

Objectives. Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data. Method. We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients’ BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05. Results. We identified multiple gene sets associated with BMD in one or more regions, including relevant known biological gene sets such as the Reactome Circadian Clock (GSEA p-value = 1.0 × 10. -4. for LS and 2.7 × 10. -2. for femoral necks BMD in eQTLs-based GSEA) and insulin-like growth factor receptor binding (GSEA p-value = 5.0 × 10. -4. for femoral necks and 2.6 × 10. -2. for lumbar spines BMD in meQTLs-based GSEA). Conclusion. Our results provided novel clues for subsequent functional analysis of bone metabolism, and illustrated the benefit of integrating eQTLs and meQTLs data into pathway association analysis for genetic studies of complex human diseases. Cite this article: W. Wang, S. Huang, W. Hou, Y. Liu, Q. Fan, A. He, Y. Wen, J. Hao, X. Guo, F. Zhang. Integrative analysis of GWAS, eQTLs and meQTLs data suggests that multiple gene sets are associated with bone mineral density. Bone Joint Res 2017;6:572–576


Bone & Joint Research
Vol. 6, Issue 7 | Pages 439 - 445
1 Jul 2017
Sekimoto T Ishii M Emi M Kurogi S Funamoto T Yonezawa Y Tajima T Sakamoto T Hamada H Chosa E

Objectives

We have previously investigated an association between the genome copy number variation (CNV) and acetabular dysplasia (AD). Hip osteoarthritis is associated with a genetic polymorphism in the aspartic acid repeat in the N-terminal region of the asporin (ASPN) gene; therefore, the present study aimed to investigate whether the CNV of ASPN is involved in the pathogenesis of AD.

Methods

Acetabular coverage of all subjects was evaluated using radiological findings (Sharp angle, centre-edge (CE) angle, acetabular roof obliquity (ARO) angle, and minimum joint space width). Genomic DNA was extracted from peripheral blood leukocytes. Agilent’s region-targeted high-density oligonucleotide tiling microarray was used to analyse 64 female AD patients and 32 female control subjects. All statistical analyses were performed using EZR software (Fisher’s exact probability test, Pearson’s correlation test, and Student’s t-test).


Objectives

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.

Methods

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.


Bone & Joint Research
Vol. 6, Issue 3 | Pages 132 - 136
1 Mar 2017
Yuenyongviwat V Ingviya N Pathaburee P Tangtrakulwanich B

Objectives

Vancomycin and fosfomycin are antibiotics commonly used to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. This study compares the in vitro inhibitory effects against MRSA of articulating cement spacers impregnated with either vancomycin or fosfomycin.

Methods

Vancomycin-impregnated articulating cement spacers and fosfomycin-impregnated articulating cement spacers were immersed in sterile phosphate-buffered saline (PBS) solutions and then incubated. Samples were collected for bioactivity evaluation. The aliquots were tested for MRSA inhibition with the disc diffusion method, and the inhibition zone diameters were measured. The inhibition zone differences were evaluated using the Wilcoxon Rank Sum Test.


Bone & Joint Research
Vol. 7, Issue 5 | Pages 362 - 372
1 May 2018
Ueda Y Inui A Mifune Y Sakata R Muto T Harada Y Takase F Kataoka T Kokubu T Kuroda R

Objectives

The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy.

Methods

Using tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours in vitro. In an in vivo study, using diabetic rats and controls, NOX1 and 4 expressions in Achilles tendon were also determined.


Bone & Joint Research
Vol. 6, Issue 5 | Pages 296 - 306
1 May 2017
Samara E Moriarty TF Decosterd LA Richards RG Gautier E Wahl P

Objectives

Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature.

Methods

In this study, a total of 38 frequently used antibiotic agents were maintained at 37°C in saline solution, and degradation and antibacterial activity assessed over six weeks. The impact of an initial supplementary heat exposure mimicking exothermically curing bone cement was also tested as this material is commonly used as a local delivery vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity over time was determined by the Kirby-Bauer disk diffusion assay.


Bone & Joint Research
Vol. 5, Issue 12 | Pages 594 - 601
1 Dec 2016
Li JJ Wang BQ Fei Q Yang Y Li D

Objectives

In order to screen the altered gene expression profile in peripheral blood mononuclear cells of patients with osteoporosis, we performed an integrated analysis of the online microarray studies of osteoporosis.

Methods

We searched the Gene Expression Omnibus (GEO) database for microarray studies of peripheral blood mononuclear cells in patients with osteoporosis. Subsequently, we integrated gene expression data sets from multiple microarray studies to obtain differentially expressed genes (DEGs) between patients with osteoporosis and normal controls. Gene function analysis was performed to uncover the functions of identified DEGs.


Bone & Joint Research
Vol. 6, Issue 1 | Pages 57 - 65
1 Jan 2017
Gumucio JP Flood MD Bedi A Kramer HF Russell AJ Mendias CL

Objectives

Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics.

Methods

Chronic supraspinatus tears were induced in adult rats, and repaired 28 days later. Rats received 0 mg/kg, 3 mg/kg, or 10 mg/kg GSK1120360A daily. Collagen content, contractility, fibre type distribution and size, the expression of genes involved in fibrosis, lipid accumulation, atrophy and inflammation, and the mechanical properties of the enthesis were then assessed two weeks following surgical repair.


Bone & Joint Research
Vol. 5, Issue 7 | Pages 314 - 319
1 Jul 2016
Xiao X Hao J Wen Y Wang W Guo X Zhang F

Objectives

The molecular mechanism of rheumatoid arthritis (RA) remains elusive. We conducted a protein-protein interaction network-based integrative analysis of genome-wide association studies (GWAS) and gene expression profiles of RA.

Methods

We first performed a dense search of RA-associated gene modules by integrating a large GWAS meta-analysis dataset (containing 5539 RA patients and 20 169 healthy controls), protein interaction network and gene expression profiles of RA synovium and peripheral blood mononuclear cells (PBMCs). Gene ontology (GO) enrichment analysis was conducted by DAVID. The protein association networks of gene modules were generated by STRING.


Bone & Joint Research
Vol. 4, Issue 4 | Pages 50 - 55
1 Apr 2015
Sekimoto T Kurogi S Funamoto T Ota T Watanabe S Sakamoto T Hamada H Chosa E

Objectives

Excessive acetabular coverage is the most common cause of pincer-type femoroacetabular impingement. To date, an association between acetabular over-coverage and genetic variations has not been studied. In this study we investigated the association between single nucleotide polymorphisms (SNPs) of paralogous Homeobox (HOX)9 genes and acetabular coverage in Japanese individuals to identify a possible genetic variation associated with acetabular over-coverage.

Methods

We investigated 19 total SNPs in the four HOX9 paralogs, then focused in detail on seven of those located in the 3’ untranslated region of HOXB9 (rs8844, rs3826541, rs3826540, rs7405887, rs2303485, rs2303486, rs79931349) using a case-control association study. The seven HOXB9 SNPs were genotyped in 316 subjects who had all undergone radiological examination. The association study was performed by both single-locus and haplotype-based analyses.


Bone & Joint Research
Vol. 3, Issue 9 | Pages 262 - 272
1 Sep 2014
Gumucio J Flood M Harning J Phan A Roche S Lynch E Bedi A Mendias C

Objectives

Rotator cuff tears are among the most common and debilitating upper extremity injuries. Chronic cuff tears result in atrophy and an infiltration of fat into the muscle, a condition commonly referred to as ‘fatty degeneration’. While stem cell therapies hold promise for the treatment of cuff tears, a suitable immunodeficient animal model that could be used to study human or other xenograft-based therapies for the treatment of rotator cuff injuries had not previously been identified.

Methods

A full-thickness, massive supraspinatus and infraspinatus tear was induced in adult T-cell deficient rats. We hypothesised that, compared with controls, 28 days after inducing a tear we would observe a decrease in muscle force production, an accumulation of type IIB fibres, and an upregulation in the expression of genes involved with muscle atrophy, fibrosis and inflammation.


Bone & Joint Research
Vol. 2, Issue 3 | Pages 58 - 65
1 Mar 2013
Johnson R Jameson SS Sanders RD Sargant NJ Muller SD Meek RMD Reed MR

Objectives

To review the current best surgical practice and detail a multi-disciplinary approach that could further reduce joint replacement infection.

Methods

Review of relevant literature indexed in PubMed.