Previous genome-wide association studies (GWAS) have reported significant association of the single nucleotide polymorphism (SNP) rs8044769 in the fat mass and obesity-associated gene (FTO) with osteoarthritis (OA) risk in European populations. However, these findings have not been confirmed in Chinese populations. We systematically genotyped rs8044769 and evaluated the association between the genetic variants and OA risk in a case-controlled study including 196 OA cases and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform.Objectives
Methods
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 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.Objectives
Method
The long term biological effects of wear products
following total hip arthroplasty (THA) are unclear. However, the indications
for THA are expanding, with increasingly younger patients undergoing
the procedure. This prospective, randomised study compared two groups of patients
undergoing THA after being randomised to receive one of two different
bearing surfaces: metal-on-polyethylene (MoP) n = 22 and metal-on-metal
(MoM) n = 23. We investigated the relationship between three variables:
bearing surface (MoP Our results demonstrated significantly higher mean cobalt and
chromium (Co and Cr) blood levels in the MoM group at all follow-up
points following surgery (p <
0.01), but there were no significant
differences in the chromosomal aberration indices between MoM and
MoP at two or five years (two years: p = 0.56, p = 0.08, p = 0.91, p
= 0.51 and five years: p = 0.086, p = 0.73, p = 0.06, p = 0.34)
for translocations, breaks, loss and gain of chromosomes respectively.
Regression analysis showed a strong linear relationship between
Cr levels and the total chromosomal aberration indices in the MoM
group (R2 = 0.90016), but this was not as strong for
Co (R2 = 0.68991). In the MoP group, the analysis revealed
a poor relationship between Cr levels and the total chromosomal
aberration indices (R2 = 0.23908) but a slightly stronger
relationship for Co (R2 = 0.64292). Across both groups,
Spearman’s correlation detected no overall association between Co and Cr
levels and each of the studied chromosomal aberrations. There remains
no clear indication which THA bearing couple is the most biocompatible,
especially in young active patients. While THA continues to be very
successful at alleviating pain and restoring function, the long-term
biological implications of the procedure still require further scrutiny. Cite this article:
This study looked to analyse the expression levels of microRNA-140-3p and microRNA-140-5p in synovial fluid, and their correlations to the severity of disease regarding knee osteoarthritis (OA). Knee joint synovial fluid samples were collected from 45 patients with OA of the knee (15 mild, 15 moderate and 15 severe), ten healthy volunteers, ten patients with gouty arthritis, and ten with rheumatoid arthritis. The Kellgren–Lawrence grading (KLG) was used to assess the radiological severity of knee OA, and the patients were stratified into mild (KLG < 2), moderate (KLG = 2), and severe (KLG > 2). The expression of miR-140-3p and miR-140-5p of individual samples was measured by SYBR Green quantitative polymerase chain reaction (PCR) analysis. The expression of miR-140-3p and miR-140-5p was normalised to U6 internal control using the 2-△△CT method. All data were processed using SPSS software.Objectives
Methods
This article provides an overview of the role of genomics in sarcomas and describes how new methods of analysis and comparative screening have provided the potential to progress understanding and treatment of sarcoma. This article reviews genomic techniques, the evolution of the use of genomics in cancer, the current state of genomic analysis, and also provides an overview of the medical, social and economic implications of recent genomic advances.
Implant-associated infection is a major source
of morbidity in orthopaedic surgery. There has been extensive research
into the development of materials that prevent biofilm formation,
and hence, reduce the risk of infection. Silver nanoparticle technology
is receiving much interest in the field of orthopaedics for its
antimicrobial properties, and the results of studies to date are
encouraging. Antimicrobial effects have been seen when silver nanoparticles are
used in trauma implants, tumour prostheses, bone cement, and also
when combined with hydroxyapatite coatings. Although there are promising
results with Cite this article:
This study aimed to investigate the functional effects of microRNA (miR)-214-5p on osteoblastic cells, which might provide a potential role of miR-214-5p in bone fracture healing. Blood samples were obtained from patients with hand fracture or intra-articular calcaneal fracture and from healthy controls (HCs). Expression of miR-214-5p was monitored by qRT-PCR at day 7, 14 and 21 post-surgery. Mouse osteoblastic MC3T3-E1 cells were transfected with antisense oligonucleotides (ASO)-miR-214-5p, collagen type IV alpha 1 (COL4A1) vector or their controls; thereafter, cell viability, apoptotic rate, and the expression of collagen type I alpha 1 (COL1A1), type II collagen (COL-II), and type X collagen (COL-X) were determined. Luciferase reporter assay, qRT-PCR, and Western blot were performed to ascertain whether COL4A1 was a target of miR-214-5p.Objectives
Methods
We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy.Objectives
Materials and Methods
The number of arthroplasties being undertaken
is expected to grow year on year, and periprosthetic joint infections will
be an increasing socioeconomic burden. The challenge to prevent
and eradicate these infections has resulted in the emergence of
several new strategies, which are discussed in this review. Cite this article:
The objective of this study was to investigate the therapeutic effect of peripheral blood mononuclear cells (PBMNCs) treated with quality and quantity control culture (QQ-culture) to expand and fortify angiogenic cells on the acceleration of fracture healing. Human PBMNCs were cultured for seven days with the QQ-culture method using a serum-free medium containing five specific cytokines and growth factors. The QQ-cultured PBMNCs (QQMNCs) obtained were counted and characterised by flow cytometry and real-time polymerase chain reaction (RT-PCR). Angiogenic and osteo-inductive potentials were evaluated using tube formation assays and co-culture with mesenchymal stem cells with osteo-inductive medium Objectives
Methods
During open orthopaedic surgery, joints may be exposed to air, potentially leading to cartilage drying and chondrocyte death, however, the long-term effects of joint drying The patellar groove of anaesthetised rats was exposed (sham-operated), or exposed and then subjected to laminar airflow (0.25m/s; 60 minutes) before wounds were sutured and animals recovered. Animals were monitored for up to eight weeks and then sacrificed. Cartilage and chondrocyte properties were studied by histology and confocal microscopy, respectively.Objectives
Methods
This study aims to assess first, whether mutations in the epidermal
growth factor receptor (EGFR) and Kirsten rat sarcoma (kRAS) genes
are associated with overall survival (OS) in patients who present
with symptomatic bone metastases from non-small cell lung cancer
(NSCLC) and secondly, whether mutation status should be incorporated into
prognostic models that are used when deciding on the appropriate
palliative treatment for symptomatic bone metastases. We studied 139 patients with NSCLC treated between 2007 and 2014
for symptomatic bone metastases and whose mutation status was known.
The association between mutation status and overall survival was
analysed and the results applied to a recently published prognostic
model to determine whether including the mutation status would improve
its discriminatory power.Aims
Patients and Methods
Eukaryotic translation initiation factor 3 (eIF3) is a multi-subunit complex that plays a critical role in translation initiation. Expression levels of eIF3 subunits are elevated or decreased in various cancers, suggesting a role for eIF3 in tumorigenesis. Recent studies have shown that the expression of the eIF3b subunit is elevated in bladder and prostate cancer, and eIF3b silencing inhibited glioblastoma growth and induced cellular apoptosis. In this study, we investigated the role of eIF3b in the survival of osteosarcoma cells. To investigate the effect of eIF3b on cell viability and apoptosis in osteosarcoma cells, we first examined the silencing effect of eIF3b in U2OS cells. Cell viability and apoptosis were examined by the Cell Counting Kit-8 (CCK-8) assay and Western blot, respectively. We also performed gene profiling to identify genes affected by eIF3b silencing. Finally, the effect of eIF3b on cell viability and apoptosis was confirmed in multiple osteosarcoma cell lines.Objectives
Methods
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. 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 Objectives
Methods
The incidence of acute and chronic conditions
of the tendo Achillis appear to be increasing. Causation is multifactorial
but the role of inherited genetic elements and the influence of
environmental factors altering gene expression are increasingly
being recognised. Certain individuals’ tendons carry specific variations
of genetic sequence that may make them more susceptible to injury.
Alterations in the structure or relative amounts of the components
of tendon and fine control of activity within the extracellular
matrix affect the response of the tendon to loading with failure
in certain cases. This review summarises present knowledge of the influence of
genetic patterns on the pathology of the tendo Achillis, with a
focus on the possible biological mechanisms by which genetic factors
are involved in the aetiology of tendon pathology. Finally, we assess
potential future developments with both the opportunities and risks
that they may carry. Cite this article:
Triamcinolone acetonide (TA) is widely used for the treatment of rotator cuff injury because of its anti-inflammatory properties. However, TA can also produce deleterious effects such as tendon degeneration or rupture. These harmful effects could be prevented by the addition of platelet-rich plasma (PRP), however, the anti-inflammatory and anti-degenerative effects of the combined use of TA and PRP have not yet been made clear. The objective of this study was to determine how the combination of TA and PRP might influence the inflammation and degeneration of the rotator cuff by examining rotator cuff-derived cells induced by interleukin (IL)-1ß. Rotator cuff-derived cells were seeded under inflammatory stimulation conditions (with serum-free medium with 1 ng/ml IL-1ß for three hours), and then cultured in different media: serum-free (control group), serum-free + TA (0.1mg/ml) (TA group), serum-free + 10% PRP (PRP group), and serum-free + TA (0.1mg/ml) + 10% PRP (TA+PRP group). Cell morphology, cell viability, and expression of inflammatory and degenerative mediators were assessed.Objectives
Methods
The February 2014 Foot &
Ankle Roundup360 looks at: optimal medial malleolar fixation; resurfacing in the talus; predicting outcome in mobility ankles; whether mal-aligned ankles can be successfully replaced; cartilage colonisation in bipolar ankle grafts; CTs and proof of fusion; recalcitrant Achilles tendinopathy; and recurrent fifth metatarsal stress fractures.
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. 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.Objectives
Methods
