Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model. The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA).Aims
Methods
Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining.Aims
Methods
The aim of this study was to determine the extent to which patient demographics, clinical presentation, and blood parameters vary in A prospective case series was undertaken at a single UK paediatric institution between October 2012 and November 2018 of all patients referred with suspected septic arthritis. We recorded the clinical, biochemical, and microbiological findings in all patients.Aims
Methods
Tenosynovial giant cell tumour (TGCT) is one of the most common soft-tissue tumours of the foot and ankle and can behave in a locally aggressive manner. Tumour control can be difficult, despite the various methods of treatment available. Since treatment guidelines are lacking, the aim of this study was to review the multidisciplinary management by presenting the largest series of TGCT of the foot and ankle to date from two specialized sarcoma centres. The Oxford Tumour Registry and the Leiden University Medical Centre Sarcoma Registry were retrospectively reviewed for patients with histologically proven foot and ankle TGCT diagnosed between January 2002 and August 2019.Aims
Methods
This study aimed to investigate whether human umbilical cord mesenchymal stem cells (UC-MSCs) can prevent articular cartilage degradation and explore the underlying mechanisms in a rat osteoarthritis (OA) model induced by monosodium iodoacetate (MIA). Human UC-MSCs were characterized by their phenotype and multilineage differentiation potential. Two weeks after MIA induction in rats, human UC-MSCs were intra-articularly injected once a week for three weeks. The therapeutic effect of human UC-MSCs was evaluated by haematoxylin and eosin, toluidine blue, Safranin-O/Fast green staining, and Mankin scores. Markers of joint cartilage injury and pro- and anti-inflammatory markers were detected by immunohistochemistry.Aims
Methods
Rheumatoid arthritis (RA) is a systematic autoimmune disorder, characterized by synovial inflammation, bone and cartilage destruction, and disease involvement in multiple organs. Although numerous drugs are employed in RA treatment, some respond little and suffer from severe side effects. This study aimed to screen the candidate therapeutic targets and promising drugs in a novel method. We developed a module-based and cumulatively scoring approach that is a deeper-layer application of weighted gene co-expression network (WGCNA) and connectivity map (CMap) based on the high-throughput datasets.Aims
Methods
The lack of disease-modifying treatments for osteoarthritis (OA) is linked to a shortage of suitable biomarkers. This study combines multi-molecule synovial fluid analysis with machine learning to produce an accurate diagnostic biomarker model for end-stage knee OA (esOA). Synovial fluid (SF) from patients with esOA, non-OA knee injury, and inflammatory knee arthritis were analyzed for 35 potential markers using immunoassays. Partial least square discriminant analysis (PLS-DA) was used to derive a biomarker model for cohort classification. The ability of the biomarker model to diagnose esOA was validated by identical wide-spectrum SF analysis of a test cohort of ten patients with esOA.Aims
Methods
In this study, we compared the pain behaviour and osteoarthritis (OA) progression between anterior cruciate ligament transection (ACLT) and osteochondral injury in surgically-induced OA rat models. OA was induced in the knee joints of male Wistar rats using transection of the ACL or induction of osteochondral injury. Changes in the percentage of high limb weight distribution (%HLWD) on the operated hind limb were used to determine the pain behaviour in these models. The development of OA was assessed and compared using a histological evaluation based on the Osteoarthritis Research Society International (OARSI) cartilage OA histopathology score.Objectives
Methods
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. 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.Objectives
Methods
Bovine cartilage explants were cultured with isogenic Objectives
Methods
The aim of this retrospective study was to compare the functional
and radiological outcomes of bridge plating, screw fixation, and
a combination of both methods for the treatment of Lisfranc fracture
dislocations. A total of 108 patients were treated for a Lisfranc fracture
dislocation over a period of nine years. Of these, 38 underwent
transarticular screw fixation, 45 dorsal bridge plating, and 25
a combination technique. Injuries were assessed preoperatively according
to the Myerson classification system. The outcome measures included
the American Orthopaedic Foot and Ankle Society (AOFAS) score, the
validated Manchester Oxford Foot Questionnaire (MOXFQ) functional
tool, and the radiological Wilppula classification of anatomical
reduction.Aims
Patients and Methods
Osteoarthritis (OA) is an important cause of
pain, disability and economic loss in humans, and is similarly important in
the horse. Recent knowledge on post-traumatic OA has suggested opportunities
for early intervention, but it is difficult to identify the appropriate
time of these interventions. The horse provides two useful mechanisms
to answer these questions: 1) extensive experience with clinical
OA in horses; and 2) use of a consistently predictable model of
OA that can help study early pathobiological events, define targets
for therapeutic intervention and then test these putative therapies.
This paper summarises the syndromes of clinical OA in horses including
pathogenesis, diagnosis and treatment, and details controlled studies
of various treatment options using an equine model of clinical OA.
To assess the clinical and cost-effectiveness of a virtual fracture clinic (VFC) model, and supplement the literature regarding this service as recommended by The National Institute for Health and Care Excellence (NICE) and the British Orthopaedic Association (BOA). This was a retrospective study including all patients (17 116) referred to fracture clinics in a London District General Hospital from May 2013 to April 2016, using hospital-level data. We used interrupted time series analysis with segmented regression, and direct before-and-after comparison, to study the impact of VFCs introduced in December 2014 on six clinical parameters and on local Clinical Commissioning Group (CCG) spend. Student’s Objectives
Methods
Our aim was to examine the clinical and radiographic outcomes
in 257 consecutive Oxford unicompartmental knee arthroplasties (OUKAs)
(238 patients), five years post-operatively. A retrospective evaluation was undertaken of patients treated
between April 2008 and October 2010 in a regional centre by two
non-designing surgeons with no previous experience of UKAs. The
Oxford Knee Scores (OKSs) were recorded and fluoroscopically aligned
radiographs were assessed post-operatively at one and five years.Aims
Patients and Methods
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
Although infrequent, a fracture of the cuboid can lead to significant
disruption of the integrity of the midfoot and its function. The
purpose of this study was to classify the pattern of fractures of
the cuboid, relate them to the mechanism of injury and suggest methods
of managing them. We performed a retrospective review of patients with radiologically
reported cuboid fractures. Fractures were grouped according to commonly
occurring patterns of injury. A total of 192 fractures in 188 patients
were included. They were classified into five patterns of injury.Aims
Patients and Methods
