To explore the novel molecular mechanisms of histone deacetylase 4 (HDAC4) in chondrocytes via RNA sequencing (RNA-seq) analysis. Empty adenovirus (EP) and a Aims
Methods
Osteoarthritis (OA) is the most prevalent joint disease. However, the specific and definitive genetic mechanisms of OA are still unclear. Tissue-related transcriptome-wide association studies (TWAS) of hip OA and knee OA were performed utilizing the genome-wide association study (GWAS) data of hip OA and knee OA (including 2,396 hospital-diagnosed hip OA patients versus 9,593 controls, and 4,462 hospital-diagnosed knee OA patients versus 17,885 controls) and gene expression reference to skeletal muscle and blood. The OA-associated genes identified by TWAS were further compared with the differentially expressed genes detected by the messenger RNA (mRNA) expression profiles of hip OA and knee OA. Functional enrichment and annotation analysis of identified genes was performed by the DAVID and FUMAGWAS tools.Aims
Methods
Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage. Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California). Other independent genome-wide mRNA expression profiles of articular cartilage from three patients with OA and three healthy controls were obtained from the Gene Expression Omnibus (GEO) database. Integrative pathway enrichment analysis of DNA methylation and mRNA expression profiles was performed using integrated analysis of cross-platform microarray and pathway software. Gene ontology (GO) analysis was conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID).Aim
Patients and Methods
The proteoglycan aggrecan is a major component of the cartilaginous matrices which provides resistance against compressive forces. Spontaneously occurring functional null mutations in the aggrecan gene (Acan) in various species lead to perinatal chondrodysplasia. The aim of the present study was to investigate the cellular and biomechanical properties of the cartilaginous growth plate, and the development of intervertebral disc in a novel, experimentally induced aggrecan mutant mouse strain carrying an insertion in exon 5 of the The novel aggrecan mutant mice were generated by inserting a loxP site into exon 5 (E5i) by homologous recombination in ES cells. Wild type and homozygous mutant (Introduction
Methods
Pedicle-lengthening osteotomy is a novel surgery for lumbar spinal stenosis (LSS), which achieves substantial enlargement of the spinal canal by expansion of the bilateral pedicle osteotomy sites. Few studies have evaluated the impact of this new surgery on spinal canal volume (SCV) and neural foramen dimension (NFD) in three different types of LSS patients. CT scans were performed on 36 LSS patients (12 central canal stenosis (CCS), 12 lateral recess stenosis (LRS), and 12 foraminal stenosis (FS)) at L4-L5, and on 12 normal (control) subjects. Mimics 14.01 workstation was used to reconstruct 3D models of the L4-L5 vertebrae and discs. SCV and NFD were measured after 1 mm, 2 mm, 3 mm, 4 mm, or 5 mm pedicle-lengthening osteotomies at L4 and/or L5. One-way analysis of variance was used to examine between-group differences.Objectives
Methods
This study aimed to determine the relationship between pedicle-lengthening
distance and bulge-canal volume ratio in cases of lumbar spinal
stenosis, to provide a theoretical basis for the extent of lengthening
in pedicle-lengthening osteotomies. Three-dimensional reconstructions of CT images were performed
for 69 patients (33 men and 36 women) (mean age 49.96 years; 24
to 81). Simulated pedicle-lengthening osteotomies and disc bulge
and spinal canal volume calculations were performed using Mimics
software. Aims
Methods
Osteonecrosis of femoral head is well known and recognised complication in Sickle cell disease patients. Due to the severity of the Osteonecrosis, hip pain is major limiting factor for these patients requiring total hip arthroplasty in relatively young age. We studied and report our results in total hip arthroplasty of sickle cell patients. We studied 80 patients from our combined Orthopaedic & Haematology Sickle cell clinic. Twenty four patients had painful Osteonecrosis with secondary osteoarthritis of hip and underwent total hip arthroplasty. Three patients had bilateral hip replacements. A total of twenty seven replacements were studied retrospectively. 19 patients had uncemented (Corail/Pinnacle), 5 patients had hybrid(Pinnacle/Exeter) and 3 patients had cemented(Exeter) total hip arthroplasties respectively. The patients were serially followed up for clinical and radiological assessments for loosening. Oxford hip score (OHS) was used to assess the functional outcome. The average age of the patients at the time of surgery was 38.4 (Range – 20 to 59 years. The average follow up was 5.1 years (Range – 6 months to 10 years). There were 13 female and 11 male patients. The average oxford hip score was 38.07 with 10% infection rate and 11% aseptic loosening. Arthroplasties carry high risk in patients with sickle cell disease. We report lower rates of infection and loosening rates compared to the earlier studies. Combined Haematological and Orthopaedic team input is optimal during assessment, surgery, peri-operative period and follow up. Our results of total hip replacements in sickle cell disease patients are good.
The aim of this retrospective study was to evaluate the failure rate among different fixation devices for undisplaced fracture neck of femur. All 52 patients with Garden I and II hip fractures who underwent surgery in a teaching hospital in London from January 2007 to June 2012 were included. Electronic patient records were accessed to collect the patient data. There were 52% females and the mean age of patients was 70 years. Thirty patients had cannulated screws, 18 – dynamic hip screw (DHS) with de-rotation screw and 4 had DHS alone. Initial results showed that 36% patients had re-operation. 7(77%) had total hip replacement and 1(11%) had metal work removal. The reason for revision was failure of fixation in 8 (88%) and avascular necrosis in 1 (11%). There was significantly higher failure rate in the DHS with derotation screw group (50%) compared to the cannulated screw group (35%) and the DHS alone group (0%). Average time to planned revision was 11.1 months. Traditionally undisplaced intra capsular hip fractures are treated by in-situ fixation using different devices. Biomechanically DHS with de-rotation screw achieves better rotational and axial stability compared to other fixation devices. However, our study showed a higher failure rate in this group. Inability to achieve a perfectly parallel screw position seems to be a significant factor responsible for high failure. Higher failure rates with fixation may boost the role of replacement arthroplasty as one off surgical treatment in elderly patients.
Hip simulator studies have shown reduced hip offset can cause microseparation and increased wear in hard-on-hard hip bearings. However this has not been analysed yet in vivo. We studied the effect of reduced hip offset on serum metal ion levels in patients with metal-on-metal (MoM) hip arthroplasty. From all patients who underwent unilateral MoM bearing hip arthroplasty between 2005 and 2009, 63 patients had complete clinical evaluation, measurement of serum chromium and cobalt ion levels as well as biomechanical measurements on pre- and post operative radiographs (cup inclination, head inclination, change in hip offset and change in hip length.) Ten arthroplasties were revised due to adverse metal reaction and six patients awaiting revision. 55% of ASR hips showed higher metal ions (>7 ppb) whereas only 15% of non-ASR hips had higher ion levels. Patients with reduced postoperative hip offset by more than 5 mm had significantly higher mean metal ion levels compared to the the rest of the hips (31.8 ppb vs. 7.4 ppb, p=0.002). On subgroup analysis this effect was present in non-ASR hips (18.7 ppb vs. 4.7 ppb, p=0.025) but was not significant in ASR hips (29.6 ppb vs. 16.3 ppb, p=0.347). Our study demonstrated significantly higher serum metal ion levels in patients who lost more than 5 mm hip offset after arthroplasty. Reduced soft tissue tension leading to microseparation of the articulation and edge loading is a theoretical explanation for this effect. This may be relevant in other hard bearings such as ceramic-on-ceramic as well.
3D porous and nano-structured polyetheretherketone (PEEK) surface embedded with biofunctional groups can not only induce the up-regulation of osteogenic genes and proteins Porous biomaterials with three-dimensional (3D) surface structure can enhance biological functionalities especially in bone tissue engineering. Many techniques have hitherto been utilised to fabricate porous structures on metal surfaces, including machining, shotblasting, anodic oxidation, alkali treatment and acid-etching. However, it has been difficult to accomplish this on polyetheretherketone (PEEK) due to its inherent chemical inertness. In this study, we have applied a method comprising of sulfonation and water immersion to establish a 3D porous and nanostructured network on the PEEK surface. This newly established 3D network embedded with bio-functional groups can help promote new bone formation Summary Statement
Introduction
There is little in the literature reporting on the incidence of heterotopic ossification (HO) after hip resurfacing arthroplasty. HO has long been recognized as a complication of THA, with a reported incidence that ranges between 5 – 90 %. We investigated the incidence of HO in a group of hip resurfacing patients, and compared this against the incidence of HO in a comparable group of patients managed with a conventional THA. We retrospectively reviewed patients who had a hip resurfacing procedure from January 2004 to December 2007 carried out by a single surgeon. To act as our comparative group, we selected a closely matched group of patients in terms of age and sex who underwent a THA over the same time period, under the same surgeon. 47 cases of resurfacing, 23 were female and 24 male. The 47 cases of the selected THA group consisted of 24 females and 23 males. Therefore the two groups were of a similar sex make up. Within the resurfacing group of patients, the ages ranged from 31 to 68 years, with the mean being 55.4 years, and the median being 56.5 years. The THA group possessed an age range of from 31 to 68 years, with the mean being 55.4 years, and the median being 56.5 years. The resurfacing group of patients had 5 cases showing HO, giving an overall rate of 10.6 percent. 3 were of the grade I variety, while 2 were grade II. The THA group had 6 cases showing HO, giving an overall rate of 12.8 percent. 5 of these were of the grade I variety, while 1 was of the grade III variety. We used a two tailed Fischer’s Exact test set at the 5th percentile significance level to compare the overall rate of HO occurrence between the 2 groups, namely 10.6 percent versus 12.8 percent. This gave a p value of 0.238. Therefore we can state that there is no significant difference in the rate of HO formation between the resurfacing and THA patients.
To investigate the proportion of dysplastic hips which are retroverted. We studied the radiographs of over seven hundred patients with dysplastic hips who had had a periacetabular osteotomy in the period 1984–1998. We excluded patients with neuromuscular dysplasia, Perthes’ disease of the hip, post-traumatic dysplasia and proximal focal femoral deficiency. We selected 232 radiographs of patients with congenital acetabular dysplasia. A number of parameters were measured including lateral centre-edge angle, anterior centre-edge angle, acetabular index of weight-bearing surface, femoral head extrusion index and acetabular index of depth to width. Also recorded were acetabular version and congruency between femoral head and acetabulum. The lateral centre-edge angle of Wiberg had a mean value of 6.4° (SD 8.9°), the mean anterior centre-edge angle was 1.3° (SD 13.5°) and the acetabular index of weight-bearing surface of the acetabulum had a mean value of 24.5° (SD 9.7°). The majority (192, 82.8%) of acetabula were anteverted as might be expected. However, a significant minority (40, 17.2%) were retroverted. The mean anterior centre-edge angle in retroverted hips was 6.7° (SD 9.4°) compared with 0.4° (SD 13.3°) in anteverted hips. The authors have shown that, in a typical group of patients with congenital acetabular dysplasia significant enough to warrant periacetabular osteotomy, the majority of hips as expected have anteverted acetabula. However, a significant minority are retroverted. This finding has an important bearing on the performance of the osteotomy. We have also found that most if not all the information required prior to and following periac-etabular osteotomy can be obtained from an orthograde view of the pelvis.
Discogenic low back pain is a common cause of disability, but its pathogenesis is poorly understood. We collected 19 specimens of lumbar intervertebral discs from 17 patients with discogenic low back pain during posterior lumbar interbody fusion, 12 from physiologically ageing discs and ten from normal control discs. We investigated the histological features and assessed the immunoreactive activity of neurofilament (NF200) and neuropeptides such as substance P (SP) and vasoactive-intestinal peptide (VIP) in the nerve fibres. The distinct histological characteristic of the painful disc was the formation of a zone of vascularised granulation tissue from the nucleus pulposus to the outer part of the annulus fibrosus along the edges of the fissures. SP-, NF- and VIP-immunoreactive nerve fibres in the painful discs were more extensive than in the control discs. Growth of nerves deep into the annulus fibrosus and nucleus pulposus was observed mainly along the zone of granulation tissue in the painful discs. This suggests that the zone of granulation tissue with extensive innervation along the tears in the posterior part of the painful disc may be responsible for causing the pain of discography and of discogenic low back pain.
It is generally agreed that in acetabular dysplasia the acetabulum lies excessively anteverted. Although this is true for the majority of hips, we have found that in some patients with dysplastic hips, the acetabulum lies unexpectedly in retroversion.
The optimal method of prophylaxis against venous thromboembolism after total hip replacement (THR) remains uncertain. Most surgeons use some form of pharmacological prophylaxis, most commonly heparin. The precise balance of the benefits and risks is unclear, and serious complications can occur. We describe a case of heparin-induced thrombocytopenia and thrombosis syndrome in a 62-year-old woman after THR.
Infection of human cartilage with HIV in vivo has not previously been reported. Specimens of articular cartilage taken at postmortem from ten patients who were HIV-positive were examined. Two had AIDS and eight were believed to have stage-2 disease. The standard polymerase chain reaction (PCR) protocol was modified to allow semiquantitative analysis of the samples. Oligonucleotide primers labelled with 32P gamma-ATP were used to detect a segment of HIV DNA and a control DNA gene segment (HLA genome) to estimate the ratio of infected cells. The 32P-labelled PCR products were separated on acrylamide gels and visualised directly by autoradiography and computer densitometry. Infection of human cartilage in vivo was demonstrated in nine of the ten samples in which the PCR analysis was positive. The other did not react sufficiently to produce detectable radiolabelled PCR product despite repeated DNA digestion and extraction. Cartilage infected with HIV could be a potential source of HIV when used in operations.
The early diagnosis of aseptic loosening of a total hip replacement by plain radiography, scintigraphy and arthrography has been shown to be unreliable. It has been suggested that it may be possible to distinguish between a secure and a loose prosthesis using a vibration technique. We have assessed the use of this technique in vitro using models of early and late loosening. Late loosening with an unstable prosthesis can be reliably detected by vibration analysis, but this method was shown to have a very poor diagnostic sensitivity in early loosening when there is no obvious prosthetic instability.
