Sharon J Owen (nee Brown)

Robert Jones and Agnes Hunt Orthopaedic and District Hospital NHS Trust · Wolfson Centre for Inherited Neuromuscular Disease (CIND)

Structural, functional and molecular cardiac defects have been reported in spinal muscular atrophy (SMA) patients and mouse models. Previous quantitative proteomics analyses demonstrated widespread molecular defects in the severe Taiwanese SMA mouse model. Whether such changes are conserved across different mouse models, including less severe forms...

Spinal muscular atrophy (SMA) is a neuromuscular disease particularly characterised by degeneration of ventral motor neurons. Survival motor neuron (SMN) 1 gene mutations cause SMA, and gene addition strategies to replace the faulty SMN1 copy are a therapeutic option. We have developed a novel, codon-optimised hSMN1 transgene and produced integrati...

Mutations in LMNA, encoding nuclear envelope (NE) protein lamin A/C, can cause congenital muscular dystrophy (L-CMD), but the downstream molecular mechanisms that give rise to L-CMD are unclear. Using quantitative western blotting and immunofluorescence microscopy, we characterised the expression and localization of NE proteins during myoblast diff...

Most research to characterise the molecular consequences of spinal muscular atrophy (SMA) has focused on SMA I. Here, proteomic profiling of skin fibroblasts from severe (SMA I), intermediate (SMA II), and mild (SMA III) patients, alongside age-matched controls, was conducted using SWATH mass spectrometry analysis. Differentially expressed proteomi...

With the rising demand for improved COVID-19 disease monitoring and prognostic markers, studies have aimed to identify biomarkers using a range of screening methods. However, the selection of biomarkers for validation from large datasets may result in potentially important biomarkers being overlooked when datasets are considered in isolation. Here,...

Objective: The purpose of this study was to investigate whether a simple, biologically robust method for inducing calcification of degenerate intervertebral discs (IVD) could be developed to provide an alternative treatment for patients requiring spinal fusion. Design: Nucleus pulposus (NP) cells isolated from 14 human IVDs were cultured in mono...

Objective: To assess the phenotype of human articular chondrocytes cultured in normoxia (21% O2) or continuous hypoxia (2% O2). Design: Chondrocytes were extracted from patients undergoing total knee replacement (n = 5) and cultured in ~21% (normoxic chondrocytes, NC) and 2% (hypoxic chondrocytes, HC) oxygen in both monolayer and 3-dimensional (...

There is increasing interest in the identification of biomarkers that could predict neurological outcome following a spinal cord injury (SCI). Although initial American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade is a good indicator of neurological outcome, for the patient and clinicians, an element of uncertainty remains. This pr...

The aim of this study was to examine the complexity of the stem cell populations in the intervertebral disc (IVD) and understand their role in disc degeneration with a view to determining whether the resident stem cells could be developed for therapeutic purposes to combat IVD degeneration. Stem cells have been isolated from disc and paradiscal tis...

Purpose To investigate the microscopic fibrous integration between the intervertebral disc, cartilage endplates and vertebral endplates in human lumbar spines of varying degrees of degeneration using differential interference contrast (DIC) optics. Weakness at these junctions is considered to be an important factor in the aetiology of disc herniati...

Study design: Review study. Objectives: The identification of prognostic biomarkers of spinal cord injury (SCI) will help to assign SCI patients to the correct treatment and rehabilitation regimes. Further, the detection of biomarkers that predict permanent neurological outcome would aid in appropriate recruitment of patients into clinical trial...

The present study reports the perplexing results that came about because of seriously impure commercially available reagents. Commercial reagents and chemicals are routinely ordered by scientists and expected to have been rigorously assessed for their purity. Unfortunately, we found this assumption to be risky. Extensive work was carried out within...

Mesenchymal stromal cells (MSC) can be isolated from several regions of human umbilical cords, including Wharton's jelly (WJ), artery, vein or cord lining. These MSC appear to be immune privileged and are promising candidates for cell therapy. However, isolating MSC from WJ, artery, vein or cord lining requires time-consuming tissue dissection. MSC...

Background: The intervertebral disc (IVD) is a complex cartilaginous structure which functions to resist biomechanical loads during spinal movement. It consists of the highly viscous cartilaginous nucleus pulposus, which is surrounded laterally by a thick outer ring of fibrous cartilage-the annulus fibrosus-and sandwiched inferiorly and superiorly...

The intervertebral disc (IVD) is composed of matrix molecules - collagen, proteoglycans, elastin and glycoproteins - which, by virtue of their biochemistry and specific organisation, allow the tissue to perform its mechanical function. This review provides a comprehensive description of the chemical make-up of the tissue and the proteases involved...

Proteoglycans are important to the functioning of the intervertebral disc. In addition to aggrecan there are the small leucine-rich proteoglycans (SLRPs). These are less common but in other locations their functions include collagen organisation, sequestering growth factors and stimulating inflammation. We have performed a comparative analysis of t...

Intervertebral disc (IVD) cells within the annulus fibrosus (AF) and nucleus pulposus (NP) maintain distinct functional extracellular matrices and operate within a potentially noxious and stressful environment. How disc cells respond to stress and whether stress is responsible for triggering degeneration is unknown. Disc cell proliferation and clus...

In osteoarthritis cancellous bone adapts to meet altered mechanical loading. These changes may be mediated by insulin-like growth factors (IGF-I and IGF-II), but the matrix bound binding protein, IGFBP-5 has not been investigated. To measure IGF-I, IGF-II, and IGFBP-5 in femoral head bone from non-OA controls and patients with OA, and to relate the...

Osteoarthritis (OA) is a debilitating condition common among the aging population. In this study we have determined mechanical and material properties of cancellous bone cores from two differently loaded regions of femoral heads obtained from healthy subjects and those with end-stage osteoarthritis. Densitometric properties were determined prior to...

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Appendix 2 is not included as it is two published journal articles Osteoarthritis (OA) is a common musculoskeletal disability and represents a major health burden to society. Pathological changes are found in all tissues of the joint; however studies on bone are few. The aims of this thesis were to characterize some of the densitometric, mechanical...