A5085418278- Bone health and treatments
- Bone Metabolism and Diseases
- Cancer-related Molecular Pathways
- Bone and Joint Diseases
- Bone health and osteoporosis research
- Fibroblast Growth Factor Research
- Connective tissue disorders research
- Cytokine Signaling Pathways and Interactions
- Osteomyelitis and Bone Disorders Research
- Mitochondrial Function and Pathology
- Proteoglycans and glycosaminoglycans research
- Medical Imaging and Pathology Studies
- Rheumatoid Arthritis Research and Therapies
- Cancer and Skin Lesions
- Metabolism and Genetic Disorders
- Oral health in cancer treatment
- NF-κB Signaling Pathways
- Ubiquitin and proteasome pathways
- Biomarkers in Disease Mechanisms
- Autophagy in Disease and Therapy
- Organophosphorus compounds synthesis
- Toxoplasma gondii Research Studies
- Amino Acid Enzymes and Metabolism
- Cellular Mechanics and Interactions
- Health and Medical Studies
University of Liverpool
1999-2022
Aintree University Hospitals NHS Foundation Trust
2021
Royal Liverpool and Broadgreen University Hospital NHS Trust
2015-2019
National Health Service
2019
Royal Liverpool University Hospital
1999-2018
University of Edinburgh
2006-2017
Institute of Genetics and Cancer
2012-2017
Amgen (United Kingdom)
2012
Universities UK
2012
NHS Lothian
2010
Mutations of SQSTM1 occur in about10% patients with Paget's disease bone (PDB), but it is unclear whether they play a causal role or regulate susceptibility to an environmental trigger. Here we show that mice proline leucine mutation at codon 394 mouse sqstm1 (P394L), equivalent the P392L humans, develop disorder remarkable similarity PDB. The P394L mutant developed focal lesions increasing age and by 12 months, 14/18 (77%) heterozygotes 20/21 (95%) homozygotes had lesions, compared 0/18...
Abstract Three novel missense mutations of SQSTM1 were identified in familial PDB, all affecting the UBA domain. Functional and structural analysis showed that disease severity was related to type mutation but unrelated polyubiquitin-binding properties mutant domain peptides. Introduction: Mutations ubiquitin-associated (UBA) Sequestosome 1 (SQSTM1) gene have recently been as a common cause Paget's bone (PDB), mechanisms responsible are unclear. We three conducted functional analyses...
Micro-CT analysis has become the standard method for assessing bone volume and architecture in small animals. However, micro-CT does not allow assessment of turnover parameters such as formation rate osteoclast (OC) number surface. For these crucial variables histomorphometric is still an essential technique. Histomorphometry however, time consuming and, especially mouse bones, OCs can be difficult to detect. The main purpose this study was develop validate a relatively easy rapid measure...
Abstract We studied the role of TNFRSF11B polymorphisms on risk to develop Paget's disease bone in a Belgian study population. observed no association men, but highly significant was found women, and this confirmed population from United Kingdom. Introduction: Juvenile has been shown be caused by mutations encoding osteoprotegerin. Although gene have never patients with typical (PDB), there are indications that might contribute developing PDB. Materials Methods: recruited 131 sporadic PDB...
Abstract To clarify the role of TNFRSF11B gene encoding osteoprotegerin (OPG), in Paget's disease bone (PDB) we studied polymorphisms an association study 690 UK subjects and a worldwide familial 66 kindreds. We found that G1181 allele TNFRSF11B, lysine at codon 3 OPG protein, predisposes to both sporadic PDB. Introduction: is common disorder characterized by focal abnormalities turnover. Genetic factors are important pathogenesis PDB, studies have shown inactivating mutations gene, cause...
Abstract RANK (receptor activator of nuclear factor-κB), encoded by TNFRSF11A, is a key protein in osteoclastogenesis. TNFRSF11A mutations cause Paget's disease bone (PDB)–like diseases (ie, familial expansile osteolysis, skeletal hyperphosphatasia, and early-onset PDB) an osteoclast-poor form osteopetrosis. However, no have been found classic PDB, neither nor isolated cases. To investigate the possible relationship between polymorphisms sporadic we conducted association study including 32...
Paget’s disease of bone (PDB) is a chronic skeletal disorder that can affect one or several bones in individuals older than 55 y age. PDB-like changes have been reported archaeological remains as old Roman, although accurate diagnosis and natural history the lacking. Six skeletons from collection 130 excavated at Norton Priory North West England, which dates to medieval times, show atypical extensive pathological resembling contemporary PDB affecting many 75% individual skeletons. Disease...
Abstract Mutations in the UBA domain of SQSTM1 are a common cause Paget's disease bone. Here we show that most disease-causing mutation (P392L) is carried on shared haplotype, consistent with founder effect and ancestral origin. Introduction: bone (PDB) condition strong genetic component. affecting ubiquitin-associated (UBA) sequestosome 1 (SQSTM1) have recently been shown to be an important PDB. The results proline leucine amino acid change at codon 392 (P392L), evidence has presented...
Objectives To identify genetic determinants of susceptibility to clinical vertebral fractures, which is an important complication osteoporosis. Methods Here we conduct a genome-wide association study in 1553 postmenopausal women with fractures and 4340 controls, two-stage replication involving 1028 cases 3762 controls. Potentially causal variants were identified using expression quantitative trait loci (eQTL) data from transiliac bone biopsies bioinformatic studies. Results A locus tagged by...
Alkaptonuria is a rare genetic disorder characterized by high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it deposited in connective tissue as pigmented polymer. In an observational study carried out National AKU Centre (NAC) Liverpool, total thirty-nine patients attended yearly visits varying numbers. At each visit mixture clinical, joint and spinal assessments were the results calculated yield AKUSSI (Alkaptonuria Severity Score Index),...
Abstract Osteoporosis is the most common age‐related metabolic bone disorder, which characterized by low mass and deterioration in architecture, with a propensity to fragility fractures. The best treatment for osteoporosis relies on stimulation of osteoblasts form new restore structure, however, anabolic therapeutics are few their use time restricted. Here, we report that Syndecan‐3 increases formation through enhancement WNT signaling osteoblasts. Young adult Sdc3 −/− mice have volume,...
Extracellular signal-regulated protein kinase 5 (ERK5) has been implicated during development and carcinogenesis. Nkx3.1-mediated Cre expression is a useful strategy to genetically manipulate the mouse prostate. While grossly normal at birth, we observed an unexpected phenotype of spinal protrusion in Nkx3.1:Cre;Erk5
ABSTRACT Paget's disease of bone (PDB) is an age-related metabolic disorder, characterised by focally increased and disorganised remodelling initiated abnormal hyperactive osteoclasts. The germline P392L mutation SQSTM1 (encoding p62) a strong genetic risk factor for PDB in humans, the equivalent mice (P394L) causes PDB-like disorder. However, it unclear why pagetic lesions become more common with age. Here, we assessed effect p62 P394L on osteoclastogenesis morphometry relation to ageing,...
Paget's disease of bone (PDB) is characterized by focal increases in remodelling. Genome-wide association studies identified a susceptibility locus for PDB tagged rs5742915, which located within the PML gene. Here, we have assessed candidacy as predisposing gene at this locus. We found that PDB-risk allele rs5742915 was associated with lower expression and blood cells from individuals than controls. The differentiation, survival resorptive activity osteoclasts prepared Pml-/- mice increased...
Summary Hypercalcaemia as the only manifestation of B-cell lymphoma is seen very rarely. Its pathophysiology heterogenous and not well understood. We report a 73-year-old man who presented with severe hypercalcaemia before any signs malignancy became evident. He was diagnosed on bone marrow trephine biopsy. The associated high plasma concentrations parathyroid-hormone-related protein, interleukin-6 tumour necrosis factor. Our patient had markedly increased osteoclast osteoblast activity...
Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)