A5012116326- Bone health and treatments
- Bone Metabolism and Diseases
- Metabolism and Genetic Disorders
- Cell Adhesion Molecules Research
- Pulmonary Hypertension Research and Treatments
- Congenital Heart Disease Studies
- Connective tissue disorders research
- Dermatological and Skeletal Disorders
- Biochemical and Molecular Research
- Porphyrin Metabolism and Disorders
- Autoimmune Bullous Skin Diseases
- Bone and Dental Protein Studies
- Mitochondrial Function and Pathology
- Diet and metabolism studies
- Genomic variations and chromosomal abnormalities
- Neurogenetic and Muscular Disorders Research
- Skin and Cellular Biology Research
- Nitric Oxide and Endothelin Effects
- Neonatal Health and Biochemistry
- Cutaneous lymphoproliferative disorders research
- Bone and Joint Diseases
- Cardiac Arrhythmias and Treatments
- Cardiac Valve Diseases and Treatments
- Urticaria and Related Conditions
- Pancreatitis Pathology and Treatment
University of Aberdeen
2010-2022
Institute of Medical Sciences
2011-2016
Therapeutics Clinical Research
2002
Heinrich Heine University Düsseldorf
2001
St Bartholomew's Hospital
1989-1994
University of Oulu
1991
Leiden University
1987-1991
University College London
1990
The bone remodelling cycle (see Poster panel "The cycle") maintains the integrity of skeleton through balanced activities its constituent cell types. These are bone-forming osteoblast, a that produces organic matrix and aids mineralisation (Karsenty et al., 2009); bone-degrading osteoclast, unique type exocrine dissolves mineral enzymatically degrades extracellular (ECM) proteins (Teitelbaum, 2007); osteocyte, an osteoblast-derived post-mitotic within acts as mechanosensor endocrine...
We have defined the structure of Osteoclast Functional Antigen (OFA) by immunological and biochemical means. OFA is an abundant surface antigen in human animal osteoclasts has been characterized previously monoclonal antibodies 13C2 23C6, one which mimicks inhibitory activity calcitonin on osteoclastic bone resorption. By following criteria we show that a member integrin family extracellular matrix receptors identical, or at least highly related, to vitronectin receptor (VNR) isolated from...
Abstract Bisphosphonates are the important class of antiresorptive drugs used in treatment metabolic bone diseases. Although their molecular mechanism action has not been fully elucidated, recent studies have shown that nitrogen-containing bisphosphonates can inhibit protein prenylation macrophages vitro. In this study, we show risedronate, zoledronate, ibandronate, alendronate, and pamidronate (but non clodronate, etidronate, tiludronate) prevent incorporation [14C]mevalonate into...
Nitric oxide (NO) has been reported to inhibit osteoclastic bone resorption, yet potent stimulators of such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), are known stimulate NO production. This paradox prompted us reinvestigate the relationship between production resorption in mouse calvarial organ cultures. Control cultures those stimulated with calciotropic hormones individual cytokines produced little NO, under these conditions synthase inhibitor, L-NG-monomethyl arginine...
Nitric oxide (NO) is a pleiotropic signaling molecule that produced by bone cells constitutively and in response to diverse stimuli such as proinflammatory cytokines, mechanical strain, sex hormones. Endothelial nitric synthase (eNOS) the predominant NOS isoform expressed bone, but its physiological role regulating metabolism remains unclear. Here we studied various aspects of female mice with targeted disruption eNOS gene. Mice deficiency (eNOS KO) had reduced mineral density, cortical...
This study illustrates that Plekhm1 is an essential protein for bone resorption, as loss-of-function mutations were found to underlie the osteopetrotic phenotype of incisors absent rat well intermediate type human osteopetrosis. Electron and confocal microscopic analysis demonstrated monocytes from a patient homozygous mutation differentiated into osteoclasts normally, but when cultured on dentine discs, failed form ruffled borders showed little evidence resorption. The presence both RUN...
Abstract The ligand binding ability of rat osteoclast adhesion receptors was investigated in an attachment assay using osteoclasts disaggregated from bone. Osteoclasts adhered well to the Arg-Gly-Asp (RGD)-containing proteins osteopontin (bone sialoprotein I) and BSP II), vitronectin, fibrinogen, von Willebrand factor, fibronectin. also adhered, but less strongly, type I collagen. No observed thrombospondin, tenascin, laminin, or a range non-RGD-containing bone other sources. all ligands...
Nitric oxide has been implicated as a mediator of inflammatory arthritis, and recent work shown that pro-inflammatory cytokines stimulate NO production in vitro by activation the inducible nitric synthase (iNOS) pathway. In order to identify cellular sources within joint, we have used immunohistochemical techniques study distribution iNOS synovium cartilage from normal diseased joints. was most strongly expressed synovial lining layer, subsynovium, vascular smooth muscle chondrocytes...
During bone resorption, osteoclasts form a tight attachment, the sealing zone, around resorption lacunae. Vitronectin receptor has previously been shown to be expressed in and it suggested that mediates attachment at zone. In this study we have glycine-arginine-glycine-aspartic acid-serine pentapeptide inhibits by isolated drastically changes morphology of osteoclasts. When vitronectin was localized immunofluorescence rat chicken cultured on slices, found distributed throughout osteoclast...
Osteogenesis imperfecta is an inherited disorder characterized by increased bone fragility, fractures, and osteoporosis, most cases are caused mutations affecting the type I collagen genes. Here, we describe a new mouse model for termed Aga2 (abnormal gait 2) that was isolated from Munich N-ethyl-N-nitrosourea mutagenesis program exhibited phenotypic variability, including reduced mass, multiple early lethality. The causal gene mapped to Chromosome 11 linkage analysis, C-terminal frameshift...
Abstract Imbalances between bone resorption and formation lie at the root of disorders such as osteoporosis, Paget's disease (PDB), osteopetrosis. Recently, genetic functional studies have implicated proteins involved in autophagic protein degradation important mediators cell function normal physiology pathology. Autophagy is conserved process whereby aggregated proteins, intracellular pathogens, damaged organelles are degraded recycled. This both for cellular quality control response to...
The study of osteoclast integrins has been previously hampered by the lack a source large numbers purified osteoclasts. Osteoclastoma, human giant cell tumor bone, supplied rich osteoclasts within tissue containing many diverse types. Osteoclastoma integrin immunostaining confirmed presence alpha v beta 3 complex and 2 1 subunits on However, weak expression, for example with 5, was difficult to interpret. Purification magnetic beads coated vitronectin receptor monoclonal antibody (13C2)...
Nitrogen-containing bisphosphonate drugs inhibit bone resorption by inhibiting FPP synthase and thereby preventing the synthesis of isoprenoid lipids required for protein prenylation in bone-resorbing osteoclasts. NE10790 is a phosphonocarboxylate analogue potent risedronate weak anti-resorptive agent. Although was poor inhibitor synthase, it did J774 macrophages osteoclasts, but only proteins molecular mass ∼22–26 kDa, which not affected peptidomimetic inhibitors either farnesyl transferase...
Abstract Recent work has shown that nitric oxide (NO) acts as an important mediator of the effects proinflammatory cytokines and mechanical strain in bone. Although several bone-derived cells have been to produce NO vitro, less is known about isoforms synthase (NOS), which are expressed bone or their cellular distribution. Here we investigated expression, localization, regulation NOS mRNA protein cultured tissue sections. We failed detect inducible (iNOS) normal using immunohistochemical...
Abstract Paget's disease of bone is a common characterized by increased and disorganized remodeling at focal sites throughout the skeleton. The etiology unresolved. A persistent viral infection has long been suggested to cause disease. Antigen and/or nucleic acid sequences paramyxoviruses (in particular measles virus [MV], canine distemper [CDV], respiratory syncytial [RSV]) have reported in pagetic number groups; however, others unable confirm this so far no isolated from patients. Here, we...