A5011835558- Alkaline Phosphatase Research Studies
- Bone Metabolism and Diseases
- Bone health and treatments
- Osteoarthritis Treatment and Mechanisms
- Parathyroid Disorders and Treatments
- Growth Hormone and Insulin-like Growth Factors
- Connective tissue disorders research
- Cytokine Signaling Pathways and Interactions
- Bone and Dental Protein Studies
- Heterotopic Ossification and Related Conditions
- Bone health and osteoporosis research
- Cell Adhesion Molecules Research
- Cancer, Hypoxia, and Metabolism
- Vitamin D Research Studies
- Dermatological and Skeletal Disorders
- Fibroblast Growth Factor Research
- Biotin and Related Studies
- Bone and Joint Diseases
- Adipose Tissue and Metabolism
- Proteoglycans and glycosaminoglycans research
- Trace Elements in Health
- Inflammatory mediators and NSAID effects
- NF-κB Signaling Pathways
- Protease and Inhibitor Mechanisms
- Immune Response and Inflammation
Roslin Institute
2016-2025
University of Edinburgh
2016-2025
Memorial University of Newfoundland
2023
Royal Veterinary College
2013-2022
University College London
2016-2022
University of Birmingham
2020-2022
Centre for Life
2022
Reservoir Labs (United States)
2021
Time Domain (United States)
2021
Orthopaedic Hospital
2016-2019
Western blotting has been a key technique for determining the relative expression of proteins within complex biological samples since first publications in 1979. Recent developments sensitive fluorescent labels, with truly quantifiable linear ranges and greater limits detection, have allowed biologists to probe tissue specific pathways processes higher resolution than ever before. However, application quantitative (QWB) range healthy tissues those from degenerative models highlighted problem...
Background Vascular calcification is an indicator of elevated cardiovascular risk. smooth muscle cells (VSMCs), the predominant cell type involved in medial vascular calcification, can undergo phenotypic transition to both osteoblastic and chondrocytic within a calcifying environment. Methodology/Principal Findings In present study, using vitro VSMC studies conjunction with ex vivo analyses mouse model we show that also associated expression osteocyte phenotype markers. As controls, terminal...
Endochondral ossification is a carefully orchestrated process mediated by promoters and inhibitors of mineralization. Phosphatases are implicated, but their identities functions remain unclear. Alkaline phosphatase (TNAP) plays crucial role promoting mineralization the extracellular matrix restricting concentration calcification inhibitor inorganic pyrophosphate (PP(i)). Mutations in TNAP gene cause hypophosphatasia, heritable form rickets osteomalacia. Here we show that PHOSPHO1, with...
Abstract PHOSPHO1 is a phosphatase highly expressed in bone. We studied its functional involvement mineralization through the use of novel small molecule inhibitors. expression was present within matrix vesicles, and inhibition enzyme action caused decrease ability vesicles to calcify. Introduction: The phosphatase, PHOSPHO1, belongs haloacid dehalogenase superfamily hydrolases capable cleaving phosphoethanolamine (PEA) phosphocholine generate inorganic phosphate. Our aims this study were...
During the process of endochondral bone formation, chondrocytes and osteoblasts mineralize their extracellular matrix by promoting formation hydroxyapatite seed crystals in sheltered interior membrane-limited vesicles (MVs). Here, we have studied phosphosubstrate catalysis osteoblast-derived MVs at physiologic pH, analyzing hydrolysis ATP, ADP, PP(i) isolated wild-type (WT) as well TNAP-, NPP1- PHOSPHO1-deficient MVs. Comparison catalytic efficiencies identified ATP main substrate hydrolyzed...
Nucleotide pyrophosphatase phosphodiesterase 1 (NPP1) is required for the conversion of extracellular ATP into inorganic pyrophosphate (PPi), a recognised inhibitor hydroxyapatite (HA) crystal formation. A detailed phenotypic assessment mouse model lacking NPP1 (Enpp1−/−) was completed to determine role in skeletal and soft tissue mineralization juvenile adult mice. Histopathological Enpp1−/− mice at 22 weeks age revealed calcification aorta kidney ectopic cartilage formation joints spine....
Abstract 1. This study ascertained how bone of modern meat-type chickens develops under typical commercial conditions and compares development with that in genetic precursor stock. 2. A fast-growing selected strain a slower-growing control were used. Birds weighed weekly. random sample was taken from each population at range ages up to 39 d. 3. tibiotarsus bird X-rayed its dimensions estimated resistance bending determined. Cortical samples ashed measure total mineral, calcium phosphorus...
Human PHOSPHO1 is a phosphatase enzyme for which expression upregulated in mineralizing cells. This has been implicated the generation of Pi matrix mineralization, process central to skeletal development. member haloacid dehalogenase (HAD) superfamily Mg2+-dependent hydrolases. However, substrates are, as yet, unidentified and little known about its activity. We show here that exhibits high specific activities toward phosphoethanolamine (PEA) phosphocholine (PCho). Optimal enzymic activity...
Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events, including myocardial infarction stroke. Previously vascular was thought to be a passive process which involved the deposition calcium phosphate in arteries cardiac valves. However, recent studies have shown that highly regulated, cell-mediated similar bone formation. In this article, we outline current understanding key mechanisms governing highlight...
The development of chondrogenic cell lines has led to major advances in the understanding how chondrocyte differentiation is regulated, and uncovered many signalling pathways gene regulatory mechanisms required maintain normal function. ATDC5 cells are a well established vitro model endochondral ossification; however, current methods limited for mineralisation studies. In this study we demonstrate that culturing presence ascorbic acid 10 mM β-glycerophosphate (βGP) significantly increases...
Patients with end‐stage renal disease (ESRD) have elevated circulating calcium (Ca) and phosphate (Pi), exhibit accelerated progression of calcific aortic valve (CAVD). We hypothesized that matrix vesicles (MVs) initiate the calcification process in CAVD. Ca induced rat interstitial cells (VICs) at 4.5 mM (16.4‐fold; p < 0.05) whereas Pi treatment alone had no effect. (2.7 mM) (2.5 synergistically deposition (10.8‐fold; 0.001) VICs. increased mRNA osteogenic markers Msx2 , Runx2 Alpl (...