A5073187518- Bone health and osteoporosis research
- Bone Metabolism and Diseases
- Bone health and treatments
- Bone fractures and treatments
- Osteoarthritis Treatment and Mechanisms
- Veterinary Medicine and Surgery
- Veterinary Oncology Research
- Estrogen and related hormone effects
- Cellular Mechanics and Interactions
- Urological Disorders and Treatments
- Connective tissue disorders research
- Veterinary Orthopedics and Neurology
- Muscle Physiology and Disorders
- Orthopedic Surgery and Rehabilitation
- Signaling Pathways in Disease
- Pediatric Urology and Nephrology Studies
- Orthopaedic implants and arthroplasty
- Trauma Management and Diagnosis
- Shoulder Injury and Treatment
- Pediatric Hepatobiliary Diseases and Treatments
- Organ Transplantation Techniques and Outcomes
- Veterinary Equine Medical Research
- Veterinary Pharmacology and Anesthesia
- Wnt/β-catenin signaling in development and cancer
- Lysosomal Storage Disorders Research
University of Bristol
2014-2025
At Bristol
2012-2024
The Langton Grammar School for Boys
2020-2021
Ashwini Hospital
2014
Royal Veterinary College
2011-2013
University of London
2011-2013
Abstract There is a widely held view that the relationship between mechanical loading history and adult bone mass/strength includes an adapted state or “lazy zone” where remains constant over wide range of strain magnitudes. Evidence to support this theory circumstantial. We investigated possibility artifact that, across normal experience, features architecture associated with strength are linearly related in size their experience. Skeletally mature female C57BL/6 mice were right sciatic...
ABSTRACT Bones adjust their mass and architecture to be sufficiently robust withstand functional loading by adapting strain environment. This mechanism appears less effective with age, resulting in low bone mass. In male female young adult (17-week-old) old (19-month-old) mice, we investigated the effect of age vivo on bones' adaptive response vitro primary cultures osteoblast-like cells derived from cortices. Right tibias were axially loaded alternate days for 2 weeks. Left non-loaded...
Abstract Estrogen receptor-α (ERα) is crucial for the adaptive response of bone to loading but role endogenous estradiol (E2) this unclear. To determine in vivo ligand dependency and relative roles different ERα domains osteogenic mechanical loading, gene-targeted mouse models with (1) a complete inactivation (ERα−/−), (2) specific activation function 1 (AF-1) (ERαAF-10), or (3) ERαAF-2 (ERαAF-20) were subjected axial tibia, presence absence (ovariectomy [ovx]) E2. Loading increased cortical...
Sclerostin is a potent inhibitor of bone formation which down‐regulated by mechanical loading. To investigate the mechanisms involved we subjected Saos2 human osteoblastic cells to short periods dynamic strain and used quantitative reverse transcriptase polymerase chain reaction compare their responses unstrained controls. Strain‐induced Sost down‐regulation was recapitulated cyclo‐oxygenase‐2‐mediated PGE2, acting through EP4 receptor, whereas strain‐related up‐regulation osteocalcin...
Age-related degenerative changes within the vertebral column are a significant cause of morbidity with considerable socio-economic impact worldwide. An improved understanding these through development experimental models may lead to improvements in existing clinical treatment options. The zebrafish is well-established model for study skeletogenesis potential gerontological research. With advancing age, frequently develop gross deformities their column, previously ascribed reduced trunk...
To determine the effect of estrogen receptors (ER) α and β on bones' adaptive response to loading, we subjected right tibiae mice lacking ERα or ERβ activity either axial loading disuse. Adaptive changes in architecture were assessed by comparing differences between (treated) left (control) these genotypes as microcomputed tomography. In female ERα−/− mice, net-osteogenic was lower cortical bone compared with their wild-type littermates (11.2 vs. 20.9% ERα+/+), but it higher both cancellous...
Experiments to investigate bone's physiological adaptation mechanical loading frequently employ models that apply dynamic loads bones in vivo and assess the changes mass architecture result. It is axiomatic will only show an adaptive response if applied artificial environment differs a significant way from which have been habituated by normal functional loading. generally assumed this similar between experimental groups. In study reported here we found was not always case. Male female...
In old animals, bone's ability to adapt its mass and architecture functional load-bearing requirements is diminished, resulting in bone loss characteristic of osteoporosis. Here we investigate transcriptomic changes associated with this impaired adaptive response. Young adult (19-week-old) aged (19-month-old) female mice were subjected unilateral axial tibial loading their cortical shells harvested for microarray analysis between 1 h 24 following (36 per age group, 6 group at time points)....
Abstract OBJECTIVE The aim of this study was to report the outcome and prognosis canine patients treated medically or surgically for rectal plasmacytomas identify factors associated with recurrence, mortality, progression multiple myeloma. METHODS databases 7 referral hospitals were reviewed. Kaplan-Meier method Cox proportional hazards analysis used determine association a range variables recurrence progression-free interval patients. RESULTS 20 dogs included. Nineteen cases surgically, 1...
To establish whether the combination of anti-resorptive therapy with mechanical loading has a negative, additive or synergistic effect on bone structure, we assessed separate and combined effects risedronate non-invasive dynamic trabecular cortical bone. Seventeen-week-old female C57BL/6 mice were given daily subcutaneous injections vehicle (n=20) at dose 0.15, 1.5, 15 150 μg/kg/day (n=10 in each) for 17 days. From fourth day treatment, right tibiae subjected to single period axial (40...
Investigations into the effect of (re)modeling stimuli on cortical bone in rodents normally rely analysis changes mass and architecture at a narrow cross-sectional site. However, it is well established that effects axial loading produce site-specific throughout bones' structure. Non-mechanical influences (e.g., hormones) can be additional to or oppose locally controlled adaptive responses may have more generalized effects. Tools currently available study adaptation are limited. Here, we...
Genome Wide Association Studies suggest that Wnt16 is an important contributor to the mechanisms controlling bone mineral density, cortical thickness, strength and ultimately fracture risk. acts on osteoblasts osteoclasts and, in bone, predominantly derived from osteoblasts. This led us hypothesize low mass would be associated with levels of expression increased by anabolic factors, including mechanical loading. We therefore investigated context ageing, loading unloading, estrogen deficiency...
Decreased effectiveness of bones' adaptive response to mechanical loading contributes age-related bone loss. In young mice, intermittent administration parathyroid hormone (iPTH) at 20-80μg/kg/day interacts synergistically with artificially applied increase mass. Here we report investigations on the effect different doses and duration iPTH treatment mice whose osteogenic artificial is impaired by age. One group aged, 19-month-old female C57BL/6 was given 0, 25, 50 or 100μg/kg/day for 4weeks....
Mechanical loading-related strains trigger bone formation by osteoblasts while suppressing resorption osteoclasts, uncoupling the processes of and resorption. Osteocytes may orchestrate this process in part secreting sclerostin (SOST), which inhibits osteoblasts, expressing receptor activator nuclear factor-κB ligand (RANKL/TNFSF11) recruits osteoclasts. Both SOST RANKL are targets master osteoblastic transcription factor RUNX2. Subjecting human Saos-2 cells to strain four point bending...
Protein kinase-like endoplasmic reticulum kinase (PERK) and protein R (PKR) are implicated in stress-induced arthritis pro-inflammatory cytokine-mediated cartilage degradation vitro, respectively. We determined whether knockout of the cellular inhibitor PERK PKR, P58(IPK) causes joint degeneration vivo these molecules activated human osteoarthritis (OA).Sections knee joints from P58(IPK)-null wild-type mice aged 12-13 23-25 months were stained with toluidine blue scored for using research...
To compare the outcomes of dogs treated at a single institution for extrahepatic congenital portosystemic shunts (CPSS) by thin film banding (TFB) or placement an ameroid constrictor (AC).Retrospective case series.Seventy-six client-owned with CPSS TFB (n = 53) AC 23).Records were reviewed signalment, preoperative, intraoperative, and postoperative management short-term outcomes. Data on second surgeries reviewed. Long-term obtained via owner-directed health-related quality life...
ABSTRACT Exposure of bone to dynamic strain increases the rate division osteoblasts and also influences directional organization cellular molecular structure tissue that they produce. Here, we report brief exposure substrate (sufficient rapidly stimulate cell division) orientation osteoblastic division. The initial proliferative response involves canonical Wnt signaling can be blocked by sclerostin. However, strain-related is independently influenced through noncanonical Wnt/planar polarity...
We aimed to determine whether aged bone's diminished response mechanical loading could be rescued by modulating habitual activity. By reducing background loading, increased a level no different young mice. This suggests, given the right stimulus, that ageing bone can respond loading. Age-related decline in mass has been suggested represent an impaired ability of adapt its environment. In mice, tibia's external shown increase when activity is reduced sciatic neurectomy. Here we investigate if...
Objective To determine whether use of colored indicator gloves affects perforation detection rate and to identify risk factors for glove during veterinary orthopedic surgery. Study Design Prospective randomized controlled trial. Sample Population 574 double pairs worn 300 surgical procedures (2,296 gloves). Methods Primary assistant surgeons double‐gloved all procedures. Type inner (standard or indicator) was the first 360 by 180 Perforations detected were recorded changed if requested. For...