A5027557364- Osteoarthritis Treatment and Mechanisms
- Genetic and Kidney Cyst Diseases
- Cellular Mechanics and Interactions
- Tendon Structure and Treatment
- Hedgehog Signaling Pathway Studies
- Epigenetics and DNA Methylation
- Cell Adhesion Molecules Research
- Cancer Research and Treatments
- Nanoparticle-Based Drug Delivery
- Cancer Cells and Metastasis
- Proteoglycans and glycosaminoglycans research
- Silk-based biomaterials and applications
- 3D Printing in Biomedical Research
- Genetic Syndromes and Imprinting
- Nanoplatforms for cancer theranostics
- Tissue Engineering and Regenerative Medicine
- Renal and related cancers
- Cell Image Analysis Techniques
- Advanced Fluorescence Microscopy Techniques
- Medical Imaging and Pathology Studies
- Urological Disorders and Treatments
- Fibroblast Growth Factor Research
- Fatty Acid Research and Health
- Bone Metabolism and Diseases
- Bone health and osteoporosis research
Queen Mary University of London
2015-2024
Insigneo
2023
University of Sheffield
2023
Institute for In Vitro Sciences
2021
Predictive Science (United States)
2021
The Francis Crick Institute
2017
University of Manchester
1988-2015
University of London
2001-2012
University of Oxford
2006
Humboldt-Universität zu Berlin
2002
We have profiled, for the first time, an evolving human metastatic microenvironment by measuring gene expression, matrisome proteomics, cytokine and chemokine levels, cellularity, extracellular matrix organization, biomechanical properties, all on same sample. Using biopsies of high-grade serous ovarian cancer metastases that ranged from minimal to extensive disease, we show how nonmalignant cell densities networks evolve with disease progression. Multivariate integration different...
We investigated the role of chondrocyte primary cilium in mechanotransduction events related to cartilage extracellular matrix synthesis. generated conditionally immortalized wild-type (WT) and IFT88orpk (ORPK) mutant chondrocytes that lack cilia assessed intracellular Ca2+ signaling, synthesis, ATP release response physiologically relevant compressive strains a 3-dimensional culture system. All conditions were compared unloaded controls. found required for compression-induced signaling...
The pathways by which chondrocytes of articular cartilage sense their mechanical environment are unclear. Compelling structural evidence suggests that chondrocyte primary cilia mechanosensory organelles. This study used a 3D agarose culture model to examine the effect compressive strain on cilia. Chondrocyte/agarose constructs were subjected cyclic compression (0-15%; 1 Hz) for 0.5-48 h. Additional compressed 48 h and allowed recover 72 in uncompressed free-swelling conditions. Incidence...
Primary cilia are singular, cytoskeletal organelles present in the majority of mammalian cell types where they function as coordinating centres for mechanotransduction, Wnt and hedgehog signalling. The length primary cilium is proposed to modulate function, governed part by activity intraflagellar transport (IFT). In articular cartilage, increased signaling activated osteoarthritis (OA). Here, we examine with exposure quintessential inflammatory cytokine interleukin-1 (IL-1), which...
Primary cilia are cellular appendages important for signal transduction and sensing the environment. Bardet-Biedl syndrome proteins form a complex that is several cytoskeleton-related processes such as ciliogenesis, cell migration division. However, mechanisms by which BBS may regulate cytoskeleton remain unclear. We discovered Bbs4- Bbs6-deficient renal medullary cells display characteristic behaviour comprising poor migration, adhesion division with an inability to lamellipodial filopodial...
Abstract Mechanical loading is essential for the health and homeostasis of articular cartilage, although fundamental mechanotransduction pathways are unclear. Previous studies have demonstrated that cyclic compression up‐regulates proteoglycan synthesis via an intracellular Ca 2+ signalling pathway, mediated by release ATP. However, mechanism(s) ATP has not been elucidated. The present study examines expression putative mechanosensitive ATP‐release channel, connexin 43 whether it expressed...
Abstract The primary cilium regulates cellular signalling including influencing wnt sensitivity by sequestering β-catenin within the ciliary compartment. Topographic regulation of intracellular actin-myosin tension can control stem cell fate which is an important mediator. We hypothesized that topography influences mesenchymal (MSC) signaling through cilia structure and function. MSCs cultured on grooves expressed elongated cilia, reduced actin organization. siRNA inhibition anterograde...
This study adopts a combined computational and experimental approach to determine the mechanical, structural, metabolic properties of isolated chondrocytes cultured within three-dimensional hydrogels. A series linear elastic hyperelastic finite-element models demonstrated that for 24 h in gels which relaxation modulus is <5 kPa exhibit cellular Young's ∼5 kPa. notably greater than reported suspension. The increase cell occurs over 24-h period associated with an organization cortical actin...
Functional recovery after a peripheral nerve injury (PNI) is often poor. There need for therapies that protect neurons against and enhance regeneration. Omega-3 polyunsaturated fatty acids (PUFAs) have been shown to therapeutic potential in variety of neurological disorders, including acute traumatic injury. The objective this study was assess the neuroprotective pro-regenerative ω-3 PUFAs PNI. We investigated mice express fat-1 gene encoding acid desaturase, which leads an increase...
Mechanical characterisation of soft biological tissues using standard compression or tensile testing presents a significant challenge due to specimen geometrical irregularities, difficulties in cutting intact and appropriately sized test samples, issues with slippage damage at the grips. Indentation can overcome these problems but requires fitting model resulting load–displacement data order calculate moduli. Despite widespread use this technique, few studies experimentally validate their...
Abstract Primary cilia are single non-motile organelles that provide a highly regulated compartment into which specific proteins trafficked as critical part of various signaling pathways. The absence primary has been shown to prevent differentiation human mesenchymal stem cells (hMSCs). Changes in length crucial for regulating events; however it is not known how alterations structure relate differentiation. This study tested the hypothesis changes required cell hMSCs expressed were labeled...
ObjectivePhysiological mechanical loading reduces inflammatory signalling in numerous cell types including articular chondrocytes however the mechanism responsible remains unclear. This study investigates role of chondrocyte primary cilia and associated intraflagellar transport (IFT) regulation interleukin-1β (IL-1β) signalling.DesignIsolated cartilage explants were subjected to cyclic presence absence cytokine IL-1β. Nitric oxide (NO) prostaglandin E2 (PGE2) release used monitor IL-1β...
ObjectiveCartilage health is maintained in response to a range of mechanical stimuli including compressive, shear and tensile strains associated alterations osmolality. The osmotic-sensitive ion channel Transient Receptor Potential Vanilloid 4 (TRPV4) required for mechanotransduction. Mechanical inhibit interleukin-1β (IL-1β) mediated inflammatory signalling, however the mechanism unclear. This study aims clarify role TRPV4 this response.DesignTRPV4 activity was modulated glycogen synthase...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense and stiff extracellular matrix (ECM) associated with tumor progression therapy resistance. To further the understanding of how stiffening microenvironment (TME) contributes to aggressiveness, three‐dimensional (3D) self‐assembling hydrogel disease model developed based on peptide amphiphiles (PAs, PA‐E3Y ) designed tailor stiffness. The displays nanofibrous architectures reminiscent native TME enables study invasive...
Isolated chondrocytes stained with fluo 4-AM and visualized using standard confocal microscopy techniques exhibited Ca2- transients oscillations. Decreasing the power of laser light decreased percent-age cells exhibiting these Ca2+ signals. Treatment antioxidant ascorbate reduced response, suggesting that it was mediated by light-induced release reactive oxygen species (ROS). Cell viability 24 h after 1-h imaging period approximately 90% for were neither fluorescently nor subjected to...
Ca 2+ signaling forms part of a possible mechanotransduction pathway by which chondrocytes may alter their metabolism in response to mechanical loading. In this study, well-characterized model system utilizing bovine articular embedded 4% agarose constructs was used investigate the effect physiological compressive strain applied after 1 and 3 days culture. The intracellular concentration measured use ratiometric indicator indo 1-AM confocal microscopy. A positive defined as percent increase...