A5083765403- Osteoarthritis Treatment and Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer-related molecular mechanisms research
- Immune Response and Inflammation
- Immune cells in cancer
- MicroRNA in disease regulation
- S100 Proteins and Annexins
- Ion Channels and Receptors
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Musculoskeletal synovial abnormalities and treatments
- Neurogenesis and neuroplasticity mechanisms
- Adenosine and Purinergic Signaling
- Circular RNAs in diseases
- Spine and Intervertebral Disc Pathology
- Intracerebral and Subarachnoid Hemorrhage Research
- Inflammation biomarkers and pathways
- Knee injuries and reconstruction techniques
- Inflammatory mediators and NSAID effects
- Lower Extremity Biomechanics and Pathologies
- Biochemical effects in animals
- Musculoskeletal pain and rehabilitation
- Rheumatoid Arthritis Research and Therapies
- Heat shock proteins research
- Spondyloarthritis Studies and Treatments
University Health Network
2015-2024
Krembil Research Institute
2016-2024
Arthritis Society
2021-2024
Schroeder Arthritis Institute
2021-2024
Toronto Western Hospital
2011-2023
Krembil Foundation
2022
University of Toronto
2006-2016
Western Research Institute
2011
The Scarborough Hospital
2006-2010
Health Net
2009
Microglia respond to CNS injuries and diseases with complex reactions, often called "activation." A pro-inflammatory phenotype (also classical or M1 activation) lies at one extreme of the reactivity spectrum. There were several motivations for this study. First, bacterial endotoxin (lipopolysaccharide, LPS) is most commonly used stimulus microglia, both in vitro vivo; however, cytokines (e.g., IFNγ, TNFα) rather than LPS will be encountered sterile damage disease. We lack direct comparisons...
Microglial cells are highly mobile under many circumstances and, after central nervous system (CNS) damage, they must contend with the dense extracellular matrix (ECM) in order to reach their target sites. In response damage or disease, microglia undergo complex activation processes that can be modulated by environmental cues and culminate either detrimental beneficial outcomes. Thus, there is considerable interest comparing pro-inflammatory ('classical' activation) resolving 'alternative'...
Objective MicroRNA‐34a‐5p (miR‐34a‐5p) expression is elevated in the synovial fluid of patients with late‐stage knee osteoarthritis (OA); however, its exact role and therapeutic potential OA remain to be fully elucidated. This study was undertaken examine miR‐34a‐5p pathogenesis. Methods Expression determined joint tissues human plasma (n = 71). Experiments using mimic or antisense oligonucleotide (ASO) treatment were performed chondrocytes, fibroblast‐like synoviocytes (FLS) 7–9), mouse...
Introduction Recent advances in understanding the biology of ankylosing spondylitis (AS) using innovative genomic and proteomic approaches offer opportunity to address current challenges AS diagnosis management. Altered expression genes, microRNAs (miRNAs) or proteins may contribute immune dysregulation play a significant role onset persistence inflammation AS. The ability exosomes transport miRNAs across cells alter phenotype recipient has implicated perpetuating This study reports first...
Abstract Background Microglia migrate during brain development and after CNS injury, but it is not known how they degrade the extracellular matrix (ECM) to accomplish this. Podosomes are tiny structures with unique ability adhere dissolve ECM. have a two-part architecture: core that rich in F-actin actin-regulatory molecules (for example, Arp2/3), surrounded by ring adhesion structural proteins talin, vinculin). We recently discovered lamellum at leading edge of migrating microglia contains...
MicroRNAs act locally and systemically to impact osteoarthritis (OA) pathophysiology, but comprehensive profiling of the circulating miRNome in early vs late stages OA has yet be conducted. Sequencing emerged as preferred method for microRNA since it offers high sensitivity specificity. Our objective was sequence plasma from 91 patients with [Kellgren-Lawrence (KL) grade 0 or 1 (n = 41)] [KL 3 4 50)] symptomatic radiographic knee identify unique signatures each disease state.MicroRNA...
Spinal cord injury (SCI) triggers inflammatory responses that involve neutrophils, macrophages/microglia and astrocytes molecules potentially cause secondary tissue damage functional impairment. Here, we assessed the contribution of calcium-dependent K + channel KCNN4 (KCa3.1, IK1, SK4) to after moderate contusion lesions in lower thoracic spinal adult mice. Changes mRNA levels (RT-PCR), KCa3.1 protein expression (Western blots), cellular (immunofluorescence) mouse were monitored between 1...
In the hours to days after intracerebral hemorrhage (ICH), there is an inflammatory response within brain characterized by infiltration of peripheral neutrophils and macrophages activation brain-resident microglia astrocytes. Despite strong correlation aging ICH incidence, increasing information about cellular responses, little known temporal- age-related molecular responses ICH. Here, we monitored a panel 27 genes at 6 h 1, 3, 7 was induced injecting collagenase into striatum young adult...
The Ca(2+)-activated K(+) channel, KCa3.1 (KCNN4/IK1/SK4), contributes to "classical," pro-inflammatory activation of microglia, and blockers have improved the outcome in several rodent models CNS damage. For instance, blocking with TRAM-34 rescued retinal ganglion neurons after optic nerve damage vivo and, reduced p38 MAP kinase activation, production reactive oxygen nitrogen species, neurotoxicity by microglia vitro. In pursuing therapeutic potential blockers, it is crucial assess...
Microglia are the “professional” phagocytes of CNS. Phagocytosis is crucial for normal CNS development and maintenance, but it can be either beneficial or detrimental after injury disease. For instance, white matter damage releases myelin debris that must cleared by microglia in order re-myelination to occur. However, phagocytosis also produce damaging reactive oxygen species (ROS). Furthermore, acquire pro-inflammatory (M1) anti-inflammatory (M2) activation states affect cell functions....
Acute CNS damage is commonly studied using rat and mouse models, but increasingly, molecular analysis finding species differences that might affect the ability to translate findings humans. Microglia can undergo complex functional changes, often by in vitro responses discrete activating stimuli. There considerable evidence pro-inflammatory (M1) activation exacerbate tissue damage, while anti-inflammatory (M2) states help resolve inflammation promote repair. However, assessing potential...
The objective of this study is to identify circulating microRNAs that distinguish fast-progressing radiographic knee osteoarthritis (OA) in the Osteoarthritis Initiative cohort by applying microRNA-sequencing.
SC1 is a member of the SPARC family glycoproteins that regulate cell-matrix interactions in developing brain. expressed astrocytes, but nothing known about expression aged or after stroke. We found focal striatal ischemic infarction adult rats, increased astrocytes surrounding infarct and glial scar, was lower at lesion edge. Glial fibrillary acidic protein (GFAP) also increased, it less prominent reactive further from rats. On basis their differential several molecules, 2 types with...
Microglia rapidly respond to CNS injury and disease can assume a spectrum of activation states. While changes in gene expression production inflammatory mediators have been extensively described after classical (LPS-induced) alternative (IL4-induced) microglial activation, less is known about acquired de-activation response IL10. It important understand how states affect their migration invasion; crucial functions the developing CNS. We reported that LPS-treated rat microglia migrate very...
Within hours after stroke, potentially cytotoxic pro-inflammatory mediators are elevated within the brain; thus, one potential therapeutic strategy is to reduce them and skew brain toward an anti-inflammatory state. Because interleukin-4 (IL-4) treatment induces anti-inflammatory, "alternative-activation" state in microglia macrophages vitro, we tested hypothesis that early supplementation of with IL-4 can shift it damage transient focal ischemia. Adult male rat striata were injected...