A5042294438- Spine and Intervertebral Disc Pathology
- Musculoskeletal pain and rehabilitation
- Osteoarthritis Treatment and Mechanisms
- Pluripotent Stem Cells Research
- Spondyloarthritis Studies and Treatments
- CRISPR and Genetic Engineering
- Pregnancy-related medical research
- Effects of Vibration on Health
- Renal and related cancers
- TGF-β signaling in diseases
- Cervical and Thoracic Myelopathy
- Osteomyelitis and Bone Disorders Research
- Healthcare and Venom Research
- Scoliosis diagnosis and treatment
- NF-κB Signaling Pathways
- Pain Mechanisms and Treatments
- Connective Tissue Growth Factor Research
- Veterinary Orthopedics and Neurology
- Bone Metabolism and Diseases
- Tissue Engineering and Regenerative Medicine
- Adenosine and Purinergic Signaling
- Neurogenetic and Muscular Disorders Research
- Cytokine Signaling Pathways and Interactions
- Bone health and treatments
- Connexins and lens biology
Western University
2016-2025
AO Foundation
2021
University of Pennsylvania
2021
Tokai University
2021
Children’s Health Research Institute
2016
Hospital for Sick Children
2007-2011
Sinai Hospital
2004-2008
University of Toronto
2004-2007
Mount Sinai Hospital
2005
McGill University
2005
This study examines changes in the production of extracellular matrix molecules as well induction tissue degradation vitro formed nucleus pulposus (NP) tissues following incubation with tumor necrosis factor (TNF)alpha.To characterize response NP cells to TNF-alpha, a proinflammatory cytokine present herniated tissues.TNF-alpha is expressed by degenerate intervertebral discs. It implicated pain associated disc herniation, although its role degeneration remains poorly understood.In were...
SUMMARY Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack effective treatment for this widespread problem directly our limited understanding development, maintenance and degeneration. aim study was determine developmental origins nucleus pulposus cells within using novel notochord-specific Cre mouse. To trace fate notochordal disc, we derived mouse line by targeting homeobox gene Noto. Expression...
Abstract Intervertebral disc (IVD) degeneration is the leading cause of disability with no disease-modifying treatment. IVD associated instable mechanical loading in spine, but little known about how stress regulates nucleus notochordal (NC) cells to maintain homeostasis. Here we report that can result excessive integrin α v β 6 -mediated activation transforming growth factor beta (TGFβ), decreased NC cell vacuoles, and increased matrix proteoglycan production, results degenerative disease...
The intervertebral disc is a complex structure responsible for flexibility, multi-axial motion, and load transmission throughout the spine. Importantly, degeneration of thought to be an initiating factor back pain. Due lack understanding pathways that govern degeneration, there are currently no disease-modifying treatments delay or prevent degenerative disease. This review presents overview our current developmental processes regulate formation, with particular emphasis on role notochord...
ABSTRACT A new scoring system based on histo‐morphology of mouse intervertebral disc (IVD) was established to assess changes in different models IVD degeneration and repair. IVDs from strains ages, transgenic mice, or artificially induced were assessed. Morphological features consistently observed normal, early/later stages categorized into a focused nucleus pulposus (NP) annulus fibrosus (AF) changes. “Normal NP” exhibited highly cellularized cell mass that decreased with natural ageing...
Abstract Tumor necrosis factor α (TNFα) inhibits matrix synthesis by chondrocytes in rheumatoid arthritis and osteoarthritis; however, the underlying signaling pathways are poorly characterized. This study investigated TNFα‐activated regulating expression of two key components cartilage matrix—link protein type II collagen. In rat articular chondrocytes, TNFα decreased link collagen mRNA to undetectable levels within 48 h. Levels recovered more readily than following removal cytokine....
Abstract Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory spondyloarthropathy, characterized by ectopic calcification of spinal tissues. Symptoms include spine pain and stiffness, in severe cases dysphagia cord compression. The etiology DISH unknown there are no specific treatments. Recent studies have suggested role for purine metabolism the regulation biomineralization. Equilibrative nucleoside transporter 1 (ENT1) transfers hydrophilic nucleosides, such as adenosine,...
Although it has been observed that aggregate size affects cardiac development, an incomplete understanding of the cellular mechanisms underlying human pluripotent stem cell-derived cardiomyogenesis limited development robust defined-condition cell generation protocols. Our objective was thus to elucidate and molecular endogenous control embryonic (hESC) tissue test hypothesis hESC influences extraembryonic endoderm (ExE) commitment inductive properties. aggregates were generated with 100,...
High-frequency, low-amplitude whole-body vibration (WBV) is being used to treat a range of musculoskeletal disorders; however, there surprisingly limited knowledge regarding its effect(s) on joint tissues. This study was undertaken examine the effects repeated exposure WBV bone and tissues in an vivo mouse model.Ten-week-old male mice were exposed vertical sinusoidal under conditions that mimic those clinically humans (30 minutes per day, 5 days week, at 45 Hz with peak acceleration 0.3g)....
Degenerative disc disease (DDD) is associated with intervertebral degeneration of spinal instability. Here, we report that the cilia nucleus pulposus (NP) cells mediate mechanotransduction to maintain anabolic activity in discs. We found mechanical stress promotes transport parathyroid hormone 1 receptor (PTH1R) and enhances (PTH) signaling NP cells. PTH induces transcription integrin αvβ6 activate transforming growth factor (TGF)-β-connective tissue (CCN2)-matrix proteins cascade....
Mice have been increasingly used as preclinical model to elucidate mechanisms and test therapeutics for treating intervertebral disc degeneration (IDD). Several (IVD) histological scoring systems proposed, but none exists that reliably quantitate mouse pathologies. Here, we report a new robust quantitative IVD histopathological system developed by building consensus from the spine community analyses of previous features noted on different models IDD. The analyzes 14 key nucleus pulposus...
In Brief Study Design. This study describes the formation of nucleus pulposus tissue using a novel engineering approach. Objectives. To determine if construct composed on surface calcium polyphosphate substrate could be formed in vitro with properties similar to native tissue. Summary Background Data. There is no optimal treatment for persistent pain associated intervertebral disc degeneration. Disc replacement artificial discs has met some success, and biologic transplantation limited by...
In Brief Study Design. vitro-formed bovine nucleus pulposus (NP) tissues were used as a model for tumor necrosis factor-α (TNF-α) induced NP degeneration. Objective. To elucidate the signal transduction mechanisms regulating TNF-α matrix metalloproteinase (MMP) activity. Summary of Background Data. is thought to contribute pathophysiology intervertebral disc (IVD) degeneration by up-regulating MMPs, such MMP-2. MMP-2 has been implicated in influencing disease progression and induction...
Objective Currently, our ability to treat intervertebral disc (IVD) degeneration is hampered by an incomplete understanding of development and aging. The specific function matricellular proteins, including CCN2, during these processes remains enigma. aim this study was determine the tissue‐specific localization CCN proteins characterize their role in IVD tissues embryonic age‐related using a mouse model notochord‐specific CCN2 deletion. Methods Expression assessed from wild‐type mice...
Abstract Osteoarthritis (OA) is a multi-factorial disease associated with aging. As the molecular mechanisms underpinning pathogenesis of this are unclear, there no disease-modifying drugs to combat OA. Pannexin 3 (PANX3) has been shown promote cartilage loss during posttraumatic In contrast, ablation Panx3 in male mice results spontaneous full-thickness lesions at 24 mo age. While protected from traumatic intervertebral disc (IVD) degeneration, knockout (KO) show signs IVD altered...