A5067359842- Osteoarthritis Treatment and Mechanisms
- Pain Mechanisms and Treatments
- Inflammatory mediators and NSAID effects
- Rheumatoid Arthritis Research and Therapies
- Knee injuries and reconstruction techniques
- Cell Adhesion Molecules Research
- Neuropeptides and Animal Physiology
- Protease and Inhibitor Mechanisms
- Chemokine receptors and signaling
- Exercise and Physiological Responses
- Monoclonal and Polyclonal Antibodies Research
- Proteoglycans and glycosaminoglycans research
- Total Knee Arthroplasty Outcomes
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Cytokine Signaling Pathways and Interactions
- Pharmacological Effects and Assays
- Ion channel regulation and function
- Peptidase Inhibition and Analysis
- Musculoskeletal pain and rehabilitation
- Immune Response and Inflammation
- Systemic Lupus Erythematosus Research
- Chemical Synthesis and Analysis
- HER2/EGFR in Cancer Research
- Connective tissue disorders research
- Tendon Structure and Treatment
Rush University Medical Center
2016-2025
Chicago Anesthesia Pain Specialists
2024
Rush University
2015-2024
Ghent University Hospital
1989-2022
American College of Rheumatology
2018-2021
Yale University
2017-2020
AID Atlanta
2020
Women's Hospital
2020
Center for Rheumatology
2012-2017
Lund University
2017
The therapeutic potential of cannabidiol (CBD), the major nonpsychoactive component cannabis, was explored in murine collagen-induced arthritis (CIA). CIA elicited by immunizing DBA/1 mice with type II collagen (CII) complete Freund's adjuvant. CII used either bovine or murine, resulting classical acute chronic relapsing CIA, respectively. CBD administered after onset clinical symptoms, and both models treatment effectively blocked progression arthritis. equally effective when i.p. orally....
Abstract Objective Recent published studies have shown that cartilage from ADAMTS‐5–knockout mice, but not ADAMTS‐4– or ADAMTS‐1–knockout is significantly protected degradation. The present study was undertaken to evaluate the respective roles of these enzymes in human breakdown, using a small interfering RNA (siRNA) approach assess effects inhibition each enzyme normal and osteoarthritic (OA) explants. Methods activities siRNA specifically targeting ADAMTS‐1, ‐4, ‐5 were assessed by...
Osteoarthritis is one of the leading causes chronic pain, but almost nothing known about mechanisms and molecules that mediate osteoarthritis-associated joint pain. Consequently, treatment options remain inadequate replacement often inevitable. Here, we use a surgical mouse model captures long-term progression knee osteoarthritis to longitudinally assess pain-related behaviors concomitant changes in innervating dorsal root ganglia (DRG). We demonstrate monocyte chemoattractant protein...
Non-opioid targets are needed for addressing osteoarthritis pain, which is mechanical in nature and associated with daily activities such as walking climbing stairs. Piezo2 has been implicated the development of but mechanisms by this occurs remain poorly understood, including role nociceptors. Here we show that nociceptor-specific conditional knock-out mice were protected from sensitization inflammatory joint pain female mice, male well both knee swelling repeated intra-articular injection...
It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal scores patients do not correlate with synovial inflammation. We developed a machine-learning approach (graph-based gene expression module identification or GbGMI) identify an 815-gene associated biopsy samples from established RA who had limited at arthroplasty. then validated this finding independent cohort of early untreated little Single-cell RNA...
Osteoarthritis is a degenerative joint disorder characterized by breakdown of articular cartilage. Degradation aggrecan, which together with type II collagen provides cartilage its unique characteristics compressibility and elasticity, an early sustained feature osteoarthritis. The present work was set up to identify the enzyme(s) responsible for aggrecan in We found that two aggrecanases, ADAM-TS4 ADAM-TS5, are osteoarthritic they degradation without participation matrix metalloproteinases....
ObjectiveThe role of inflammation in structural and symptomatic osteoarthritis (OA) remains unclear. One key mediator is the chemokine CCL2, primarily responsible for attracting monocytes to sites injury. We investigated CCL2 its receptor CCR2 experimental OA.DesignOA was induced 10 weeks old male wild type (WT), Ccl2−/− Ccr2−/− mice, by destabilisation medial meniscus (DMM). RNA extracted from whole joints at 6 h 7 days post-surgery examined reverse transcription polymerase chain reaction...
Objective/MethodAggrecanase activity, most notably ADAMTS-5, is implicated in pathogenic cartilage degradation. Selective monoclonal antibodies (mAbs) to both ADAMTS-5 and ADAMTS-4 were generated vitro, ex vivo systems utilized assess target engagement, aggrecanase inhibition modulation of disease-related endpoints with the intent selecting a candidate for clinical development osteoarthritis (OA).ResultsStructural mapping predicts potent mAbs employ unique mode by cross-linking catalytic...
To determine whether selected damage-associated molecular patterns (DAMPs) present in the osteoarthritic (OA) joints of mice excite nociceptors through Toll-like receptor 4 (TLR-4).The ability S100A8 and α2 -macroglobulin to was determined by measuring release monocyte chemoattractant protein 1 (MCP-1) cultured dorsal root ganglion (DRG) cells as well intracellular calcium concentration ([Ca(2+) ]i ) DRG neurons from naive or that had undergone surgical destabilization medial meniscus (DMM)...
Pain is the predominant symptom of osteoarthritis, but connection between joint damage and genesis pain not well understood. Loss articular cartilage a hallmark it occurs through enzymatic degradation aggrecan by cleavage mediated disintegrin metalloproteinase with thrombospondin motif 4 (ADAMTS-4) or ADAMTS-5 in interglobular domain (E373–374A). Further MMPs (N341–342F) releases 32-amino-acid fragment (32-mer). We investigated role this 32-mer driving pain. found that excites dorsal root...
Osteoarthritis (OA) is a leading cause of chronic pain, yet OA pain management remains poor. Age the strongest predictor development, and mechanisms driving are unclear. We undertook this study to characterize age-associated changes in knee OA, pain-related behaviors, dorsal root ganglion (DRG) molecular phenotypes mice both sexes.
Knee joints are densely innervated by nociceptors. In human knees and rodent models, sprouting of nociceptors has been reported in late-stage osteoarthritis (OA). Here, we sought to describe progressive nociceptor remodeling early OA, using four distinct experimental mouse models.