A5026190605- Knee injuries and reconstruction techniques
- Osteoarthritis Treatment and Mechanisms
- Total Knee Arthroplasty Outcomes
- Tendon Structure and Treatment
- Exercise and Physiological Responses
- Lower Extremity Biomechanics and Pathologies
- Ion Channels and Receptors
- Ion channel regulation and function
- Heat shock proteins research
- Erythrocyte Function and Pathophysiology
- Sports injuries and prevention
- Blood properties and coagulation
- Cellular Mechanics and Interactions
- Inflammatory mediators and NSAID effects
- Bone Tissue Engineering Materials
- Periodontal Regeneration and Treatments
- Shoulder Injury and Treatment
- Veterinary Equine Medical Research
- Vitamin C and Antioxidants Research
- Wastewater Treatment and Reuse
- Polymer Surface Interaction Studies
- Hemophilia Treatment and Research
- Advanced Neuroimaging Techniques and Applications
- Orthopedic Surgery and Rehabilitation
- Health and Medical Research Impacts
Duke University
2015-2024
Duke Medical Center
2005-2017
Duke University Hospital
2005-2016
Significance Cartilage, a mechanically sensitive tissue that covers joints, is essential for vertebrate locomotion by sustaining skeletal mobility. Transduction of mechanical stimuli cartilage cells, chondrocytes, leads to biochemical–metabolic responses. Such mechanotransduction can be beneficial maintenance when evoked low-level stimuli, or have health-adverse effects via cartilage-damaging high-strain stress. Thus, mechanotrauma relevant the pathogenesis osteoarthritis. Molecular...
Significance Osteoarthritis is a global health problem that affects load-bearing joints, causing loss of mobility and enormous healthcare costs. However, disease-modifying approaches are lacking. Here, we report cellular mechanism inflammatory signaling in chondrocytes, the component cartilage. We show how osteoarthritis-relevant levels interleukin-1α reprogram articular chondrocytes so they become more susceptible to mechanical trauma, which sense via Piezo1/2-mechanosensitive ion channels....
ABSTRACT Cartilage degeneration with osteoarthritis (OA) is believed to involve the activities of interleukin‐1 (IL‐1), which exists as alpha and beta isoforms. The goal this study was measure concentrations both isoforms IL‐1 in synovial fluid normal spontaneously osteoarthritic porcine knees, test hypothesis that physiologic IL‐1α IL‐1β exhibit different potencies activating calcium signaling, production matrix metalloproteinases nitric oxide, loss proteoglycans tissue mechanical...
Abstract Osteoarthritis (OA) is a progressive degenerative disease of articular cartilage and surrounding tissues, associated with both advanced age joint injury. Biomechanical factors play critical role in the onset progression OA, yet mechanisms through which physiologic or pathologic mechanical signals are transduced into cellular response not well understood. Defining mechanosensory pathways during OA pathogenesis may yield novel strategies targets for treatment OA. The transient...
Temporomandibular joint disorder (TMJD) is known for its mastication-associated pain. TMJD medically relevant because of prevalence, severity, chronicity, the therapy-refractoriness pain, and largely elusive pathogenesis. Against this background, we sought to investigate pathogenetic contributions calcium-permeable TRPV4 ion channel, robustly expressed in trigeminal ganglion sensory neurons, TMJ inflammation pain behavior. We demonstrate here that critical TMJ-inflammation-evoked behavior...
Mechanobiologic signals regulate cellular responses under physiologic and pathologic conditions. Using synthetic biology tissue engineering, we developed a mechanically responsive bioartificial that responds to mechanical loading produce preprogrammed therapeutic biologic drug. By deconstructing the signaling networks induced by activation of sensitive ion channel transient receptor potential vanilloid 4 (TRPV4), created TRPV4-responsive genetic circuits in chondrocytes. We engineered these...
Abstract Objective To examine the hypotheses that increasing concentrations of interleukin‐1 (IL‐1) or tumor necrosis factor α (TNFα) inhibit integrative repair knee meniscus in an vitro model system, and inhibitors these cytokines will enhance repair. Methods Explants (8 mm diameter) were harvested from porcine medial menisci. simulate a full‐thickness defect, 4‐mm–diameter core was removed reinserted. cultured for 14, 28, 42 days presence 0–1,000 pg/ml IL‐1 TNFα. also TNFα with receptor...
Abstract Damage or loss of the meniscus is associated with progressive osteoarthritic degeneration knee joint. Injured and degenerative joints are characterized by elevated levels pro‐inflammatory cytokine interleukin‐1 (IL‐1), which prolonged exposure can induce catabolic anti‐anabolic activities that inhibit tissue repair. We used an in vitro model system to examine hypotheses acute IL‐1 inhibits meniscal repair, IL‐1–mediated increase matrix metalloproteinase (MMP) activity inhibition...
Damage or injury of the meniscus is associated with onset and progression knee osteoarthritis (OA). The intrinsic repair capacity inhibited by inflammatory cytokines, such as interleukin-1 (IL-1). Using an in vitro meniscal model system, we examined hypothesis that inhibition matrix metalloproteinases (MMPs) presence IL-1 will enhance lesions. Integrative was between two concentric explants cultured various MMP inhibitors for 14 days. Throughout culture period, assessed total specific...
Obesity is one of the primary risk factors for osteoarthritis. Increased adiposity associated not only with alterations in joint loading, but also increased systemic and concentrations adipose tissue-derived cytokines, or "adipokines," that promote a state chronic, low-grade inflammation may act concert other cytokines to increase degeneration. However, direct effect adipokines, such as leptin, visfatin, interleukin-6 (IL-6), on tissues, articular cartilage meniscus, are fully understood. In...
Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) are up-regulated in injured osteoarthritic knee joints. IL-1 TNF-α inhibit integrative meniscal repair; however, the mechanisms by which this inhibition occurs not fully understood. Transforming growth factor-β1 (TGF-β1) increases cell proliferation accumulation, enhances repair. An improved understanding of modulating migration will help to improve approaches for enhancing intrinsic or tissue-engineered repair meniscus. The goal study...
Purpose: Meniscus tears are a common knee injury and associated with the development of post-traumatic osteoarthritis (OA). The purpose this study is to evaluate potential OA mediators in synovial fluid serum meniscus tear subjects compared those radiographic non-OA control knees. Materials methods: Sixteen an isolated unilateral six who served as reference controls (knee Kellgren-Lawrence grade 0-1) were recruited. Twenty-one biomarkers measured from both groups. further stratified by type...
While the prevalence of osteoporosis is growing rapidly with population aging, therapeutic options remain limited. Here, we identify potentially novel roles for CaV1.2 L-type voltage-gated Ca2+ channels in osteogenesis and exploit a transgenic gain-of-function mutant to stem bone loss ovariectomized female mice. We show that endogenous expressed developing within proliferating chondrocytes osteoblasts. Using primary BM stromal cell (BMSC) cultures, found influx through activates osteogenic...
Abstract Background Anterior cruciate ligament (ACL) and meniscus tears are common knee injuries. Despite the high rate of post-traumatic osteoarthritis (PTOA) following these injuries, contributing factors remain unclear. In this study, we characterized immune cell profiles normal injured joints at time ACL meniscal surgeries. Methods Twenty-nine patients (14 meniscus-injured 15 ACL-injured) undergoing and/or surgery but with a contralateral were recruited. During surgery, synovial fluid...
Abstract Objective To evaluate the dehydroascorbate (DHA) transport mechanisms in human chondrocytes. Methods The of L‐ 14 C‐DHA chondrocytes was analyzed under various conditions, including use RNA interference (RNAi), to determine role glucose transporter 1 (GLUT‐1) and GLUT‐3 effects physiologically relevant oxygen tensions on transport. In order estimate contributions reduced ascorbic acid (AA) DHA intracellular (Asc), quantities AA were measured synovial fluid samples from...
Current therapies for meniscal injury seek to preserve and repair damaged tissue since loss of is associated with degenerative changes in the joint, ultimately leading osteoarthritis (OA). After a tear, difficulty i