Abstract MicroRNA (miRNA) has the potential for cross-regulation and functional integration of discrete biological processes during complex physiological events. Utilizing common human condition tendinopathy as a model system to explore immediate inflammation matrix synthesis by miRNA we observed that elevated IL-33 expression is characteristic early tendinopathy. Using in vitro tenocyte cultures vivo models tendon damage, demonstrate such plays pivotal role transition from type 1 3 collagen...

Tendon disorders represent the most common musculoskeletal complaint for which patients seek medical attention; inflammation drives tendon degeneration before tearing and impairs healing after repair. Clinical evidence has implicated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway as a correlate pain-free return to function surgical However, it is currently unknown whether this response reaction or driver pathology. Therefore, we aimed understand clinically...

Abstract Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy. We sought evidence interleukin 17A (IL-17A) expression in early human tendinopathy thereafter, explored mechanisms whereby IL-17A mediated inflammation tissue remodeling tenocytes. Torn supraspinatus tendon (established pathology) matched intact subscapularis (representing ‘early pathology’) along with control biopsies were collected from patients undergoing shoulder surgery....

Introduction Frozen shoulder is a common, fibro-proliferative disease characterised by the insidious onset of pain and progressively restricted range movement. Despite prevalence this disease, there limited understanding molecular mechanisms underpinning pathogenesis debilitating disease. Previous studies have identified increased myofibroblast differentiation proliferation, immune cell influx dysregulated cytokine production. We hypothesised that subpopulations within fibroblast compartment...

Cobalt-chromium (Co-Cr) alloy metal-on-metal hip resurfacing is increasingly common among younger more active patients suffering from osteoarthritis. Recent reports have increased awareness of metal ions leaching metallic articulations; this ion exposure may adverse effects on the immune system. As previous studies reported alterations in lymphocyte number and function with Co-Cr implants, we investigated clinically relevant concentrations Cr(6+) Co(2+) primary human lymphocytes vitro. Here,...

Abstract Alarmins S100A8 and S100A9 are endogenous molecules released in response to environmental triggers cellular damage. They constitutively expressed immune cells such as monocytes neutrophils their expression is upregulated under inflammatory conditions. The molecular mechanisms that regulate pathways tendinopathy largely unknown therefore identifying early effectors essential understanding the pathology. Based on our previous investigations highlighting an alarmin mediated pathology...

Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as intra-articular injection or wash being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage these can be harmful the patient. This study investigated effects of TXA on human periarticular primary cell cultures using clinically relevant concentrations.Tendon, synovium, cartilage obtained from routine...

Objectives Increasing evidence suggests that inflammatory mechanisms play a key role in chronic tendon disease. After observing T cell signatures human tendinopathy, we explored the interaction between cells and stromal or tenocytes to define their functional contribution tissue remodelling inflammation amplification hence disease perpetuation. Methods were quantified characterised healthy tendinopathic tissues by flow cytometry (FACS), imaging mass (IMC) single RNA-seq. Tenocyte activation...

Tendon injuries (tendinopathies) are common in human and equine athletes characterized by dysregulated collagen matrix, resulting tendon damage. We have previously demonstrated a functional role for microRNA29a (miR29a) as post-transcriptional regulator of 3 expression murine injury. Given the translational potential, we designed randomized, blinded trial to evaluate potential miR29a replacement therapy therapeutic option treat tendinopathy an model that closely mimics disease. injury was...

The pathophysiological mechanisms behind proliferation of fibroblasts and deposition dense collagen matrix in idiopathic frozen shoulder remain unclear. Alarmins (also known as danger signals) are endogenous molecules that released into the extracellular milieu after infection or tissue injury signal cell damage.To investigate whether presence alarmins is higher patients with than control subjects.Controlled laboratory study.Shoulder capsule samples were collected from 10 unstable shoulders...

Significance Frozen shoulder (FS) is a classic example of prevalent debilitating pathological inflammatory fibrosis. Using approaches to dissect the molecular pathways subserving FS, we demonstrate immune cell landscape in FS shifts from primarily macrophages T cells disease. We find tissue are able secrete cytokine IL-17A, and fibroblasts have greater expression receptor IL-17RA. Thus, produce fibrotic responses following IL-17A stimulation, which can be abrogated NF-κB pathway inhibition...

SUMMARY Tendinopathy is a tendon disorder that caused by the failure to self-repair and has many pathological characteristics such as disorganized ECM decreased cell viability. We have identified possible target combat these changes, AMPK, an energy stress sensor was shown maintain intracellular homeostasis. Through bulk RNA-sequencing of healthy tendinopathic tendons from humans we novel finding downregulation AMPK signaling in samples which suggests plays role Our studies utilizing...

Objectives Tendinopathy is a frequent clinical problem and represents an extraordinary health economic socioeconomic burden with high unmet medical needs. Recent evidence suggests blockade of interleukin 17A (IL-17A) for tendinopathy therapy. The present preclinical study elucidates the biological mechanisms IL-17A pathway stimulation in tendinopathy. Methods We explored whether other IL-17 family members are differentially expressed biopsies healthy, early-stage late-stage tendinopathic...

// Michela Colombo 1 , Katja Thümmler 2 Leonardo Mirandola Silvia Garavelli Katia Todoerti 6 Luana Apicella Elisa Lazzari Marialuigia Lancellotti Natalia Platonova Moeed Akbar Maurizio Chiriva-Internati 4 Richard Soutar 5 Antonino Neri 3 Carl S. Goodyear and Raffaella Chiaramonte Department of Health Sciences, Università degli Studi di Milano, Italy Institute Infection, Immunity Inflammation, College Medical, Veterinary Life University Glasgow, UK Clinical Sciences Community Health, Milano;...

Objectives To seek evidence of the danger molecule, high-mobility group protein B1 (HMGB1) expression in human tendinopathy and thereafter, to explore mechanisms where HMGB1 may regulate inflammatory mediators matrix regulation tendinopathy. Methods Torn supraspinatus tendon (established pathology) matched intact subscapularis (representing ‘early pathology’) biopsies were collected from patients undergoing arthroscopic shoulder surgery. Control samples stabilisation Markers inflammation...

This study used a rodent air-pouch model to assess the acute inflammatory response cobalt–chromium (CoCr) alloy wear debris from metal-on-metal hip resurfacing implant that may contribute joint failure. Air-pouches were injected with either sterile phosphate-buffered saline, 1 μg lipopolysaccharide (LPS) or 2.5 mg CoCr debris. The in situ was monitored 4, 24, 48 and 72 h 7 days later. A flow cytometric analysis of exudates showed induced different pattern compared LPS. LPS strong early (4 h)...

Abstract Metal‐on‐metal hip replacement implants generate wear debris and release ions both locally systemically in patients. To investigate dissemination of metal, we determined blood organ levels cobalt (Co), chromium (Cr), molybdenum (Mo) following the implantation Co–Cr alloy mice using skin pouches as a model system. We observed increased metal for up to 72 h; Co were highest remained elevated 7 days. all organs studied (liver, kidney, spleen, lung, heart, brain, testes), with peak at...

Fibrotic disorders represent common complex disease pathologies that are therapeutically challenging. Inflammation is associated with numerous fibrotic pathogeneses; however, its role in the multifaceted mechanisms of fibrosis remains unclear. IL-13 implicated aberrant responses involved disease, and we aimed to understand inflammatory processes a disorder, Dupuytren's disease. We demonstrated T-cells produced IFN-g, which induced secretion from mast cells up-regulated IL-13Ra1 on...

Rotator cuff repair is usually successful, but retear not uncommon. It has been previously identified that there a higher incidence of apoptosis in the edges torn supraspinatus tendon. A prospective cohort study was conducted with 28 patients-14 rotator tear patients, 5 instability and 9 Anterior cruciate ligament reconstruction patients to determine whether any increase several genes implicated apoptosis, including Fas receptor (FasR), ligand, Aifm-1, Bcl-2, Fadd, Bax, caspase-3. There...

Background: The use of the vancomycin wrap to pretreat hamstring graft in anterior cruciate ligament reconstruction (ACLR) has grown popularity since it was first described 2012 and significantly reduced rates postoperative infection. However, remains unknown if this antibiotic treatment affects molecular composition graft. Purpose: To establish whether with at 5 mg/mL, most commonly used concentration, alters function ACLR. Study Design: Controlled laboratory study. Methods: Surplus tendon...

To assess the involvement of CCR6/CCL20 axis in psoriatic arthritis (PsA) and psoriasis (PsO) to evaluate its potential as a therapeutic target.First, we quantified CCL20 levels peripheral blood synovial fluid from PsA patients examined presence CCR6+ cells tendon tissue. Utilizing an interleukin-23 minicircle DNA (IL-23 MC) mouse model exhibiting key features both PsO PsA, investigated CCR6 expression well preventive effect blockade. Healthy stromal were stimulated vitro with IL-1β...

Abstract The expression of chemokines and chemokine receptors was studied in Leishmania donovani (LD)‐infected human mononuclear phagocytes the monocytic cell line THP1. Our studies showed that LD infection caused upregulation three β (macrophage inflammatory protein‐1 alpha (MIP‐1α), MIP‐1β RANTES (regulated on activation normal T expressed secreted)), one α (interleukin‐8 (IL‐8)) CC receptor 5 (CCR5) but not CCR1, as evident from reverse transcriptase‐polymerase chain reaction (RT‐PCR)...