A5016276875- Tendon Structure and Treatment
- Shoulder Injury and Treatment
- Veterinary Equine Medical Research
- Sports injuries and prevention
- Rheumatoid Arthritis Research and Therapies
- Osteoarthritis Treatment and Mechanisms
- Exercise and Physiological Responses
- Bee Products Chemical Analysis
- Shoulder and Clavicle Injuries
- Myofascial pain diagnosis and treatment
- Streptococcal Infections and Treatments
- Immune cells in cancer
- Cytokine Signaling Pathways and Interactions
- Inflammatory mediators and NSAID effects
- Musculoskeletal synovial abnormalities and treatments
- Knee injuries and reconstruction techniques
- Orthopedic Surgery and Rehabilitation
- Tissue Engineering and Regenerative Medicine
- Single-cell and spatial transcriptomics
- Biomarkers in Disease Mechanisms
- Psoriasis: Treatment and Pathogenesis
- Neonatal Respiratory Health Research
- Electrospun Nanofibers in Biomedical Applications
- Immune Response and Inflammation
- Bone Tissue Engineering Materials
University of Oxford
2016-2025
Nuffield Orthopaedic Centre
2016-2025
Oxford BioMedica (United Kingdom)
2015-2020
NIHR Oxford Musculoskeletal Biomedical Research Centre
2015-2018
Google (United States)
2018
Nuffield Health
2017
National Institute for Health Research
2017
Royal Veterinary College
2009-2015
University of London
2013
Animal Health Trust
2009-2010
Improved understanding of the role inflammation in tendon disease is required to facilitate therapeutic target discovery. We studied supraspinatus tendons from patients experiencing pain before and after surgical subacromial decompression treatment. Tendons were classified as having early, intermediate, or advanced disease, was characterized through activation pathways mediated by interferon (IFN), nuclear factor κB (NF-κB), glucocorticoid receptor, signal transducer activator transcription...
Background Recent investigation of human tissue and cells from positional tendons such as the rotator cuff has clarified importance inflammation in development progression tendon disease. These mechanisms remain poorly understood disease energy-storing Achilles. Using biopsies patients, we investigated if is a feature Achilles tendinopathy rupture. Methods We studied symptomatic patients with either mid-portion or rupture for evidence abnormal inflammatory signatures. Tendon-derived stromal...
Clonal hematopoiesis (CH) arises when hematopoietic stem cells (HSCs) acquire mutations, most frequently in the DNMT3A and TET2 genes, conferring a competitive advantage through mechanisms that remain unclear. To gain insight into how CH mutations enable gradual clonal expansion, we used single-cell multi-omics with high-fidelity genotyping on human bone marrow (BM) samples. Most of selective mutant occurs within HSCs. DNMT3A- TET2-mutant clones expand further early progenitors, while...
Abstract Frozen shoulder is a spontaneously self-resolving chronic inflammatory fibrotic human disease, which distinguishes the condition from most diseases that are progressive and irreversible. Using single-cell analysis, we identify pro-inflammatory MERTK low CD48 + macrophages LYVE1 MRC1+ enriched for negative regulators of inflammation co-exist in frozen capsule tissues. Micro-cultures patient-derived cells integrin-mediated cell-matrix interactions between MERTK+ pro-resolving DKK3+...
Tendon injuries are a common age-related degenerative condition where current treatment strategies fail to restore functionality and normal quality of life. This disease also occurs naturally in horses, with many similarities human tendinopathy making it an ideal large animal model for disease. Regenerative approaches increasingly used improve outcome involving mesenchymal stem cells (MSCs), supported by clinical data injection autologous bone marrow derived MSCs (BM-MSCs) suspended...
Background and purpose — There is a need to understand the reasons why high proportion of rotator cuff repairs fail heal. Using data from large randomized clinical trial, we evaluated age tear size as risk factors for failure repair. Patients methods Between 2007 2014, 65 surgeons 47 hospitals in National Health Service (NHS) recruited 447 patients with atraumatic tendon tears United Kingdom Rotator Cuff Trial (UKUFF) 256 underwent integrity was assessed by imaging 217 patients, at 12 months...
Tendinopathy accounts for over 30% of primary care consultations and represents a growing healthcare challenge in an active increasingly ageing population. Recognising critical cells involved tendinopathy is essential developing therapeutics to meet this challenge. Tendon are heterogenous sparsely distributed dense collagen matrix; limiting previous methods investigate cell characteristics ex vivo. We applied next generation CITE-sequencing; combining surface proteomics with in-depth,...
Growing evidence supports a key role for inflammation in the onset and progression of tendinopathy. However, effect inflammatory infiltrate on tendon cells is poorly understood. We investigated stromal fibroblast activation signatures tissues from patients with Diseased tendons were collected well-phenotyped patient cohorts supraspinatus tendinopathy before after sub-acromial decompression treatment. Healthy undergoing shoulder stabilisation or anterior cruciate ligament repair. Stromal...
Macrophages (Mφ) orchestrate inflammatory and reparatory processes in injured connective tissues but their role during different phases of tendon healing is not known. We investigated the contribution Mφ subsets an equine model naturally occurring injury. Post mortem were harvested from normal (uninjured), sub-acute (3–6 weeks post injury) chronically (>3 months superficial digital flexor tendons. To determine if inflammation was present tendons, sub-populations quantified based on surface...
Background: Platelet-rich plasma (PRP) has been proposed to augment tendon healing through improving tissue structure during the initial repair phase. Purpose: To investigate both clinical and effects of coapplication PRP injection with arthroscopic acromioplasty (AA) in patients chronic rotator cuff tendinopathy. Design: Randomized controlled trial; Level evidence, 1. Methods: The study comprised 60 randomized diagnosed tendinopathy (55% women) aged between 35 75 years. Patients were AA...
Emerging evidence indicates that tendon disease is an active process with inflammation critical to onset and progression. However, the key cytokines responsible for driving sustaining have not been identified.We performed a systematic review of literature using MEDLINE (U.S. National Library Medicine, Bethesda, Maryland) in March 2017. Studies reporting expression interleukins (ILs), tumour necrosis factor alpha (TNF-α) interferon gamma diseased human tissues, animal models injury or...
Purpose Osteoarthritis (OA) is a common and heterogeneous arthritic disorder. Patients suffer pain their joints are characterized by articular cartilage loss osteophyte formation. Risk factors for OA include age obesity with inflammation identified as key mediator of disease pathogenesis. Interleukin-17A (IL-17) pro-inflammatory cytokine that has been implicated in inflammatory diseases such rheumatoid arthritis. IL-17 can upregulate expression cytokines adipocytokines. The aim this study...
The translocator protein (TSPO) is a mitochondrial membrane protein, of as yet uncertain function. Its purported high expression on activated macrophages, has lent utility to TSPO targeted molecular imaging in the form positron emission tomography (PET), means detect and quantify inflammation vivo. However, existing literature regarding human macrophages lacking, mostly deriving from brain tissue studies, including studies malignancy, inflammatory diseases such multiple sclerosis. Here, we...
Increased interleukin (IL)-17A has been identified in joints affected by osteoarthritis (OA), but it is unclear how IL-17A, and its family members IL-17AF IL-17F, can contribute to human OA pathophysiology. Therefore, we aimed evaluate the gene expression signalling pathway activation effects of different IL-17 chondrocytes synovial fibroblasts derived from cartilage synovium patients with end-stage knee OA. Immunohistochemistry staining confirmed that receptor A (IL-17RA) IL-17RC are...
The contribution of inflammation to the pathogenesis tendinopathy and high prevalence re-injury is not well established, although recent evidence suggests involvement prostaglandins. We investigated roles prostaglandins inflammation-resolving mediators in naturally occurring equine tendon injury with disease stage age. Levels E2 (PGE2), F2α (PGF2α), lipoxin A4 (LXA4) its receptor FPR2/ALX were analysed extracts normal, sub-acute chronic injured tendons. To assess whether potential changes...
PET radioligands targeted to translocator protein (TSPO) offer a highly sensitive and specific means of imaging joint inflammation in rheumatoid arthritis (RA). Through high expression TSPO on activated macrophages, has been widely reported several studies RA as synovial macrophages vivo. However, this premise does not take into account the ubiquitous TSPO. This study aimed investigate major cellular constituents pannus—monocytes, fibroblastlike synoviocytes (FLS cells), CD4-positive (CD4+)...