NIHRDataInsights/HRCSData huggingface dataset:
Title: Biomarkers and Joint Pain in Military Osteoarthritis Study (Bio-Mil-OA)
Funder: Versus Arthritis

Abstract: Background: Trauma is a well recognised risk factor for the future development of osteoarthritis (OA). The Armed Services Trauma and Rehabilitation outcome study (The ADVANCE study) is a 20 year cohort study comparing medical and psychosocial outcomes of military personnel both exposed and not exposed, to significant trauma. The Bio-Mil-OA study, a sub-study of the ADVANCE study, is an ideal opportunity to investigate the predictive value of biomarkers in joint pain and osteoarthritis. Methods: This is a 20 year cohort study of 600 combat casualties and 600 matched non exposed participants investigating the predictive value of biomarkers and trauma on the long term development of pain and OA in the hip and knee. Validated serum biomarkers for OA, knee and hip radiographs and patient reported outcomes for pain and function will be taken at baseline and at 5 years. The predictive value of the biomarkers in predicting OA development and progression and joint pain in those exposed to different levels of trauma will be investigated using quantitative immunoassays for catabolic markers of cartilage matrix degradation. Key Goals: To investigate the predictive value of biomarkers in the development and progression of OA and joint pain outcomes in “high risk” military personnel.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: Engineering Physiological Complexity into Osteochondral Tissue Using Externally Aligned Cells and Growth Factors
Funder: Versus Arthritis

Abstract: Tissue engineering represents a major strategy for repairing degenerated osteochondral tissue in osteoarthritic joints. Replicating the microstructural complexity of physiological osteochondral tissue is critical for the successful integration and function of implanted engineered constructs. Here, we propose engineering complex osteochondral tissue by aligning cells and growth factors using acoustic waves and magnetic fields, respectively. Specifically, we intend to use magnetic fields to establish biochemical gradients of osteogenic and chondrogenic growth factors in scaffolds and gels, and acoustic trapping to align chondrocytes into the columnar arrangement present in radial zone cartilage. We will investigate the impact of cellular alignment and growth factor distribution upon the organisation of ECM fibres in engineered cartilage. It follows that if we mimic the physiological cellular distribution, we will be able to improve the mechanical function of engineered cartilage constructs.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: MUSCULOSKELETAL
Title: The application of Raman arthrospectroscopy for intra-operative mapping of early articular cartilage degeneration
Funder: Versus Arthritis

Abstract: What are the aims of this research?_x000D_ A device to identify early onset of cartilage damage during osteoarthritis is in its early developmental stages. The aim of this research is to continue to develop this technology towards commercial production._x000D_ _x000D_ Why is this research important? _x000D_ Currently detection of cartilage damage in osteoarthritis is mainly by x-rays which require significant damage to have occurred to the cartilage. Slightly earlier detection is available using MRI scans however this is seldom used due to the cost and also the required expertise of the technician to interpret the results. There is therefore a need for technology to identify the disease earlier._x000D_ This research has demonstrated that the changes in cartilage that occur in very early disease can be identified with a technology called Raman spectroscopy. This technology uses laser lights directed at the tissue to scan the molecules in the tissue which provides detailed information on the joint. This is a highly sensitive method which is minimally invasive and non-destructive to the tissues._x000D_ _x000D_ How will the findings benefit patients?_x000D_ This technology will enable surgeons to make an objective assessment of the joint rather than relying on variable assessments from the opinion of the surgeon. The reduced cost of this technology would mean that it could be used as a routine assessment tool to look at cartilage health, which will assist with surgical choice and therefore help patients avoid the trauma of revision surgery as well as reducing costs.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: Resolving the Genetic Architecture of Aseptic Loosening After Total Hip Replacement
Funder: Versus Arthritis

Abstract: Aseptic loosening, an adverse local tissue response to prosthesis materials, is the most common reason for total hip arthroplasty (THA) failure. Revision surgery is associated with higher costs, morbidity, mortality, and poorer functional outcomes than primary THA surgery. The incidence of aseptic loosening differs between individuals, due in part to genetic factors. The overall aim of this project is to create a detailed picture of the genetic architecture of aseptic loosening as a platform for novel predictive and diagnostic biomarkers and therapeutic solution discovery for patient benefit.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: Generation and Characterisation of Induced Pluripotent Stem Cell-Derived Notochordal Cells
Funder: Versus Arthritis

Abstract: Back pain is a leading cause of disability in the UK and intervertebral disc (IVD) degeneration has been identified as the cause in a high proportion of patients. As current therapies for chronic back pain demonstrate poor long-term efficacy, there is an urgent clinical need for advanced, cell-based therapies to regenerate IVD tissue, restore function and treat back pain. As the central nucleus pulposus (NP) region originates from notochordal cells (NCs), we hypothesise that NCs may be the ideal cell source for IVD regeneration. However, since human NCs are lost during early life, we aim to develop a method to differentiate human induced pluripotent stem cells (iPSCs) to NCs (iNCs), which could be used as a cell therapy for IVD degeneration. To achieve this we aim to (i) characterise the transcriptomic and proteomic profile of human foetal NCs; (ii) optimise a method to differentiate iPSCs to NCs; and (iii) assess the functional characteristics of iNCs compared to native NCs. The findings from this study will provide a vital international resource on human NC phenotype and an infinite source of iNCs for future study and development of a cell-based therapy to treat IVD degeneration and back pain.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;1.4 METHODOLOGIES AND MEASUREMENTS
Health categories: MUSCULOSKELETAL
Title: Viscero-sensory processes and neural responses to inflammation: mechanisms of pain and fatigue in fibromyalgia
Funder: Versus Arthritis

Abstract: In fibromyalgia, in addition to pain, patients frequently report a variety of extra-musculoskeletal features, primarily physical and emotional fatigue including cognitive dysfunction (often termed ‘fibrofog’). Patients with fibromyalgia (5% of population) score significantly lower in health status quality of life domains than either those in the general population or patients with other musculo-skeletal disorders such as rheumatoid arthritis. Symptom domains that have the greatest impact on quality of life include pain, fatigue, cognitive impairment and psychological disturbance. Patients with fibromyalgia report more cognitive difficulties than patients with any other rheumatological disorder and show evidence of sympathetic nervous hyperactivity. This study aims to investigate for the first time the contribution of altered viscero-sensory processes (particularly dysautonomia and altered interoceptive proceses) and neural responses to inflammation to pain and fatigue, particularly mental fatigue. We aim to provide a mechanistic account for pain and fatigue in fibromyalgia by the means of two physiological challenges (one autonomic, the other inflammatory) and demonstrate altered markers of inflammation, including in the brain, in fibromyalgia. This has great potential impact in not only understanding mechanisms of pain and fatigue in these patients but also identifying novel treatment targets and improving quality of life.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: Characterising the molecular changes underpinning osteophyte formation and disc degeneration
Funder: Versus Arthritis

Abstract: Spinal osteoarthritis, or spondylosis, is a common forms of osteoarthritis and a major cause of chronic back pain, for which there are relatively few treatment options. Spondylosis is characterised by bone changes such as disc space narrowing and formation of osteophytes.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: The tendon interfascicular matrix: a mechanically unique tendon progenitor cell niche
Funder: Versus Arthritis

Abstract: Tendinopathy is a common age-related condition for which current treatment remains limited. Development of more effective treatments requires comprehensive knowledge of tendon cell populations and their role in maintaining homeostasis and repairing damage, information which is currently lacking. I believe that tendon homeostasis and repair is coordinated by progenitors maintained by the unique mechanical environment provided by the interfascicular matrix (IFM) niche. I will determine the location of, and identify novel markers for, the progenitor niche using laser capture microdissection combined with genomics and proteomics. I will also use established progenitor markers to determine if the progenitor niche is conserved across tissues. I will then assess proteome dynamics using in vivo isotopic labelling combined with mass spectrometry to determine if tendon homeostasis is maintained by preferential remodelling of the IFM. Then I will use a rat Achilles injury model to track the response of IFM and circulating progenitor populations to injury and determine progenitor recruitment during repair. Finally, I will isolate the IFM progenitor population and apply controlled tension and shear in a 3D loading system, assessing alterations in cell phenotype to determine if IFM progenitor phenotype is maintained by unique mechanical cues.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: MUSCULOSKELETAL
Title: Cloudy with a Chance of Pain
Funder: Versus Arthritis

Abstract: ‘Cloudy with a Chance of Pain’ is a large national prospective population study in patients with chronic musculoskeletal pain to answer the age-old question of whether the weather influences symptoms of arthritis and other chronic pain. It will use participants’ own technology to collect symptom data alongside hourly information about the weather at their location. Integral to engagement in the study is a citizen science experiment. Study participants and the general public will be able to view study data in real-time and submit hypotheses about relationships in the data that they identify. The output of the project will be an understanding of the association between weather and pain. Ultimately, this may support symptom forecasting, and will feed back into a more basic understanding of what drives pain in patients with arthritis and potential development of novel interventions.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: MUSCULOSKELETAL
Title: Does the beneficial effect of maternal gestational vitamin D supplementation on neonatal bone mass persist into childhood? Follow-up of the MAVIDOS placebo-controlled, double-blind, randomised trial.
Funder: Versus Arthritis

Abstract: There is increasing evidence that poor bone development in utero is a risk factor for osteoporotic fracture in older age. We have demonstrated in a unique multi-centre double-blind, placebo-controlled, randomised trial (MAVIDOS), funded by Arthritis Research UK, that vitamin D supplementation during pregnancy leads to improved bone mass in babies born during winter months. In order for this result to fully inform national and international public health policy, it is essential to establish whether these benefits are maintained into older childhood. We now request modest adjunctive funding to test whether differences in bone mineral content and bone mineral density between neonates born to treatment and placebo mothers persist at 6 years old, taking into account postnatal diet, lifestyle, physical activity and health; and secondly to investigate underlying mechanisms by characterisation of bone microarchitecture using high-resolution pQCT and assessment of biochemical markers and epigenetic regulation. This study permits a unique opportunity to establish the persistent benefit and safety of vitamin D supplementation in pregnancy, and is very likely to inform global public health policy.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: MUSCULOSKELETAL
Title: Harnessing clay gels and droplet microfluidics for cartilage tissue engineering
Funder: Versus Arthritis

Abstract: Bone marrow stromal cells (BMSCs) are a promising cell source for cartilage tissue engineering. However, high variability in the chondrogenic potential of BMSCs is frequently reported, resulting in chondrocyte hypertrophy, generation of mechanically inferior fibrocartilage and/or the problematic occurrence of tissue calcification. Two significant limitations underlie this problem: 1) We lack the know-how and means to define local microenvironments able to promote stable chondrogenesis by BMSCs 2) We lack reliable markers to enrich subpopulations with robust chondrogenic potential from heterogeneous BMSCs. We propose an approach to address both these challenges by combining clay gels with droplet microfluidics.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: MUSCULOSKELETAL
Title: Targeting alarmins to accelerate fracture healing in osteoporotic bone.
Funder: Versus Arthritis

Abstract: Fractures in osteoporotic bone are extremely common and the prevalence is increasing due to the aging population. These fragility fractures are associated with high rates of morbidity and mortality and there is an urgent unmet need as currently there is no approved therapy for accelerating their healing. We have recently shown the crucial role of neutrophils in fracture healing and that targeted upregulation of the pro-inflammatory cytokine TNF in the first 24h after injury leads to accelerated fracture healing in normal and in osteoporotic bone. Alarmins are passively released by dying cells after tissue injury or rapidly secreted by stimulated leukocytes. Based on our preliminary data, the alarmin pathways, which mediate the initial innate immune response, represent potential therapeutic targets. Our aim is to identify the alarmin pathways that provide the optimal microenvironment for repair to develop a therapeutic agent that will accelerate fracture healing in osteoporotic bone. The role of alarmins will be investigated by in vivo and in vitro experiments, including inhibition or exogenous addition of HMGB1 or S100A8 in our murine fracture model, measuring alarmin levels following injury in murine and human samples and determining the effect of alarmins on the recruitment and differentiation of osteogenic precursors.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL
Title: ORCHID STUDY - Outcome Research in Children’s HIp Disease
Funder: Versus Arthritis

Abstract: The childhood diseases Legg-Calve-Perthes disease and Slipped Capital Femoral Epiphysis significantly alter the shape of the proximal femur. These diseases cause pain, disability and a significantly increased risk of osteoarthritis. The type of treatments offered to children vary considerably throughout the UK, and may range from simple observation to major surgery. The optimum management of these diseases is uncertain.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: Fibromyalgia Optimal Management for patients with axial Spondyloarthritis (FOMAxS)
Funder: Versus Arthritis

Abstract: The prevalence of fibromyalgia (FM) amongst patients with axial Spondyloarthritis (axSpA) is unknown, but it is conservatively estimated at 15%, three to four times the prevalence in the general population. It is, however, challenging to determine whether widespread pain is arising from axSpA or is because of FM as a comorbidity. Observations suggest that FM may distort responses to some key patient-reported measures used in axSpA and as a result such patients may receive inappropriate management, a concern emphasised in a recent US Food and Drug Administration review. This highlights the need to understand what characterises patients with overlapping axSpA and FM, to be able to assess and distinguish the conditions, and to develop effective treatment strategies for patients with both conditions.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: MUSCULOSKELETAL
Title: Osteoarthritis Preoperative Package of care of Orthotics, Rehabilitation, Topical and oral agent Usage and Nutrition to Improve outcomes aT a Year (OPPORTUNITY)
Funder: Versus Arthritis

Abstract: The overall purpose of this research is to take advantage of the incentive for behavioural change in patients with osteoarthritis (OA), who have been placed on the waiting list for orthopaedic surgery, to obtain a durable alteration in the patients’ weight and exercise level. We postulate that the reduction in weight and increased activity coupled with an appropriate analgesia review and attention to footwear in the pre-operative window will result in a sustained improvement in the patient’s health-related quality of life following knee replacement. The aim of this application is to assess the feasibility of running a pivotal randomised controlled trial (RCT) of a pre-operative package of non-operative care versus standard care prior to joint replacement. The objective of this feasibility study is to test the logistics and feasibility of the study methods and intervention delivery as well as the acceptability of the intervention in preparation for the definitive trial.


Research activity codes: 6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION)
Health categories: MUSCULOSKELETAL
Title: Patient direct access to NHS musculoskeletal physiotherapy: what is the impact on patients, general practice and physiotherapy services?
Funder: Versus Arthritis

Abstract: Observational studies into patient direct access to physiotherapy for patients with musculoskeletal (MSK) conditions suggest that it is safe, does not overload physiotherapy services, does not result in inappropriate patients accessing physiotherapy, and is likely to provide outcomes that compare well with traditional GP-led care. However, widespread implementation of patient direct access is lacking, which at least partially results from there being key gaps in the evidence.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.2 HEALTH AND WELFARE ECONOMICS
Health categories: MUSCULOSKELETAL
Title: Providing a standardised approach to virtual clinic follow-up of total joint replacement
Funder: Versus Arthritis

Abstract: Hip and knee total joint replacements (TJRs) are increasing in number each year.1 The guidelines of the British Hip Society and British Association for Surgery of the Knee recommend that patients who have had a TJR are followed up at one year, 5-7 years, and thereafter every 5 years for implants which have met the required standard rating, with more frequent follow-up for novel implants.2-4 The follow-up for one year of hip replacement patients costs £50 million,5 a staggering cost. While the majority of TJRs do well, a small percentage will require revision, though some failing joints are asymptomatic requiring X-rays for problem detection. As well, without timely intervention, revision surgery becomes more complex when it is ultimately required. Furthermore, our Patient and Public Involvement work and recent studies suggest that patients do want to know that there is some level of monitoring of their TJR and that there is in place a robust way of identifying those who require further treatment. Therefore, there needs to be some form of follow-up and care for these patients.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: A feasibility study for Walk with Ease UK – a community-based walking programme for adults with arthritis and musculoskeletal conditions
Funder: Versus Arthritis

Abstract: The benefits of physical activity (PA) on health are undisputed yet physical inactivity remains a major public health challenge throughout the UK and costs the NHS at least £1 billion in direct costs. Despite associated physical and mental health benefits, individuals with arthritis/musculoskeletal (MSK) conditions are less active than those without. They often report pain, fatigue, stiffness and activity limitations, which make engaging in and increasing PA especially challenging. Walking is a safe, easy, and inexpensive activity that is acceptable in those with arthritis/MSK, and can be a means for most adults to achieve currently recommended PA levels. Walk with Ease (WWE) is a walking intervention (developed in the United States) specifically designed for an arthritis/MSK population. It has been shown to be effective in reducing arthritis-related symptoms and improving physical function when delivered in either a group or self-directed format. Based on this, WWE in a UK setting can increase quality of life through increased PA among inactive arthritis/MSK individuals, resulting in reduced health-related economic costs. Our group are experts in implementing and evaluating health-related interventions in arthritis/MSK populations. We will use our specialist skills to bring WWE to the UK and answer fundamental questions that will lead to demonstrable health improvements.


Research activity codes: 6.7 PHYSICAL
Health categories: MUSCULOSKELETAL
Title: Shedding of the endocytic receptor LRP1 in cartilage: A novel link to the development of osteoarthritis.
Funder: Versus Arthritis

Abstract: The hallmark of osteoarthritis (OA) is a shift from normal homeostasis of articular cartilage to a catabolic state, with an increase of cartilage matrix breakdown. I recently discovered that the endocytic receptor, low-density lipoprotein receptor-related protein 1 (LRP1) is a key receptor in maintaining the homeostasis of healthy adult cartilage by controlling extracellular levels of numerous biologically active molecules, but its function is impaired in OA cartilage due to the proteolytic ‘shedding’ of the receptor by two membrane-bound metalloproteinases MMP-14 and ADAM17. I identified 41 new LRP1 ligand candidates in human cartilage, emphasising the key role of LRP1 regulation in cartilage biology. I also found that TGFß increased the protein level of LRP1 in human cartilage. The aims of this fellowship are: 1) to profile all the LRP1 ligands and determine their functions in cartilage; 2) to understand how and when proteolytic activities of LRP1 sheddases are activated during OA progression; and 3) to investigate whether TGFß can restore LRP1 function in OA cartilage. The study will use state-of-the-art proteomics, biochemical, molecular and cell biological techniques. Accomplishment of these aims will establish a new cornerstone for our understanding of OA pathogenesis and the development of novel OA therapeutics.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL