NIHRDataInsights/HRCSData huggingface dataset:
Title: ToKa®: A High Precision Patient Specific High Tibial Osteotomy Procedure
Funder: Versus Arthritis

Abstract: Arthritis of the knee is common; in the UK 14% of the population over 40 suffer from radiographic knee arthritis (4.5 million people) with a similar prevalence in most European countries and the USA. It is a cause of significant disability and pain as well as financial burden. For relatively young sufferers treatment options are limited; knee replacement carries a higher risk of failure for younger people and is not recommended at the earlier stages of knee arthritis.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: Surgical Nanoformulations of Injectable PolyNIPAM for Effective Regeneration of Intervertebral Disc (IVD).
Funder: Versus Arthritis

Abstract: We have developed a novel, minimally invasive, pNIPAM/DMAc/Laponite® injectable hydrogel (NPgel). We have demonstrated it can promote MSC differentiation towards nucleus puplosus cells in a hypoxic environment which mimics the native intervertebral disc (IVD)1. We have demonstrated biological factors can be incorporated into the hydrogel enabling delivery to the target site and completed in vivo safety studies demonstrating no toxic effects or immune response. Preliminary loading work demonstrates injection of NPgel restores mechanical properties in an enzyme digested disc. The IVD is a uniquely loaded environment which is not accurately mimicked in animal models ergo we will employ ex vivo loading systems to investigate biological properties and fatigue testing, following the 3Rs principle reducing animal testing. To enable commercialisation of NPgel it is essential to determine behaviour within a loaded environment similar to that seen in human.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: MUSCULOSKELETAL
Title: Development and Evaluation of a Functional Prototype for the Automated Identification of Osteoporotic Vertebral Fractures: VERDICT
Funder: Versus Arthritis

Abstract: Osteoporosis is a common bone disease affecting 1:2 women and 1:5 men. It can lead to vertebral fractures which have a significant impact on quality of life. Early identification is important but challenging. Vertebral fractures; particularly mild fractures, are difficult to diagnose and can go unreported. There is a clear unmet need to improve vertebral fracture identification approaches. The University of Sheffield's Mellanby Centre for Bone Research (MCBR) employs dual energy x-ray absorptiometry (DXA) to identify vertebral fractures using vertebral fracture assessment (VFA). Other institutions have adopted this approach. VFA is safer for patients than spinal radiography as it uses a much lower dose of x-rays. Our previous studies have shown that VFA is as good as spinal radiographs for identifying vertebral fractures. MCBR has developed the algorithm-based qualitative (ABQ) approach where visual examinations of the vertebral endplate are performed [1]. ABQ also considers variation in the size and shape of vertebrae; other available methods do not do this. ABQ has now become part of standard clinical practice at the Metabolic Bone Centre (MBC), in Sheffield [2]. However, extensive training of healthcare professionals is essential prior to its use. It would be an advance if this process could be automated.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: SHINE: Screening the Hips In NEwborns - The use of an acoustic device to identify developmental hip dysplasia in babies
Funder: Versus Arthritis

Abstract: Developmental dysplasia of the hip (DDH) is a spectrum of disease. One per 1000 babies have a frankly dislocated hip, and 2-3% are diagnosed with some degree of hip dysplasia. DDH is associated with premature osteoarthritis and is the reason for 10% of all hip replacements, and is the most commonly identified cause of hip osteoarthritis in those under 60 years old. Early diagnosis is crucial to determine whether surgery is required in childhood, and to maximise adulthood outcomes. If DDH is identified early in infancy it can usually be rectified with a removable splint, worn for just a few weeks.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: In vivo Proof-of-Concept for a new bio-inspired resorbable non-delaminating construct for osteochondral repair using a large animal model of joint damage.
Funder: Versus Arthritis

Abstract: This PoC will enable the preclinical development of a new cost-effective multilayer functional scaffold for joint surface regeneration, i.e. the osteochondral region, in patients with localised moderate osteoarthritis and post-traumatic osteochondral defects. Early intervention using Minimally Invasive Surgery is available for joints with easy access, e.g. the knee. Treatment includes microfracture and a limited range of orthobiological products, including scaffold-based implants which represent promising options for focal articular repair.


Research activity codes: 5.2 CELLULAR AND GENE THERAPIES
Health categories: MUSCULOSKELETAL
Title: Exploring brain networks and patient descriptions of body perception related musculoskeletal pain to discover new targets for future treatment.
Funder: Versus Arthritis

Abstract: Pain is the primary concern for those with musculoskeletal (MSK) conditions as it considerably impacts on their daily lives and ability to function. Yet current treatments for persistent pain relief have limited effect and are costly to tightening NHS budgets. Recent evidence that ‘virtually’ changing hand appearance using illusions significantly reduces hand pain in MSK conditions, suggesting potential for new treatment directions. However, the brain processes responsible for this rapid pain reduction during the illusion are currently unknown. It is this discovery that forms the basis of our project.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;6.6 PSYCHOLOGICAL AND BEHAVIOURAL;2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: MUSCULOSKELETAL
Title: Can we predict risk of knee pain and painful osteoarthritis following knee joint injury?
Funder: Versus Arthritis

Abstract: Background: Osteoarthritis (OA) is the commonest cause of chronic joint pain in the UK, and the knee is most commonly affected joint. Joint injury is the biggest risk factor for knee OA. This includes sporting injuries such as rupture of the anterior cruciate ligament (ACL). An estimated 50% of those with a substantial knee injury will develop painful osteoarthritis over 5-10 years, and many others will experience knee joint pain. The relationship between onset of knee pain and structural change is complex and not well understood; this can be studied over time in cohorts with knee injury, such as the Knee Injury Cohort at the Kennedy (KICK) study. Currently, we are not able to identify those at high risk of either pain or arthritis after knee injury.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: Validating a new model of nociceptive plasticity affecting chronic pain
Funder: Versus Arthritis

Abstract: Many patients with musculoskeletal disorders (e.g. osteoarthritis, OA; fibromyalgia, FM) suffer severe pain that, for a number of possible reasons, is poorly managed with pharmacological or surgical treatments. It is widely thought that in some cases, central mechanisms of nociceptive plasticity may contribute to pain and treatment resistance. We plan to develop and validate biologically-plausible computational models of nociceptive plasticity that have potential to be developed into practicable clinical tests for screening, diagnosis and treatment stratification.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: Semaphorin 3A / new target for controlling joint pain?
Funder: Versus Arthritis

Abstract: Around 10 million people in the UK are affected by joint pain, osteoarthritis (OA) representing the most frequent condition. Joint pain becomes more prevalent with the ageing population. Current management of joint diseases doesn’t meet patients’ needs in terms of providing adequate and sustained pain relief and this has major detrimental effect on their quality of life. Exercise and physical activity are often the sole remedies for the management of joint pain. There is still a very poor understanding of the mechanisms that drive joint pain but in many skeletal diseases, pain is associated with pathological nerve ingrowth forming neuroma-like structures. What drives this nerve sprouting? Semaphorins are a family of signalling molecules that work as guidance cues for nerve growth. Our preliminary data have shown that one secreted member of this family, semaphorin-3A (sema-3A), which is osteoprotective and acts as a chemo-repellent for growth and sprouting of sensory neurons, is expressed in articular chondrocytes and is down-regulated in OA and by ageing. This project will test the hypothesis that a reduction of sema-3A expression in the joint leads to uncontrolled local nerve ingrowth and joint pain, which can be attenuated by sema-3A administration without exacerbating disease progression.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL
Title: Exploring repetition suppression of sensory evoked potentials associated with the location of pain in patients with fibromyalgia (RS-Fibro)
Funder: Versus Arthritis

Abstract: Fibromyalgia is a chronic pain disorder that is characterised not only by the widespread nature of muscular pain but also by other distressing somatic symptoms. It is increasingly considered a disorder of the central nervous system, and current research strongly suggest the loss of inhibitory control as a key mechanism for the symptom of widespread pain. Neuroscientific research has focused primarily on the nociceptive system and its relationship to pain by studying neural activity during noxious stimulation in patients with fibromyalgia. Less is known about how pain-relevant signals from other sensory modalities are processed neurally. In this project, we seek to understand how the brain processes tactile and auditory stimuli that are located at, or near sites of bodily pain.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: The role of TRPM3 in the development and maintenance of pain in osteoarthritis
Funder: Versus Arthritis

Abstract: Pain associated with osteoarthritis (OA) is poorly treated by existing drugs and new analgesic therapies are needed. Inhibition of TRPM3 is a potentially important mechanism for OA pain relief. Genetic deletion or pharmacological inhibition of TRPM3 can reverse painful sensory hypersensitivities in neuropathic and inflammatory conditions but the effectiveness of this approach to treat joint pain associated with OA has not been established. The proposed studies will use a combination of genetic and pharmacological approaches to determine the role of TRPM3 in the development and, importantly, the maintenance of OA pain using a medial meniscectomy model of surgically-induced OA. The development of pain and sensory hypersensitivities after unilateral meniscectomy will be followed in TRPM3 knockout (Trpm3-/-) and wild-type mice using weight bearing, vocalization to knee flexion, and referred mechanical (paw pressure and von Frey) and cold sensitivities in the paw of the affected leg. We will then determine if OA-related pain can be reversed after the painful hypersensitivities have developed by genetically deleting TRPM3 using a Cre-Lox approach with mice expressing both floxed TRPM3 and Cre recombinase under the control of a tamoxifen inducible ERT2 gene. OA pain will be surgically induced in these mice and tamoxifen administered after painful hypersensitivities have developed to delete TRPM3 from all cells in the body. Additionally, small molecule inhibitors of TRPM3 will be administered systemically to wild-type mice with OA pain. These two lines of experimentation will determine if established OA pain can be reversed by TRPM3 inhibition. We will also determine the expression of TRPM3 in joint tissues and sensory neurons innervating the joint normally and after meniscectomy. The Cre-Lox approach will then be used to elucidate if specific deletion of TRPM3 from sensory neurons (using floxed TRPM3, Advillin-Cre/ERT2 mice) after the development of OA pain will reverse hypersensitivities. In addition, we will determine if deleting TRPM3 locally in the joint by local intra-articular injection of a virus (AAV9) expressing Cre-recombinase into floxed TRPM3 mouse joints, or pharmacological inhibition of TRPM3, can inhibit the maintenance of OA-related pain hypersensitivities.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL
Title: Targeting of matrix catabolism through a novel IFT-LRP interaction
Funder: Versus Arthritis

Abstract: Arthritis is often defined by protease destruction of cartilage matrix. This project will investigate protease regulation by the ciliome with a view towards therapeutic exploitation.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.1 PHARMACEUTICALS;1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: MUSCULOSKELETAL
Title: The role of the microRNA-29 family in osteoarthritis
Funder: Versus Arthritis

Abstract: Our hypothesis is that the microRNA-29 family have a key role in chondrocytes in skeletal development and in regulating cartilage homeostasis in OA. We recently identified the early regulation of miR-29b-3p post-DMM surgery in an opposite direction to its potential targets. The miR-29 family consists of two alleles, miR-29-a/b1 and miR-29-b2/c, giving three mature miRs (29a, b and c) with identical seed sequences. The miR-29 family were also regulated in a model of cartilage injury and in end-stage human OA cartilage. We showed that, in chondrocytes, the miR-29 family is repressed by Sox9 and TGFß, but increased by IL-1. The miR-29 family negatively regulated Smad, NF?B and canonical WNT signalling pathways. Having established clear functions for the miR-29 family in cartilage in vitro, this project now addresses their role in vivo. Using cartilage-specific null mice (for each allele and the double knockout), we propose to assess the impact of the miR-29 family on skeletal development, spontaneous OA and in the DMM model. Understanding function in vivo is a prelude to developing a therapeutic approach in man.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: The role of gender, menopause and sex hormones in painful hand osteoarthritis
Funder: Versus Arthritis

Abstract: 2 million people in the UK have painful hand OA: 8% of women and 3% of men over 45 years of age. Hand symptoms may resolve or persist, affecting quality of life. In women, it tends to develop around the time of the menopause, suggesting changes in sex hormones are biologically important in its evolution.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: MUSCULOSKELETAL
Title: Neuronal basis of the transition of acute to chronic musculoskeletal pain
Funder: Versus Arthritis

Abstract: Pain is arguably the biggest problem associated with musculoskeletal disorders, but pain relief remains poor. A better understanding of physiological mechanisms underlying musculoskeletal pain is necessary to address this unmet need for improved analgesic treatments. Excitability of sensory neurones is an important determinant of a peripheral drive that produces central sensitisation and contributes to chronic pain, and the heterogeneity of sensory neurones has become more apparent with recent advances in single-cell transcriptomics. However, it still remains unclear which specific subsets of peripheral sensory neurones drive musculoskeletal pain.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: NC3R Crackit
Funder: Versus Arthritis

Abstract: Development of a new screening method for potential osteoarthritis treatments Public Summary What are the aims of this research? The task, set by the NC3Rs CRACK IT challenge, which this research aims to address, is the development of a device based on human tissue or cells for research and drug development in osteoarthritis, as an alternative to animal research. Why is this research important? There is an urgent need for relevant human osteoarthritis models for use in research. Currently it is not possible to study all aspects of this only by studying samples taken from people with arthritis and as such researchers end up needing to use animals with arthritis. As human osteoarthritis is difficult to replicate in animals, this is not ideal, therefore these researchers are looking at using cells to create a model of osteoarthritis. This model will be able to be used to test potential new drugs, and therefore replace the need for animal testing of these new treatments. Cells will be used to represent different parts of a human joint and will be placed in a microfluidic device, which means that the cells will be able to communicate with one another as they normally do in a joint. The researchers will create 3D cell models, by “printing” the different types of joint cells and using varying amounts of particular cells to create specific models that represent the different stages of osteoarthritis; from mild disease to severe. They will then be able to test different drugs and assess their ability to stop or reverse osteoarthritis. How will this research benefit people with arthritis? This research will develop a new way of screening drugs for osteoarthritis that is more applicable to real life human osteoarthritis. This means that the experiments are more reliable, more cost-efficient and could lead to quicker development of drugs for use in osteoarthritis. The system will also reduce the number of animals used in osteoarthritis research.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: MUSCULOSKELETAL
Title: A dietary intervention trial to examine the protective effect of broccoli bioactives (specifically sulforaphane) on osteoarthritis
Funder: Versus Arthritis

Abstract: There is increasingly strong evidence from laboratory studies to indicate a protective role for sulforaphane in the biological processes underlying cartilage degeneration, and data indicates that therapeutically active levels in joint tissues can be achieved through the diet.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL
Title: Suramin - a new hope for blocking osteoarthritic cartilage loss?
Funder: Versus Arthritis

Abstract: Our goal is to develop a disease-modifying osteoarthritis (OA) therapy that can protect cartilage against metalloproteinase-driven degradation by increasing levels of the chondroprotective tissue inhibitor of metalloproteinases 3 (TIMP-3). Timp3-/- mice develop accelerated spontaneous OA, underscoring the important role this inhibitor plays in counteracting aggrecanase- and collagenase-driven loss of the cartilage extracellular matrix, a key event in the pathogenesis of OA. Conversely, administration of recombinant TIMP-3 into the joint protects cartilage in a rat OA model. TIMP-3 levels are known to drop in OA cartilage, and Troeberg (PI) has established that TIMP-3 is regulated post-translationally by endocytosis and lysosomal degradation, driven by the low-density lipoprotein receptor-related protein 1 (LRP1).


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL
Title: Systemic sclerosis-related calcinosis: developing safe, effective topical treatments to reduce pain, ulceration and disability (TOPiCAL)
Funder: Versus Arthritis

Abstract: Background. Calcinosis (deposition of subcutaneous calcium-containing lumps) occurs in 20-40% of patients with systemic sclerosis (SSc, also termed 'scleroderma’). Calcinotic lumps can be a huge burden in terms of pain, disability, and unsightliness: currently there is no effective treatment.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL
Title: Feeling it in your bones: mapping early bone marrow lesion and pain development in spontaneous and load-induced mouse models of OA
Funder: Versus Arthritis

Abstract: Osteoarthritis (OA) is a debilitating condition involving multiple joint changes, including cartilage degradation and bone marrow lesions (BML). OA pain afflicts >8.5 million UK citizens and whilst its origins remain obscure, recent studies link pain to BML presence, size and number. Defining BML origins and their link to OA pain is of paramount importance. A longitudinal study in an animal model is therefore the logical next step. Our pilot data in STR/ort mice indicate BML formation that is spatially-linked to the OA arising spontaneously in this model. Our histological observations in STR/ort mice and in early/advanced human OA lead us to hypothesise that: BML develop in locations subject to OA-related changes in the subchondral mechanical environment, are preceded by a highly vascularised and innervated stage, and coincide with pain onset.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: An integrated approach to joint disease across the lifespan
Funder: Versus Arthritis

Abstract: Osteoarthritis and related conditions affect millions of people in the UK, leading to decreased quality of life for sufferers. There is currently no cure for osteoarthritis and a paucity of pharmaceutical options. Osteoarthritis has a complex etiology with a strong genetic component and associations with obesity and the immune system in addition to wear and tear of the joint. Understanding how genes identified from association studies function at a cellular level and how they interact with the functional joint environment (e.g. with loading and the immune system) offer the best prospect for prioritising targets for drug development.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: MUSCULOSKELETAL
Title: Development of Link_TSG6 as a novel disease-modifying protein biological for osteoarthritis with analgesic effects: pre-clinical evaluation to facilitate commercial partnering and clinical trials
Funder: Versus Arthritis

Abstract: We have discovered that Link_TSG6 (the Link module of human TSG-6) inhibits cartilage damage, inflammation and pain, as well as supressing bone loss. The aim of this proposal is to facilitate the translation of Link_TSG6 to the clinic as a disease-modifying/analgesic treatment for osteoarthritis. We will utilise two different mouse models of OA, as well as models of pain, and human OA cartilage explants to generate efficacy, dose-response and PK data that will inform the design of future PK/PD studies and clinical trials. Mechanism-of-action studies will determine whether Link_TSG6’s interaction with the chemokine CCL2 underpins its beneficial effects on inflammation/pain.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: MUSCULOSKELETAL