Recognition and Scoring Physical Exercises via Temporal and Relative Analysis of Skeleton Nodes Extracted from the Kinect Sensor.

Human activity recognition is known as the backbone of the development of interactive systems, such as computer games. This process is usually performed by either vision-based or depth sensors. So far, various solutions have been developed for this purpose; however, all the challenges of this process have not been completely resolved. In this paper, a solution based on pattern recognition has been developed for labeling and scoring physical exercises performed in front of the Kinect sensor. Extracting the features from human skeletal joints and then generating relative descriptors among them is the first step of our method. This has led to quantification of the meaningful relationships between different parts of the skeletal joints during exercise performance. In this method, the discriminating descriptors of each exercise motion are used to identify the adaptive kernels of the Constrained Energy Minimization method as a target detector operator. The results indicated an accuracy of 95.9% in the labeling process of physical exercise motions. Scoring the exercise motions was the second step after the labeling process, in which a geometric method was used to interpolate numerical quantities extracted from descriptor vectors to transform into semantic scores. The results demonstrated the scoring process coincided with the scores derived by the sports coach by a 99.5 grade in the R2 index.

A Systematic Review on Rigid Exoskeleton Robot Design for Wearing Comfort: Joint Self-Alignment, Attachment Interface, and Structure Customization.

Exoskeleton robots enable individuals with impaired physical functions to perform daily activities and maintain independence. However, the discomfort experienced by users when using these devices may limit the application scope of exoskeleton robots. Therefore, this paper systematically defines and analyzes the key design factors affecting the wearing comfort of rigid exoskeleton robots by differentiating and discussing the characteristics of traditional exoskeleton robots and exoskeleton robots equipped with the self-alignment mechanism based on addressing misalignment issues. Furthermore, the various structural configurations of the Physical Human-Robot Attachment Interface (PHRAI) and related quantitative evaluation indicators are explored in depth, and the advantages and limitations of structural customized design methods combining parametric design, Three-Dimensional (3D) scanning, and 3D printing technology are evaluated. Finally, the current concerns in the research field and potential solution strategies are proposed, aiming to provide directional guidance to optimize future exoskeleton robots. The research findings are of significant value for enhancing the comfort of wearing exoskeleton robots and provide valuable theoretical and practical references for future research.

Construction and performance evaluation of fully biomimetic hyaline cartilage matrix scaffolds for joint defect regeneration.

Due to the absence of nerves and blood vessels in articular cartilage, its regeneration and repair present a significant and complex challenge in osteoarthritis treatment. Developing a specialized physical and chemical microenvironment supporting cell growth has been difficult in cartilage grafting, especially when aiming for comprehensive biomimetic solutions. Based on previous research, we have designed a tissue-engineered decellularized living hyaline cartilage graft (dLhCG). The study developed a method to improve the hydrophilicity and stiffness of scaffolds by employing chemical grafting techniques and designed a decellularized hyaline cartilage phenotype matrix scaffold for tissue engineering. Here, we reported a method using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride /N-hydroxysuccinimide (EDC/NHS) to achieve the grafting of chondroitin sulfate (CS) onto dLhCG, ultimately producing a tissue-engineered hyaline cartilage graft with the CS (dLhCG/CS). Young's modulus measurements revealed that the cross-linked scaffolds exhibited enhanced mechanical properties. We implanted the cross-linked dLhCG/CS scaffolds into the trochlear region of rat joints and evaluated their functionality through histological analysis and biomechanical tests. After 12 weeks, the dLhCG/CS scaffolds demonstrated excellent bioinductive activity comparable to dLhCG. The regenerated tissue effectively maintained a hyaline cartilage phenotype and exhibited similar mechanical properties, playing a crucial role in cartilage regeneration.

The role of vascular and lymphatic networks in bone and joint homeostasis and pathology.

The vascular and lymphatic systems are integral to maintaining skeletal homeostasis and responding to pathological conditions in bone and joint tissues. This review explores the interplay between blood vessels and lymphatic vessels in bones and joints, focusing on their roles in homeostasis, regeneration, and disease progression. Type H blood vessels, characterized by high expression of CD31 and endomucin, are crucial for coupling angiogenesis with osteogenesis, thus supporting bone homeostasis and repair. These vessels facilitate nutrient delivery and waste removal, and their dysfunction can lead to conditions such as ischemia and arthritis. Recent discoveries have highlighted the presence and significance of lymphatic vessels within bone tissue, challenging the traditional view that bones are devoid of lymphatics. Lymphatic vessels contribute to interstitial fluid regulation, immune cell trafficking, and tissue repair through lymphangiocrine signaling. The pathological alterations in these networks are closely linked to inflammatory joint diseases, emphasizing the need for further research into their co-regulatory mechanisms. This comprehensive review summarizes the current understanding of the structural and functional aspects of vascular and lymphatic networks in bone and joint tissues, their roles in homeostasis, and the implications of their dysfunction in disease. By elucidating the dynamic interactions between these systems, we aim to enhance the understanding of their contributions to skeletal health and disease, potentially informing the development of targeted therapeutic strategies.

Can a simple 0-10 RheuMetric physician estimate of inflammatory activity (DOCINF) depict a detailed swollen joint count (SJC) as accurately as a DAS28 or CDAI in patients with rheumatoid arthritis?

OBJECTIVE: To compare a 0-10 physician subglobal estimate of inflammatory activity (DOCINF) on a RheuMetric checklist to a formal swollen joint count (SJC) and other rheumatoid arthritis (RA) Core data set measures in a disease activity score 28 (DAS28), clinical disease activity index (CDAI), and simplified disease activity index (SDAI) in patients with RA, recognizing that RA measures, index scores and physician global assessment (DOCGL) may be elevated by joint damage and patient distress, independent of inflamamtory activity, and that formal joint counts are not recorded at most routine care visits. METHODS: A cross-sectional study at a routine care visit included a RheuMetric checklist completed by a rheumatologist, with four 0-10 visual numeric scales (VNS) for DOCGL, and three sub-global estimates for inflammatory activity (DOCINF), joint damage (DOCDAM), and patient distress (DOCDIS), e.g., anxiety, depression, and/or fibromyalgia, etc. Variation in SJC according to other individual measures in the DAS28, CDAI, and SDAI, and in the indices was analyzed using Spearman correlation coefficients and regressions with and without DOCINF as an independent variable. RESULTS: In 173 patients with long disease duration, regressions which included individual DAS28, CDAI or SDAI measures and added DOCINF as an independent variable explained 46 % of variation in SJC, compared to 23 % if DOCINF was not included. DOCINF was more explanatory of SJC than even the DAS28 or CDAI indices themselves, although SJC is a component of these indices. CONCLUSION: In routine care RA patients with long disease duration, DOCINF depicts SJC as effectively as RA indices which require 90-100 seconds to record, and may provide a feasible, informative quantitative clinical measure without recording formal joint counts.

Evaluating the Performance of Joint Angle Estimation Algorithms on an Exoskeleton Mock-Up via a Modular Testing Approach.

A common challenge for exoskeleton control is discerning operator intent to provide seamless actuation of the device with the operator. One way to accomplish this is with joint angle estimation algorithms and multiple sensors on the human-machine system. However, the question remains of what can be accomplished with just one sensor. The objective of this study was to deploy a modular testing approach to test the performance of two joint angle estimation models-a kinematic extrapolation algorithm and a Random Forest machine learning algorithm-when each was informed solely with kinematic gait data from a single potentiometer on an ankle exoskeleton mock-up. This study demonstrates (i) the feasibility of implementing a modular approach to exoskeleton mock-up evaluation to promote continuity between testing configurations and (ii) that a Random Forest algorithm yielded lower realized errors of estimated joint angles and a decreased actuation time than the kinematic model when deployed on the physical device.

Validity of Valor Inertial Measurement Unit for Upper and Lower Extremity Joint Angles.

Inertial measurement units (IMU) are increasingly utilized to capture biomechanical measures such as joint kinematics outside traditional biomechanics laboratories. These wearable sensors have been proven to help clinicians and engineers monitor rehabilitation progress, improve prosthesis development, and record human performance in a variety of settings. The Valor IMU aims to offer a portable motion capture alternative to provide reliable and accurate joint kinematics when compared to industry gold standard optical motion capture cameras. However, IMUs can have disturbances in their measurements caused by magnetic fields, drift, and inappropriate calibration routines. Therefore, the purpose of this investigation is to validate the joint angles captured by the Valor IMU in comparison to an optical motion capture system across a variety of movements. Our findings showed mean absolute differences between Valor IMU and Vicon motion capture across all subjects' joint angles. The tasks ranged from 1.81 degrees to 17.46 degrees, the root mean squared errors ranged from 1.89 degrees to 16.62 degrees, and interclass correlation coefficient agreements ranged from 0.57 to 0.99. The results in the current paper further promote the usage of the IMU system outside traditional biomechanical laboratories. Future examinations of this IMU should include smaller, modular IMUs with non-slip Velcro bands and further validation regarding transverse plane joint kinematics such as joint internal/external rotations.

Optimizing long-term joint health in the treatment of hemophilia.

INTRODUCTION: The improved quality of care and increased drug availability have shifted the goal of treating people with hemophilia from life-threatening bleeding prevention to joint health preservation and quality of life amelioration. Many tools are now available to the clinician in order to optimize the management of hemophilic arthropathy. AREAS COVERED: This paper reviews the pivotal role of ultrasound evaluation in early detection of joint bleeding and differential diagnosis of joint pain, with a focus on the feasibility of a long-term monitoring of joint health through the use of artificial intelligence and telemedicine. The literature search methodology included using keywords to search in PubMed and Google Scholar, and articles used were screened by the coauthors of this review. EXPERT OPINION: Joint ultrasound is a practical point-of-care tool with many advantages, including immediate correlation between imaging and clinical presentation, and dynamic evaluation of multiple joints. The potential of telemedicine care, coupled with a point-of-care detection device assisted by artificial intelligence, holds promises for even earlier diagnosis and treatment of joint bleeding. A multidisciplinary approach including early intervention by physical medicine and rehabilitation (PMR) physicians and physiotherapists is crucial to ensure the best possible quality of life for the patient.

Advancements in Subchondral Bone Biomechanics: Insights from Computed Tomography and Micro-Computed Tomography Imaging in Equine Models.

PURPOSE OF REVIEW: This review synthesizes recent advancements in understanding subchondral bone (SCB) biomechanics using computed tomography (CT) and micro-computed tomography (micro-CT) imaging in large animal models, particularly horses. RECENT FINDINGS: Recent studies highlight the complexity of SCB biomechanics, revealing variability in density, microstructure, and biomechanical properties across the depth of SCB from the joint surface, as well as at different joint locations. Early SCB abnormalities have been identified as predictive markers for both osteoarthritis (OA) and stress fractures. The development of standing CT systems has improved the practicality and accuracy of live animal imaging, aiding early diagnosis of SCB pathologies. While imaging advancements have enhanced our understanding of SCB, further research is required to elucidate the underlying mechanisms of joint disease and articular surface failure. Combining imaging with mechanical testing, computational modelling, and artificial intelligence (AI) promises earlier detection and better management of joint disease. Future research should refine these modalities and integrate them into clinical practice to enhance joint health outcomes in veterinary and human medicine.

Recurrent Neural Network Enabled Continuous Motion Estimation of Lower Limb Joints From Incomplete sEMG Signals.

Decoding continuous human motion from surface electromyography (sEMG) in advance is crucial for improving the intelligence of exoskeleton robots. However, incomplete sEMG signals are prevalent on account of unstable data transmission, sensor malfunction, and electrode sheet detachment. These non-ideal factors severely compromise the accuracy of continuous motion recognition and the reliability of clinical applications. To tackle this challenge, this paper develops a multi-task parallel learning framework for continuous motion estimation with incomplete sEMG signals. Concretely, a residual network is incorporated into a recurrent neural network to integrate the information flow of hidden states and reconstruct random and consecutive missing sEMG signals. The attention mechanism is applied for redistributing the distribution of weights. A jointly optimized loss function is devised to enable training the model for simultaneously dealing with signal anomalies/absences and multi-joint continuous motion estimation. The proposed model is implemented for estimating hip, knee, and ankle joint angles of physically competent individuals and patients during diverse exercises. Experimental results indicate that the estimation root-mean-square errors with 60% missing sEMG signals steadily converges to below 5 degrees. Even with multi-channel electrode sheet shedding, our model still demonstrates cutting-edge estimation performance, errors only marginally increase 1 degree.

[Lower limb joint contact forces and ground reaction forces analysis based on Azure Kinect motion capture].

Traditional gait analysis systems are typically complex to operate, lack portability, and involve high equipment costs. This study aims to establish a musculoskeletal dynamics calculation process driven by Azure Kinect. Building upon the full-body model of the Anybody musculoskeletal simulation software and incorporating a foot-ground contact model, the study utilized Azure Kinect-driven skeletal data from depth videos of 10 participants. The in-depth videos were prepossessed to extract keypoint of the participants, which were then adopted as inputs for the musculoskeletal model to compute lower limb joint angles, joint contact forces, and ground reaction forces. To validate the Azure Kinect computational model, the calculated results were compared with kinematic and kinetic data obtained using the traditional Vicon system. The forces in the lower limb joints and the ground reaction forces were normalized by dividing them by the body weight. The lower limb joint angle curves showed a strong correlation with Vicon results (mean ρ values: 0.78 ~ 0.92) but with root mean square errors as high as 5.66°. For lower limb joint force prediction, the model exhibited root mean square errors ranging from 0.44 to 0.68, while ground reaction force root mean square errors ranged from 0.01 to 0.09. The established musculoskeletal dynamics model based on Azure Kinect shows good prediction capabilities for lower limb joint forces and vertical ground reaction forces, but some errors remain in predicting lower limb joint angles.

BDNF sensitizes bone and joint afferent neurons at different stages of MIA-induced osteoarthritis.

There is emerging evidence that Brain Derived Neurotrophic Factor (BDNF), and one of its receptors TrkB, play important roles in the pathogenesis of osteoarthritis (OA) pain. Whilst these studies clearly highlight the potential for targeting BDNF/TrkB signaling to treat OA pain, the mechanism for how BDNF/TrkB signaling contributes to OA pain remains unclear. In this study, we used an animal model of mono-iodoacetate (MIA)-induced OA, in combination with electrophysiology, behavioral testing, Western blot analysis, and retrograde tracing and immunohistochemistry, to identify roles for BDNF/TrkB signaling in the pathogenesis of OA pain. We found that: 1) TrkB is expressed in myelinated medium diameter neurons that innervate the knee joint and bone in naïve animals; 2) peripheral application of BDNF increases the sensitivity of Aδ, but not C knee joint and bone afferent neurons, in response to mechanical stimulation, in naïve animals; 3) BDNF expression increases in synovial tissue in early MIA-induced OA, when pathology is confined to the joint, and in the subchondral bone in late MIA-induced OA, when there is additional damage to the surrounding bone; and 4) TrkB inhibition reverses MIA-induced changes in the sensitivity of Aδ but not C knee joint afferent neurons early in MIA-induced OA, and Aδ but not C bone afferent neurons late in MIA-induced OA. Our findings suggest that BDNF/TrkB signaling may have a role to play in the pathogenesis of OA pain, through effects on knee joint afferent neurons early in disease when there is inflammation confined to the joint, and bone afferent neurons late in disease when there is involvement of damage to subchondral bone. Targeted manipulation of BDNF/TrkB signaling may provide therapeutic benefit for the management of OA pain.

Brazilian fossils reveal homoplasy in the oldest mammalian jaw joint.

The acquisition of the load-bearing dentary-squamosal jaw joint was a key step in mammalian evolution1-5. Although this innovation has received decades of study, questions remain over when and how frequently a mammalian-like skull-jaw contact evolved, hindered by a paucity of three-dimensional data spanning the non-mammaliaform cynodont-mammaliaform transition. New discoveries of derived non-mammaliaform probainognathian cynodonts from South America have much to offer to this discussion. Here, to address this issue, we used micro-computed-tomography scanning to reconstruct the jaw joint anatomy of three key probainognathian cynodonts: Brasilodon quadrangularis, the sister taxon to Mammaliaformes6-8, the tritheledontid-related Riograndia guaibensis9 and the tritylodontid Oligokyphus major. We find homoplastic evolution in the jaw joint in the approach to mammaliaforms, with ictidosaurs (Riograndia plus tritheledontids) independently evolving a dentary-squamosal contact approximately 17 million years before this character first appears in mammaliaforms of the Late Triassic period10-12. Brasilodon, contrary to previous descriptions6-8, lacks an incipient dentary condyle and squamosal glenoid and the jaws articulate solely using a plesiomorphic quadrate-articular joint. We postulate that the jaw joint underwent marked evolutionary changes in probainognathian cynodonts. Some probainognathian clades independently acquired 'double' craniomandibular contacts, with mammaliaforms attaining a fully independent dentary-squamosal articulation with a conspicuous dentary condyle and squamosal glenoid in the Late Triassic. The dentary-squamosal contact, which is traditionally considered to be a typical mammalian feature, therefore evolved more than once and is more evolutionary labile than previously considered.

Mycoplasma hyopharyngis isolated from the joint of a weaner: A case report.

Background: Mycoplasma hyopharyngis is a commensal bacterium in the upper respiratory tract of swine. As it is recognized to be apathogenic, examinations regarding this species are scarce, compared to other swine mycoplasmas. However, in a few cases, M. hyopharyngis was detected in lesions of different organs. This report presents a case study in which M. hyopharyngis (along with other bacteria) was isolated from the joint of a pig showing lameness. Case presentation: A Hungarian farm was repopulated with 250 gilts and 1,700 finishers after undergoing a complete depopulation and disinfection. Two days later, cases of diarrhoea and septicaemia caused by Salmonella enterica serovar typhimurium were seen in the finishers. At the same time, following the first farrowing, swollen joints were observed in 21-25 days old piglets. Joint samples were collected, and isolation of Mycoplasma sp. and other bacteria was attempted. Analysis of the joint samples revealed the presence of Staphylococcus haemolyticus, Staphylococcus hyicus, Aerococcus viridans, Trueperella pyogenes, Streptococcus agalactiae and M. hyopharyngis. Conclusions: This is the second isolation of M. hyopharyngis from joints, which highlights the necessity of a better understanding the biology of this often-overlooked species, and its role in the progress of arthritis or other lesions.

How anatomy influences measurements of snakes.

Anatomy compromises the precision and accuracy of measurements made of the body length and head size of live snakes. Body measures (snout-vent length, SVL) incorporate many synovial intervertebral joints, each allowing flexion and limited extension and compression. Radiographs of the trunk in 14 phylogenetically diverse species in resting and stretched conditions combined with dissections and histological analysis of intervertebral joints show that the synovial nature of these joints underlies the variance in SVL measures. Similarly, the ubiquity and variety of viscoelastic tissues connecting mobile snout and jaw elements of alethinophidian snakes underlie variances in length and width measures of the head. For the overall size of the head and jaw apparatus, the part that can be most easily and relatively precisely measured for many snakes is the mandible because it has only one mobile joint. As to accuracy, the anatomy of intervertebral and cranial joints supports the hypothesis that in living snakes, the head and trunk have no exact size.

Unraveling the joints: a narrative review of osteoarthritis.

Osteoarthritis (OA) is a chronic and progressive degenerative disease that affects joint structures, such as the hips, knees, and hands, involving the articular cartilage, subchondral bone, ligaments, capsule, and synovium. OA is characterized by a progressive degeneration of the joint structures, resulting in pain and decreased quality of life. Local and systemic risk factors pave the way for OA development. Different phenotypes may be identified, but three main molecular mechanisms define the endotypes: the bone-driven endotype, the synovitis-driven endotype, and the cartilage-driven endotype. The hallmark of OA pathophysiology involves more than just mechanical degradation; it includes the release of pro-inflammatory mediators, such as interleukins and TNF-α, which elucidates the significant roles of metabolic syndrome, diabetes, and cellular senescence in its development. OA is distinguished by a clinical presentation that varies significantly between people and is marked by pain, stiffness, and functional impairments. The clinical course can be split into Pre-OA, Early OA, Evident OA, and End-Stage. Depending on the stage of the disease, OA diagnosis frequently necessitates a complex strategy that combines clinical evaluation to detect joint tenderness, range of motion, and joint swelling or abnormalities, medical history assessment, imaging modalities, and laboratory investigations. There is no known treatment for OA, and different therapies are usually evaluated based on the stage of the disease to minimize pain and stiffness while maintaining joint function. Treatments are divided into the reduction of modifiable risk factors, pharmacologic therapies, rehabilitation, complementary therapies, interventional pain procedures, and surgery. OA clinical heterogeneity underlines the importance of prevention, early diagnosis, and identifying the phenotype and endotype to tailor the treatment.

Muscle short-range stiffness behaves like a maxwell element, not a spring: Implications for joint stability.

INTRODUCTION: Muscles play a critical role in supporting joints during activities of daily living, owing, in part, to the phenomenon of short-range stiffness. Briefly, when an active muscle is lengthened, bound cross-bridges are stretched, yielding forces greater than what is predicted from the force length relationship. For this reason, short-range stiffness has been proposed as an attractive mechanism for providing joint stability. However, there has yet to be a forward dynamic simulation employing a cross-bridge model, that demonstrates this stabilizing role. Therefore, the purpose of this investigation was to test whether Huxley-type muscle elements, which exhibit short-range stiffness, can stabilize a joint while at constant activation. METHODS: We analyzed the stability of an inverted pendulum (moment of inertia: 2.7 kg m2) supported by Huxley-type muscle models that reproduce the short-range stiffness phenomenon. We calculated the muscle forces that would provide sufficient short-range stiffness to stabilize the system based in minimizing the potential energy. Simulations consisted of a 50 ms long, 5 Nm square-wave perturbation, with numerical simulations carried out in ArtiSynth. RESULTS: Despite the initial analysis predicting shared activity of antagonist and agonist muscles to maintain stable equilibrium, the inverted pendulum model was not stable, and did not maintain an upright posture even with fully activated muscles. DISCUSSION & CONCLUSION: Our simulations suggested that short-range stiffness cannot be solely responsible for joint stability, even for modest perturbations. We argue that short-range stiffness cannot achieve stability because its dynamics do not behave like a typical spring. Instead, an alternative conceptual model for short-range stiffness is that of a Maxwell element (spring and damper in series), which can be obtained as a first-order approximation to the Huxley model. We postulate that the damping that results from short-range stiffness slows down the mechanical response and allows the central nervous system time to react and stabilize the joint. We speculate that other mechanisms, like reflexes or residual force enhancement/depression, may also play a role in joint stability. Joint stability is due to a combination of factors, and further research is needed to fully understand this complex system.

[Advances in genetic research on Non-syndromic congenital joint synostosis].

Congenital joint synostosis (CJS) is a functional impairment resulting from failure in joint morphogenesis during embryonic development. Clinically, it may be classified as syndromic (sCJS) and non-syndromic (nsCJS) disorders. Common sCJS include chromosomal disorders such as Klinefelter syndrome and single-gene disorders like Apert/Pfeiffer/Crouzon syndromes, Holt-Oram syndrome, Ehlers-Danlos syndrome, and Radial-ulnar synostosis with thrombocytopenia, presenting with multiple system/organ anomalies. By contrast, nsCJS manifest with only joint abnormalities, affecting one or multiple joints. This review has focused on human nsCJS and its genetic etiology. To date, variants in seven genes (NOG, GDF5, FGF9, GDF6, FGF16, SMAD6, and MECOM) have been identified as causative factors for nsCJS. This review has focused on such genes and provided a comprehensive review for the clinical phenotypes, genetic patterns, common variants, and underlying mechanisms associated with nsCJS based on a literature review. In addition, it has also analyzed other candidate genes for nsCJS within the context of relevant signaling pathways involved in joint morphogenesis.

Integrin signalling in joint development, homeostasis and osteoarthritis.

Integrins are key regulators of cell-matrix interactions during joint development and joint tissue homeostasis, as well as in the development of osteoarthritis (OA). The signalling cascades initiated by the interactions of integrins with a complex network of extracellular matrix (ECM) components and intracellular adaptor proteins orchestrate cellular responses necessary for maintaining joint tissue integrity. Dysregulated integrin signalling, triggered by matrix degradation products such as matrikines, disrupts this delicate balance, tipping the scales towards an environment conducive to OA pathogenesis. The interplay between integrin signalling and growth factor pathways further underscores the multifaceted nature of OA. Moreover, emerging insights into the role of endocytic trafficking in regulating integrin signalling add a new layer of complexity to the understanding of OA development. To harness the therapeutic potential of targeting integrins for mitigation of OA, comprehensive understanding of their molecular mechanisms across joint tissues is imperative. Ultimately, deciphering the complexities of integrin signalling will advance the ability to treat OA and alleviate its global burden.

Undenatured type II collagen protects against collagen-induced arthritis by restoring gut-joint homeostasis and immunity.

Oral administration of harmless antigens can induce suppression of reactive immune responses, a process that capitalises on the ability of the gastrointestinal tract to tolerate exposure to food and commensal microbiome without triggering inflammatory responses. Repeating exposure to type II collagen induces oral tolerance and inhibits induction of arthritis, a chronic inflammatory joint condition. Although some mechanisms underlying oral tolerance are described, how dysregulation of gut immune networks impacts on inflammation of distant tissues like the joints is unclear. We used undenatured type II collagen in a prophylactic regime -7.33 mg/kg three times/week- to describe the mechanisms associated with protective oral immune-therapy (OIT) in gut and joint during experimental Collagen-Induced Arthritis (CIA). OIT reduced disease incidence to 50%, with reduced expression of IL-17 and IL-22 in the joints of asymptomatic mice. Moreover, whilst the gut tissue of arthritic mice shows substantial damage and activation of tissue-specific immune networks, oral administration of undenatured type II collagen protects against gut pathology in all mice, symptomatic and asymptomatic, rewiring IL-17/IL-22 networks. Furthermore, gut fucosylation and microbiome composition were also modulated. These results corroborate the relevance of the gut-joint axis in arthritis, showing novel regulatory mechanisms linked to therapeutic OIT in joint disease.