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BackgroundObesity influences the development of osteoarthritis via low-grade inflammation. Progression of local inflammation (= synovitis) increased with weight gain in overweight and obese women compared to stable weight. Synovitis could be associated with subcutaneous fat (SCF) around the knee. Purpose of the study was to investigate the effect of weight loss on synovitis progression and to assess whether SCF around the knee mediates the relationship between weight loss and synovitis progression.MethodsWe included 234 overweight and obese participants (body mass index [BMI] ≥ 25 kg/m2) from the Osteoarthritis Initiative (OAI) with > 10% weight loss (n = 117) or stable overweight (

Pain is one of the most debilitating symptoms of rheumatoid arthritis (RA), and yet remains poorly understood, especially when pain occurs in the absence of synovitis. Without active inflammation, experts most often attribute joint pain to central nervous system dysfunction. However, advances in the past 5 years in both immunology and neuroscience research suggest that chronic pain in RA is also driven by a variety of abnormal interactions between peripheral neurons and mediators produced by resident cells in the local joint environment. In this Review, we discuss these novel insights from an interdisciplinary neuro-immune perspective. We outline a potential working model for the peripheral drivers of pain in RA, which includes autoantibodies, resident immune and mesenchymal cells and their interactions with different subtypes of peripheral sensory neurons. We also offer suggestions for how future collaborative research could be designed to accelerate analgesic drug development. Emerging data suggest that resident cells and locally produced mediators interact with nerves in the joint to promote pain in rheumatoid arthritis. This Review discusses the potential neuro–immune–stromal interactions promoting joint pain and highlights the need for an interdisciplinary approach to therapeutic development. Key points: With the advent of biologic drugs bringing ever-improving disease control, pain is emerging as one of the most important remaining symptoms in rheumatoid arthritis. Pain mechanisms in rheumatoid arthritis are still not fully understood, especially when pain is uncoupled from joint inflammation. Emerging evidence implicates not only immune cells and cytokines but also autoantibodies and mesenchymal cells in arthritis-induced neuronal hyperactivity. Efforts towards large collaborative and interdisciplinary consortia to address specific questions are promising and valuable in accelerating our understanding of pain in rheumatoid arthritis. Recognizing pain as a distinct and essential clinical outcome in addition to disease activity and tissue damage is vital. [ABSTRACT FROM AUTHOR]

Objectives: Detection of synovitis is essential for assessing the activity and predicting the prognosis of rheumatoid arthritis (RA). The aim of this study was to investigate the diagnostic performance of superb microvascular imaging (SMI) in RA patients with high, moderate, and low activity. Methods: One hundred four patients with active RA were selected from the hospital between May 2022 and August 2023. The study observed the correlation between bone erosion of the carpal joint, joint cavity effusion, thickness of synovial hyperplasia of the carpal joint, positivity rate of synovial blood vessels, and their semiquantitative scores with the clinical disease activity of RA using SMI examination. Results: The detection of synovial hyperplasia thickness and joint effusion in the high-activity group was higher than that in the low-activity group, and the difference was statistically significant (P < 0.05). The quantitative SMI test demonstrated that the synovial blood flow grading and semiquantitative grade increased gradually with activity level (P<0.05). During the high, moderate, and low-activity groups, the vascular index (VI) value of the hyperplastic synovial membrane decreased gradually, showing statistical significance both between and within the groups (P<0.05). Conclusion: SMI technology exhibited high sensitivity and accuracy in assessing disease activity in RA. It holds significant clinical application value as a reliable auxiliary tool for assessing disease activity in RA and treatment. Key Points • Super micro-vascular imaging (SMI) demonstrated higher detection rates of microvessels in RA patients with high disease activity compared to those with low activity, showing statistical significance. • The quantitative SMI test revealed a clear correlation between synovial blood flow grading and disease activity levels in RA patients, highlighting the potential of SMI as a valuable tool for disease activity and treatment of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

This review provides an overview of SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis), a rare autoinflammatory disease that primarily affects bones, skin, and joints. We conducted a search on Medline/PubMed using keywords such as SAPHO syndrome, chronic recurrent multifocal osteitis/osteomyelitis, and related terms. SAPHO syndrome is rare, with a reported frequency of 1 in 10,000 in the Caucasian population. However, the actual incidence of SAPHO syndrome is unknown, and the incidence of the disease is likely higher. The pathogenesis of SAPHO syndrome remains incompletely understood. Current evidence suggests that SAPHO results from a complex interplay between immune dysregulation, genetic susceptibility, and environmental factors. It's not clear if SAPHO syndrome is an autoimmune disease or an autoinflammatory disease, but current evidence suggests that it's more likely an autoinflammatory disease because of things like neutrophil hyperactivity, fewer natural killer (NK) cells, high levels of interleukin (IL)-1, and a good response to treatments that block IL-1. Osteo-articular (OA) involvement is a key clinical feature of SAPHO. It affects the anterior chest wall, axial skeleton, peripheral joints, mandible, long bones of the extremities, and pelvis. Dermatological involvement is a common target in SAPHO, with lesions observed in 60–90% of cases. Common skin lesions include psoriasis and acne, with hidradenitis suppurativa and neutrophilic dermatoses being less commonly seen. Other clinical findings include constitutional symptoms caused by systemic inflammation, such as fever, weight loss, and fatigue. There is no specific laboratory finding for SAPHO syndrome. However, during active disease, there may be an increase in positive acute phase markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement levels, mild leukocytosis, and thrombocytosis. Diagnosis is crucial for SAPHO syndrome, which lacks a specific diagnostic finding and is often underrecognized. A comprehensive evaluation of a patient's medical history and physical examination is crucial. Treatment options include non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional and synthetic disease-modifying agents (cDMARDs and sDMARDs), biological therapies, bisphosphonates, and antibiotics. Biological treatments have emerged as a viable alternative for SAPHO patients who do not respond to conventional treatments. [ABSTRACT FROM AUTHOR]

BACKGROUND: Dockworkers are exposed to physical overloads that can contribute to the development of musculoskeletal disorders, leading to functional disability and absenteeism. OBJECTIVE: to map, critically appraise, and synthesize the available evidence on the prevalence of musculoskeletal diseases associated with port occupational activities. METHODS: A comprehensive search was conducted in structured and unstructured databases in August 2023, with no date or language restriction, to identify observational studies evaluating the prevalence of musculoskeletal disorders in dockworkers' occupational activity. The risk of bias was assessed using validated tools based on the included study designs. Data from studies were pooled in meta-analyses. The certainty of the evidence was assessed using the GRADE approach. RESULTS: We identified 12 analytical cross-sectional studies involving 7821 participants in ports of five countries. Most studies (75%) had a moderate methodological quality according to the Joanna Briggs Institute tool. Considering the overall worker categories and any musculoskeletal disorders, the meta-analysis showed a prevalence of 58% (95% Confidence Interval [95% CI] 37% to 78%), with degenerative spinal diseases 42% (95% CI –0.6% to 91%) and low back pain 36% (95% CI 21% to 50%) being the most prevalent conditions. Symptoms were predominantly in foremen and stevedores. The certainty of the evidence was very low. CONCLUSIONS: Musculoskeletal disorders seem prevalent among dockworkers, mainly degenerative spinal diseases and low back pain. Studies with greater methodological consistency are still needed to validate these hypotheses and assist in decision-making for implementing preventive and informational policies in maritime port management organizations. PROSPERO registry CRD42021257677. [ABSTRACT FROM AUTHOR]

Objectives: To identify an optimal pediatric musculoskeletal ultrasound (MSUS) protocol for the detection of knee arthritis in patients with juvenile idiopathic arthritis (JIA) including a comparison with existing protocols. Secondary aims were to correlate MSUS-identified B-Mode (BM) and Power Doppler-Mode (PD) synovitis with clinical findings. Methods: Consecutive JIA patients with confirmed knee arthritis after clinical examination underwent a thorough MSUS study protocol which included views identified and consented by the Pediatric Rheumatology european Society (PReS) Imaging Working Party for the detection of synovitis. In total eight views including measurement of the suprapatellar recess were included. Scoring of synovitis followed the pediatric OMERACT criteria (BM and PD severity grading 0 to 3). Interobserver reliability of BM and PD was tested before study begin. Previously published MSUS protocols for knee synovitis were also identified from the literature and their scan protocols compared to identify differences in sensitivity for synovitis according to the number and specific type of views included. Finally, a clinically applicable MSUS protocol for knee synovitis could be proposed. Results: In 114 patients with clinically active knee inflammation, BM positivity (grading ≥ 1) was most frequently detected in the suprapatellar longitudinal and transverse scans performed in any positioning (frequency 97–99% in suprapatellar longitudinal in 30° or neutral respectively). PD positivity was however higher in these views performed in 30° flexion compared to neutral. Intrasynovial PD positivity (grading ≥ 1) was most frequently detected in the lateral parapatellar (69%, sensitivity 0.68, specificity 0.98), medial parapatellar (frequency 67%, sensitivity 0.67, specificity 1.0), the longitudinal lateral (68%, sensitivity 0.67, specificity 0.98) and suprapatellar transverse in 30° (frequency 64%, sensitivity 0.64, specificity 1.0). A combination of five views was the most sensitive for BM and PD synovitis. The suprapatellar recess size was analyzed by age and gender. For each group, the recess was wider in knees with arthritis than without (p < 0.001). Interobserver reliability of BM and PD positivity showed 85% agreement, with kappa 0.74 (very good). Three published studies with knee synovitis MSUS protocols were identified, which included a range of 1–3 views. Evaluation of the sensitivity of positive PD findings of each of these protocols reached a range of 53–83%; the highest sensitivity (91%) was achieved with the 5 views as identified by this study. These five views were therefore combined to form the Pediatric Internationally agreed Ultrasound (PIUS) knee protocol. Conclusion: BM and PD positivity reliably correlated with the identification of pathological findings in knees of patients with JIA. From an internationally agreed protocol of eight images, a combination of five showed the greatest sensitivity for synovitis. This protocol, termed 'PIUS-Knee' performed well when compared to existing protocols. Key messages: • Synovitis detected using B-Mode and Doppler-Mode Musculoskeletal Ultrasound (MSUS) correlated strongly with clinical examination findings. • A combination of five specific MSUS views achieved the most sensitive B-Mode and Doppler-Mode protocol for knee synovitis. • This optimized knee examination ultrasound protocol termed PIUS-Knee (Pediatric Internationally Agreed Ultrasound) has high sensitivity for detecting intrasynovial hypervascularity. [ABSTRACT FROM AUTHOR]

Introduction: Clinical remission is the main target in the management of patients with rheumatoid arthritis (RA). However, several authors found synovitis in patients with RA in clinical remission at ultrasonography (US). Upadacitinib is a selective Janus kinase 1 inhibitor that achieved significantly higher remission rates than adalimumab and abatacept in patients with RA. Here we present the 24-week data of the UPAdacitinib Rheumatoid Arthritis REmission UltraSonography (UPARAREMUS) study. Methods: This is a longitudinal multicenter observational study, enrolling bio-naïve and bio-inadequate responder patients affected by RA. The primary endpoint was the proportion of patients achieving both clinical and US remission at week 24. The proportion of patients achieving clinical remission with different composite indexes at week 12 and 24 was also evaluated. US of four target joints (wrists and second metacarpophalangeal bilaterally) was performed at baseline and weeks 12/24, and US remission was defined as the absence of power Doppler (PD) signal ≥ 2 in one target joint, or PD ≥ 1 in two target joints. Results: After 12 weeks and 24 weeks, 40% and 63.6% of patients achieved US plus clinical remission. The following parameters were associated with US plus clinical remission: being bio-naïve and having a shorter disease duration, although at multivariate analysis significant odds ratio (OR) was found only for being bio-naïve. Conclusions: UPARAREMUS is the first study evaluating the efficacy of upadacitinib in reaching both clinical and US remission in patients with RA. At 24 weeks, 63.6% of patients reached the primary endpoint, the only baseline associated parameter was being bio-naïve. [ABSTRACT FROM AUTHOR]

Background and Aims: Plain film radiography is the first imaging modality in the detection of most foreign bodies. However, it is not sensitive for detection of radiolucent objects such as organic material including plant thorns. Case report: Herein, we present the case of a 19-year-old male patient, presenting with an 8-month history of right knee pain and laxity, whose radiographic appearance mimicked that of pigmented villonodular synovitis (PVNS) but was found to have a retained neglected plant thorn in his knee. Upon ultrasound evaluation for image-guided biopsy to confirm the provisional diagnosis of PVNS, he was found to have a retained neglected plant thorn in his knee. Discussion: Plant thorn injuries can present as knee synovitis, as in our case, and should be kept in the differential diagnosis. An ultrasound-guided removal is possible and is a useful minimally invasive procedure. [ABSTRACT FROM AUTHOR]

Synovial pathology has been linked to osteoarthritis (OA) pain in patients. Microscopic grading systems for synovial changes in human OA have been described, but a standardized approach for murine models of OA is needed. We sought to develop a reproducible approach and set of minimum recommendations for reporting of synovial histopathology in mouse models of OA. Coronal and sagittal sections from male mouse knee joints subjected to destabilization of medial meniscus (DMM) or partial meniscectomy (PMX) were collected as part of other studies. Stains included Hematoxylin and Eosin (H&E), Toluidine Blue (T-Blue), and Safranin O/Fast Green (Saf-O). Four blinded readers graded pathological features (hyperplasia, cellularity, and fibrosis) at specific anatomic locations. Inter-reader agreement of each feature score was determined. There was acceptable to very good agreement when using 3–4 individual readers. After DMM and PMX, expected medial predominant changes in hyperplasia and cellularity were observed, with fibrosis noted at 12 weeks post -PMX. Synovial changes were consistent from section to section in the mid-joint area. When comparing stains, H&E and T-blue resulted in better agreement compared to Saf-O stain. To account for the pathologic and anatomic variability in synovial pathology and allow for a more standardized evaluation that can be compared across studies, we recommend evaluating a minimum set of 3 pathological features at standardized anatomic areas. Further, we suggest reporting individual feature scores separately before relying on a single summed "synovitis" score. H&E or T-blue are preferred, inter-reader agreement for each feature should be considered. [ABSTRACT FROM AUTHOR]

To confirm the protective mechanism of genistein on osteoarthritis (OA). Firstly, we constructed an anterior cruciate ligament transection (ACLT) rat model and administered two doses of genistein via gavage. The effects of the drug on cartilage damage repair and synovitis in OA rats were evaluated through pain-related behavioral assessments, pathological staining, detection of inflammatory factors, and western blot analysis. Secondly, we constructed IL-1-induced chondrocytes and synovial fibroblast models, co-incubated them with genistein, and evaluated the protective effects of genistein on both types of cells through cell apoptosis and cytoskeleton staining. To verify the role of this pathway, we applied the GSK3β inhibitor TWS119 and the Wnt/β-catenin inhibitor XAV939 to ACLT rats and two types of cells to analyze the potential mechanism of genistein's action on OA. Our results confirmed the protective effect of genistein on joint cartilage injury in ACLT rats and its alleviating effect on synovitis. The results of cell experiments showed that genistein can protect IL-1β-induced chondrocytes and synovial fibroblasts, inhibit IL-1β-induced cell apoptosis, increase the fluorescence intensity of F-actin, and inhibit inflammatory response. The results of in vivo and in vitro mechanism studies indicated that TWS119 and XAV939 can attenuate the protective effects of genistein on OA rats and IL-1-induced cell damage. Our research confirmed that genistein may be an effective drug for treating osteoarthritis. Furthermore, we discussed and confirmed that the GSK3β/Wnt/β-catenin axis serves as a downstream signaling pathway of genistein, providing theoretical support for its application. [ABSTRACT FROM AUTHOR]

The enthesitis hypothesis posits that enthesitis is a primary lesion and that inflammation at the enthesis initiates the musculoskeletal symptoms of psoriatic arthritis (PsA) and spondyloarthropathies (SpA). The hypothesis suggested that inflamed entheseal tissue near the synovium could trigger cytokine-mediated synovitis, that enthesis bone anchorage could explain osteitis, and that the location of entheses at the soft tissue interface could explain dactylitis. Advances in imaging techniques that allow better visualization of enthesitis lesions and the development of animal models have allowed evolution of the concept of enthesitis as a central mechanistic driver of musculoskeletal symptoms in PsA and SpA. A debate between Drs. Dennis McGonagle and Bruce Kirkham at the Group for Research on Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting discussed the data supporting and refuting this hypothesis in PsA and SpA, respectively. The major points of this debate are summarized in this article. [ABSTRACT FROM AUTHOR]

The sensitivity of ultrasound (US) to detect, characterize, and monitor the relevant pathologies of psoriatic arthritis (PsA), including synovitis, enthesitis, tenosynovitis, and dactylitis, has made it an attractive tool for informing clinical decisions. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) US working group ran 2 sessions during the annual GRAPPA meeting held in July 2023 in Dublin, Ireland. During the first workshop, the group presented 2 topics, followed by a live demonstration and a group discussion. The 2 topics were (1) an overview of the Diagnostic Ultrasound Enthesitis Tool (DUET) enthesitis scoring methodology, and (2) small hand-held probes—will the promise deliver? The live demonstration that followed compared the performance of 2 hand-held US (HHUS) devices vs a console US machine in patients with PsA, and the interactive group discussion considered gaps in the literature and future research suggestions relating to HHUS and its application in psoriatic disease. During the second session, the US working group provided further updates regarding the GRAPPA US studies currently underway or recently completed. [ABSTRACT FROM AUTHOR]

Purpose: A classification-based segmentation method is proposed to quantify synovium in rheumatoid arthritis (RA) patients using a deep learning (DL) method based on time-intensity curve (TIC) analysis in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Materials and methods: This retrospective study analyzed a hand MR dataset of 28 RA patients (six males, mean age 53.7 years). A researcher, under expert guidance, used in-house software to delineate regions of interest (ROIs) for hand muscles, bones, and synovitis, generating a dataset with 27,255 pixels with corresponding TICs (muscle: 11,413, bone: 8502, synovitis: 7340). One experienced musculoskeletal radiologist performed ground truth segmentation of enhanced pannus in the joint bounding box on the 10th DCE phase, or around 5 min after contrast injection. Data preprocessing included median filtering for noise reduction, phase-only correlation algorithm for motion correction, and contrast-limited adaptive histogram equalization for improved image contrast and noise suppression. TIC intensity values were normalized using zero-mean normalization. A DL model with dilated causal convolution and SELU activation function was developed for enhanced pannus segmentation, tested using leave-one-out cross-validation. Results: 407 joint bounding boxes were manually segmented, with 129 synovitis masks. On the pixel-based level, the DL model achieved sensitivity of 85%, specificity of 98%, accuracy of 99% and precision of 84% for enhanced pannus segmentation, with a mean Dice score of 0.73. The false-positive rate for predicting cases without synovitis was 0.8%. DL-measured enhanced pannus volume strongly correlated with ground truth at both pixel-based (r = 0.87, p < 0.001) and patient-based levels (r = 0.84, p < 0.001). Bland–Altman analysis showed the mean difference for hand joints at the pixel-based and patient-based levels were −9.46 mm3 and −50.87 mm3, respectively. Conclusion: Our DL-based DCE-MRI TIC shape analysis has the potential for automatic segmentation and quantification of enhanced synovium in the hands of RA patients. [ABSTRACT FROM AUTHOR]

Background: The uncultured adipose-derived stromal vascular fraction (SVF), consisting of adipose-derived stromal cells (ADSCs), M2 macrophages (M2Φ) and others, has shown therapeutic potential against osteoarthritis (OA), however, the mechanisms underlying its therapeutic effects remain unclear. Therefore, this study investigated the effects of the SVF on OA in a human-immunodeficient rat xenotransplantation model. Methods: OA model was induced in the knees of female immunodeficient rats by destabilization of the medial meniscus. Immediately after the surgery, human SVF (1 × 105), ADSCs (1 × 104), or phosphate buffered saline as a control group were transplanted into the knees. At 4 and 8 weeks postoperatively, OA progression and synovitis were analyzed by macroscopic and histological analyses, and the expression of collagen II, SOX9, MMP-13, ADAMTS-5, F4/80, CD86 (M1), CD163 (M2), and human nuclear antigen (hNA) were evaluated immunohistochemically. In vitro, flow cytometry was performed to collect CD163-positive cells as M2Φ from the SVF. Chondrocyte pellets (1 × 105) were co-cultured with SVF (1 × 105), M2Φ (1 × 104), and ADSCs (1 × 104) or alone as a control group, and the pellet size was compared. TGF-β, IL-10 and MMP-13 concentrations in the medium were evaluated using enzyme-linked immunosorbent assay. Results: In comparison with the control and ADSC groups, the SVF group showed significantly slower OA progression and less synovitis with higher expression of collagen II and SOX9, lower expression of MMP-13 and ADAMTS-5, and lower F4/80 and M1/M2 ratio in the synovium. Only the SVF group showed partial expression of hNA-, CD163-, and F4/80-positive cells in the rat synovium. In vitro, the SVF, M2Φ, ADSC and control groups, in that order, showed larger pellet sizes, higher TGF-β and IL-10, and lower MMP-13 concentrations. Conclusions: The M2Φ in the transplanted SVF directly affected recipient tissue, enhancing the secretion of growth factors and chondrocyte-protecting cytokines, and partially improving chondrocytes and joint homeostasis. These findings indicate that the SVF is as an effective option for regenerative therapy for OA, with mechanisms different from those of ADSCs. [ABSTRACT FROM AUTHOR]

Primary osteoarthritis (OA) is a prevalent degenerative joint disease that mostly affects the knee joint. It is a condition that occurs around the world. Because of the aging population and the increase in obesity prevalence, the incidence of primary OA is increasing each year. Joint replacement can completely subside the pain and minimize movement disorders caused by advanced OA, while nonsteroidal drugs and injection of sodium hyaluronate into the joint cavity can only partially relieve the pain; hence, it is critical to search for new methods to treat OA. Increasing lines of evidence show that primary OA is a chronic inflammatory disorder, with synovial inflammation as the main characteristic. Macrophages, as one of the immune cells, can be polarized to produce M1 (proinflammatory) and M2 (anti-inflammatory) types during synovial inflammation in OA. Following polarization, macrophages do not come in direct contact with chondrocytes; however, they affect chondrocyte metabolism through paracrine production of a significant quantity of inflammatory cytokines, matrix metalloproteinases, and growth factors and thus participate in inducing joint pain, cartilage injury, angiogenesis, and osteophyte formation. The main pathways that influence the polarization of macrophages are the Toll-like receptor and NF-κB pathways. The study of how macrophage polarization affects OA disease progression has gradually become one of the approaches to prevent and treat OA. Experimental studies have found that the treatment of macrophage polarization in primary OA can effectively relieve synovial inflammation and reduce cartilage damage. The present article summarizes the influence of inflammatory factors secreted by macrophages after polarization on OA disease progression, the main signaling pathways that induce macrophage differentiation, and the role of different polarized types of macrophages in OA; thus, providing a reference for preventing and treating primary OA. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is defined by articular cartilage degeneration, synovial membrane inflammation, and abnormal bone remodeling. Recent study has discovered that OA development is linked to an aberrant epigenetic modification of OA‐related genes. Our previous research showed that DNA demethylation in ADAMTS‐5 promoter region had a substantial impact on ADAMTS‐5 expression in the mouse OA model. This process facilitated the binding of Spi‐1 to ADAMTS‐5 promoter. While alterations in histone methylation have been documented during embryonic development and cancer development, there is a paucity of data on the change in OA pathogenesis. Even no data have been reported on the role of histone modifications in ADAMTS‐5 activation in OA. Following our previous study on the role of DNA methylation, we aimed to examine the contribution of histone H3K9 dimethylation in ADAMTS‐5 activation in OA. Additionally, we aimed to elucidate the molecular mechanisms underlying the cooperative interaction between DNA methylation and histone H3K9 dimethylation. The potential for anti‐OA intervention therapy which is based on modulating histone H3K9 dimethylation is also explored. We demonstrated that a reduction in histone H3K9 dimethylation, along with DNA demethylation of the Spi‐1 binding site, had a role in ADAMTS‐5 activation in the articular cartilage of OA mice. Significantly, the conditional deletion of histone demethylase to be identified as lysine‐specific demethylase 1 (LSD1) in articular cartilage could alleviate the degenerative features of OA mice. Our study demonstrates the direct impact of histone H3K9 dimethylation on gene expression, which in turn contributes to OA development. This research enhances our understanding of the underlying causes of OA. [ABSTRACT FROM AUTHOR]

Introduction Aim Method Results Conclusion The term ‘chronic inflammatory arthritis’ (IA) can be used to define a group of heterogeneous diseases in which inflammation of the synovium is the common feature while having different pathogenesis and clinical outcomes. This condition can be found in osteoarthritis (OA), rheumatoid arthritis (RA), and hemophilic arthropathy (HA).The objective is to try to highlight similarities and differences in the three pathological conditions and understand both molecular and physiological mechanisms.We have carried out a systematic review of the available literature following the guidelines Preferred Reporting Items for Systematic Reviews and Meta‐analysis (PRISMA).By comparing the data in the literature on OA, RA, and HA we have shown that the three pathologies differ in initial etiology but they motivate the same molecular pathways.In this review we highlighted the similarities and differences between these diseases, creating ideas for future studies both in vivo and in vitro to develop new therapeutic agents and suggest possible biomarkers to follow the evolution and severity of the disease. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovitis, degradation of articular cartilage, and bone destruction. Fibroblast-like synoviocytes (FLS) play a central role in RA, producing a significant amount of inflammatory mediators such as tumor necrosis factor(TNF)-a and IL-6, which promote inflammatory responses within the joints. Moreover, FLS exhibit tumor-like behavior, including aggressive proliferation and enhanced anti-apoptotic capabilities, which collectively drive chronic inflammation and joint damage in RA. TNF is a major pro-inflammatory cytokine that mediates a series of signaling pathways through its receptor TNFR1, including NF-κB and MAPK pathways, which are crucial for inflammation and cell survival in RA. The abnormal proliferation and anti-apoptotic characteristics of FLS in RA may result from dysregulation in TNFmediated cell death pathways such as apoptosis and necroptosis. Ubiquitination is a critical post-translational modification regulating these signaling pathways. E3 ubiquitin ligases, such as cIAP1/2, promote the ubiquitination and degradation of target proteins within the TNF receptor complex, modulating the signaling proteins. The high expression of the BIRC3 gene and its encoded protein, cIAP2, in RA regulates various cellular processes, including apoptosis, inflammatory signaling, immune response, MAPK signaling, and cell proliferation, thereby promoting FLS survival and inflammatory responses. Inhibiting BIRC3 expression can reduce the secretion of inflammatory cytokines by RA-FLS under both basal and inflammatory conditions and inhibit their proliferation. Although BIRC3 inhibitors show potential in RA treatment, their possible side effects must be carefully considered. Further research into the specific mechanisms of BIRC3, including its roles in cell signaling, apoptosis regulation, and immune evasion, is crucial for identifying new therapeutic targets and strategies. [ABSTRACT FROM AUTHOR]

Background: Transient synovitis of the hip is the most common cause of limping in paediatric emergency departments. There is no consensus regarding routine follow-up after hip synovitis among children, and there are no standardized criteria for selecting cases that warrant follow-up due to persistent or recurring symptoms to rule out the possibility of Legg-Calvé-Perthes disease. Delayed treatment of Legg-Calvé-Perthes disease may increase the risk of developing early secondary coxarthrosis. Understanding the prevalence of Legg-Calvé-Perthes disease among paediatric patients with transient synovitis of the hip is of paramount importance and could empower both parents and paediatricians to make well-informed decisions when selecting follow-up care for children, thus ensuring that no cases of Legg-Calvé-Perthes disease are missed among diagnosis paediatric patients with transient synovitis of the hip. The aim of this review was to estimate the prevalence of Legg-Calvé-Perthes disease among paediatric patients with transient synovitis of the hip. Methods: This study was conducted in strict accordance with the PRISMA guidelines and was registered with PROSPERO. The PubMed, Embase, and Cochrane Library databases were comprehensively searched up to July 2024 to identify relevant studies. The inclusion criteria were as follows: patients diagnosed with transient synovitis of the hip; patients aged up to 18 years; and studies with a minimum of 10 cases of paediatric transient synovitis of the hip. To pool the prevalence rates from individual studies, we utilized a random-effects meta-analysis. To assess the quality of the included studies in detail, we employed the Joanna Briggs Institute's quality assessment checklist. Results: A total of 19 studies were ultimately included for the final analysis, with 2,617 paediatric cases of transient synovitis of the hip. The results of meta-analysis revealed that the pooled prevalence estimate of Legg-Calvé-Perthes disease among all paediatric patients with transient synovitis of the hip was 2.7% (95% CI 1.4–5.1). Significant heterogeneity was observed across the studies included in this analysis (I2 = 79.990%; P = 0.000). The pooled prevalence estimate of Legg-Calvé-Perthes disease among paediatric patients with recurrent or persistent transient synovitis of the hip was 36.3% (95% CI 21.6–54.2). Significant heterogeneity was also observed across the studies included in this analysis (I2 = 51.519%; P = 0.036). Furthermore, the follow-up period varied from 6 weeks to 24 months. The primary diagnostic imaging modality utilized for identifying Perthes disease was X-ray. Conclusion: Our study revealed that among paediatric patients with transient synovitis of the hip, routine X-ray follow-up of the hips after 6 weeks to rule out Legg-Calvé-Perthes disease is warranted only in patients who exhibit persistent or recurrent symptoms. [ABSTRACT FROM AUTHOR]

Musculoskeletal ultrasound (MSUS) is a powerful tool of major importance in rheumatology. MSUS is ideally suited for the evaluation of pediatric patients because it is a safe technique with a high patient acceptability, it does not require sedation, and it is excellent for exploring multiple joints. It is also the most operator-dependent imaging modality, and assessing joints in patients with juvenile idiopathic arthritis (JIA) is particularly challenging due to the unique features of the growing skeleton. Years ago, MSUS was already extensively used to manage rheumatoid arthritis (RA), which allowed pediatric rheumatologists to apply the knowledge generated in adult studies. It was a good starting point to study the joints of healthy children and JIA patients. Luckily, there is increasing evidence regarding the possibilities of MSUS in the management of JIA patients, with recent definitions for synovitis, descriptions of the sonographic features of joints in healthy children, and a better understanding of the role of subclinical synovitis. This review highlights the differences in normality and in pathological findings between children and adults assessed by MSUS. Specifically, this provides a summary of the current information on characteristics, scores, and definitions that are frequently different between JIA and RA patients. Despite the existence of several unresolved questions in the field, the value that MSUS adds to clinical examination in JIA has already been demonstrated, and we believe that MSUS may be included in the near future in treatment to target strategies. [ABSTRACT FROM AUTHOR]

Dactylitis is a clinical concept that corresponds to the swelling of the whole finger or toe giving a sausage appearance. Although it can be observed in different diseases, it is a distinctive clinical feature of psoriatic arthritis and is associated with a poor prognosis. Ultrasound has made it possible to improve our understanding of the pathogenesis of psoriatic arthritis dactylitis, identifying associated structural alterations, namely, flexor tenosynovitis, subcutaneous tissue edema, pulley inflammation with thickening and intra-pulley Doppler signals, extensor paratenonitis, synovitis, pericapsular bone formation, and flexor enthesitis. Given its complexity, a consensus has yet to be reached on an ultrasound-based definition of dactylitis. In addition, enthesitis is one of the characteristic features of spondyloartritis. Enthesitis, like dactylitis, is among the clinical manifestations in the Assessment of SpondyloArthritis international Society classification criteria for both axial and peripheral spondyloartritis and is a key feature for classifying psoriatic arthritis with the Classification criteria for Psoriatic Arthritis criteria. Ultrasonography is a very useful tool for exploring the enthesis. We have a good sonographic definition, although ultrasound findings do not always allow us to differentiate between mechanical or inflammatory lesions. Elementary lesions that characterize enthesopathy are hypoechogenicity at the enthesis, thickened enthesis, calci ficat ion/e nthes ophyt e at enthesis, erosion at enthesis, and Doppler signal at enthesis. Different composite indices have been proposed in order to classify spond yloar throp athie s. This article reviews the evaluation of dactylitis and enthesitis from the sonographic perspective. [ABSTRACT FROM AUTHOR]

Objectives To introduce and evaluate a simple method for assessing joint inflammation and structural damage on whole-body MRI (WBMRI) in juvenile idiopathic arthritis (JIA), which is usable in clinical practice. Methods The proposed system utilizes post-contrast Dixon WBMRI scans. Joints are assessed for synovitis (grade 0–2) and structural damage (present/absent) at 81 sites. The synovitis grading is based on features including above-normal intensity synovial enhancement, synovial hypertrophy, joint effusion, subarticular bone marrow oedema and peri-articular soft tissue oedema. This system was evaluated in a prospective study of 60 young people (47 patients with JIA and 13 controls with non-inflammatory musculoskeletal pain) who underwent a WBMRI. Three readers (blinded to diagnosis) independently reviewed all images and re-reviewed 20 individual scans. The intra- and inter-reader overall agreement (OA) and the intra- and inter-reader Gwet's agreement coefficients 2 (GAC2) were measured for the detection of a) participants with ≥1 joint with inflammation or structural damage and b) joint inflammation or structural damage for each joint. Results The inter-reader OA for detecting patients with ≥1 joint with inflammation, defined as grade 2 synovitis (G2), and ≥1 joint with structural damage were 80% and 73%, respectively. The intra-reader OA for readers 1–3 was 80–90% and 75–90%, respectively. The inter-reader OA and GAC2 for joint inflammation (G2) at each joint were both ≥85% for all joints but were lower if grade 1 synovitis was included as positive. Conclusion The intra- and inter-reader agreements of this WBMRI assessment system are adequate for assessing objective joint inflammation and damage in JIA. [ABSTRACT FROM AUTHOR]

Objectives To assess the frequency of joint inflammation detected by whole-body MRI (WBMRI) in young people (YP) with JIA and controls, and to determine the relationship between WBMRI-detected inflammation and clinical findings. Methods YP aged 14–24 years, with JIA (patients) or arthralgia without JIA (controls), recruited from one centre, underwent a WBMRI scan after formal clinical assessment. Consensus between at least two of the three independent radiologists was required to define inflammation and damage on WBMRI, according to predefined criteria. YP with JIA were deemed clinically active as per accepted definitions. The proportions of YP with positive WBMRI scans for joint inflammation (one or more inflamed joint) as well as serum biomarkers were compared between active vs inactive JIA patients and controls. Results Forty-seven YP with JIA (25 active and 22 inactive patients) and 13 controls were included. WBMRI detected joint inflammation in 60% (28/47) of patients with JIA vs 15% (2/13) of controls (difference: 44%, 95% CI 20%, 68%). More active than inactive JIA patients had WBMRI-detected inflammation [76% (19/25) vs 41% (9/22), difference: 35% (95% CI 9%, 62%)], and this was associated with a specific biomarker signature. WBMRI identified inflammation in one or more clinically inactive joint in 23/47 (49%) patients (14/25 active vs 9/22 inactive JIA patients). Conclusions WBMRI's validity in joint assessment was demonstrated by the higher frequency of inflammation in JIA patients vs controls, and in active vs inactive JIA patients. WBMRI found unsuspected joint inflammation in 49% YP with JIA, which needs further investigation of potential clinical implications. [ABSTRACT FROM AUTHOR]

Background: Posttraumatic osteoarthritis (PTOA) arises secondarily to joint trauma and is driven by catabolic inflammatory pathways. Alpha-2-macroglobulin (α2M) is a naturally occurring proteinase inhibitor found in human serum and synovial fluid that binds proteases as well as proinflammatory cytokines involved in the pathogenesis of PTOA. Purpose: (1) To investigate the therapeutic potential of intra-articular α2M injections during the acute stages of PTOA by inhibiting inflammatory pathways driven by the cytokines expressed by the synovium in a large preclinical Yucatan minipig model and (2) to determine if 3 intra-articular α2M injections have greater chondroprotective effects compared with 1 intra-articular injection. Study Design: Controlled laboratory study. Methods: A total of 48 Yucatan minipigs were randomized into 4 groups (n = 12 each): (1) modified intra-articular drilling (mIAD) and saline (mIAD + saline), (2) mIAD and 1 intra-articular α2M injection (mIAD +α2M-1), (3) mIAD and 3 α2M injections (mIAD +α2M-3), and (4) sham control. Surgical hindlimbs were harvested at 15 weeks after surgery. Cartilage degeneration, synovial changes, inflammatory gene expression, and matrix metalloproteinase levels were evaluated. Gait asymmetry was measured before and after surgery using a pressure-sensing walkway system. Results: Macroscopic lesion areas and microscopic cartilage degeneration scores were lower in the mIAD +α2M-1 and mIAD +α2M-3 groups compared with the mIAD + saline group (P <.05) and similar to those in the sham group (P >.05). Synovial membrane scores of the mIAD +α2M-1 and mIAD +α2M-3 groups were lower than that of the mIAD + saline group (P <.05) and higher than that of the sham group (P <.05). Interleukin-1 beta, nuclear factor kappa B, and tumor necrosis factor alpha mRNA expression in the synovium and matrix metalloproteinase-1 levels in synovial fluid were significantly lower in the mIAD +α2M-1 and mIAD +α2M-3 groups compared with the mIAD + saline group (P <.05). No significant differences were observed between the mIAD +α2M-1 and mIAD +α2M-3 groups for all measured outcomes. There were early changes in gait (P <.05) between preoperative and postoperative time points for the mIAD + saline, mIAD +α2M-1, and mIAD +α2M-3 groups that normalized by 15 weeks. Conclusion: Animals receiving early α2M treatment exhibited less cartilage damage, milder synovitis, and lower inflammation compared with animals with no α2M treatment. These results exemplify the early anti-inflammatory effects of α2M and provide evidence that intra-articular α2M injections may slow the progression of PTOA. Clinical Relevance: In patients presenting with an acute joint injury, an early intervention with α2M may have the potential to reduce cartilage degeneration from catabolic pathways and delay the development of PTOA. [ABSTRACT FROM AUTHOR]

Intra-articular blood, iron and hemosiderin, hydroxyl radical cytokines, and neo-angiogenesis cause synovial inflammation, which leads to cartilage and joint damage. Platelet-rich plasma (PRP) inhibits most of the mediators that produce and maintain synovitis. We compile here our work showing the clinical effectiveness of intra-articular PRP injections and their potential role in stopping articular cartilage damage due to bleeding and its possible repair. A total of 116 joints, including knees (63%), elbows (19.8%), and ankles (17.2%), were treated with intra-articular injections of PRP. Moreover, we also show here the number of extracellular DNA traps (ETs) and the PRP effect in the synovial fluid of patients at the time of treatment and six months after. Clinically, it is demonstrated that PRP is effective in reducing bleeding episodes (p < 0.001) and pain (p < 0.0001) and improving the hemophilia joint health score (HJHS) (p < 0.001) at one year of follow-up. Furthermore, our results demonstrate that PRP inhibits ET formation in vitro and reconstitutes the immune system's cellular components in the synovial fluid of patients after treatment. We conclude that PRP can be considered an effective, safe, and easy treatment for hemophilic synovitis. [ABSTRACT FROM AUTHOR]

Foot and ankle disorders are common during pregnancy, driven by significant physiological changes including weight distribution, hormonal fluctuations, and fluid balance. These changes often result in conditions such as varicose veins, thrombophlebitis, deep vein thrombosis (DVT), edema, overpronation, ankle sprains, metatarsalgia, stress fractures, ligament tears, synovitis, tendon tears, tenosynovitis, paratenonitis, plantar fasciitis, and Morton's neuroma. This paper emphasizes the diagnostic utility of ultrasound for these conditions, given its safety, non-invasiveness, and real-time imaging capabilities without ionizing radiation. Ultrasound is particularly effective for diagnosing venous disorders like varicose veins and thrombophlebitis, leveraging Doppler ultrasound to assess vein structure and function. It is also instrumental in identifying DVT, detecting vein dilation, reflux, and thrombosis. For conditions such as edema, ultrasound helps differentiate physiological from pathological causes, ensuring accurate diagnosis and management. In cases of musculoskeletal issues like overpronation, ankle sprains, ligament tears, and tendon pathologies, ultrasound provides detailed images of soft tissues, allowing for precise diagnosis and effective treatment planning. It is equally useful for detecting metatarsalgia, plantar fasciitis, and Morton's neuroma, offering insights into soft tissue abnormalities and guiding therapeutic interventions. Ultrasound's role extends to diagnosing foreign bodies in the foot and ankle, where it demonstrates high sensitivity and specificity. The accessibility and cost-effectiveness of ultrasound make it an invaluable tool in various healthcare settings, ensuring timely and accurate diagnosis and management of foot and ankle disorders during pregnancy, ultimately enhancing patient outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical characteristics of patients who presented with concomitant carpal tunnel syndrome (CTS) at the initial diagnosis with rheumatoid arthritis (RA). Methods: We analyzed patients with newly diagnosed RA at a single institution between 2012 and 2021. Patient demographic and laboratory data, the 2010 ACR/EULAR classification criteria, and the duration from the initial visit to RA diagnosis were compared between RA patients with concomitant CTS (RA with CTS group) and those without CTS (RA without CTS group). Results: The study included 235 patients (157 females), of which 11 patients (4.7%) presented with CTS at the initial diagnosis with RA. In the RA with CTS group, the age was significantly higher (P = .033), all patients were female, and anti-cyclic citrullinated peptide antibody (ACPA) was negative, and the duration to RA diagnosis was longer than in the RA without CTS group. Among all RA with CTS patients, ultrasonography showed power Doppler signal-positive tenosynovitis in the carpal tunnel, which is not usually detected in idiopathic CTS. Conclusions: Patients with concomitant CTS at the initial diagnosis with RA were characterized by old age, female sex, and negative ACPA. Patients with symptoms of CTS should undergo ultrasonography for early diagnosis of RA. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetric polyarthritis. RA is routinely treated by various systemic drugs; on the other hand, administration of intra-articular corticosteroids or different types of synovectomies can be used in case of systemic medication's failure. Chemical, radio isotopic, and surgical synovectomies are being used as therapeutic options for chronic synovitis to improve joint function. Chemical synovectomy is not well tolerated, and the long-term response is relatively low. Surgical synovectomy has a better success rate, but it recommends higher expenses. In radiation synovectomy, radioactive labeled particles are applied directly in the articular cavity, followed by homogeneous distribution in joint. Next, the radioactive particles are transported in the depth of synovia and phagocytized by inflammatory cells. Finally, the radiation leads to fibrosis and sclerosis of formerly inflamed synovial membrane; thus, it stops the inflammation and reduces the symptoms. It has a success rate of 40–100% and its effect can be similar to surgical synovectomy. Materials and methods: Thirty-one patients with resistant monoarthritis of the knee were enrolled in this study. One millicurie of phosphorus-32 was injected into patients' knee via US guide. Saline was injected afterwards to prevent leakage. Direct pressure was performed after removing the needle and the knee was flexed slowly to ensure homogenous distribution and fixed with a splint for 1 to 2 weeks. Patients were followed up after 2 weeks, 1 month, 2 months, and 6 months. The following variables were assessed by the treating rheumatologist: patients' pain, joint tenderness, effusion, and ROM. At the time of injection and after the first week, patients were investigated for any complication including infection, necrosis, pain, and swelling. The effect of clinical characteristics and demographic data on existing complications and the changes of pain, joint tenderness, effusion, and ROM was assessed. Results: Thirty-one patients with the mean age of 54.5 ± 12.2 years and the mean disease duration of 12 ± 6.5 years were enrolled in this study. Mean DAS-28 ESR score for our patients was 4 ± 0.7. The pain, effusion, and reduced ROM were decreased significantly after all follow-up intervals. Knee tenderness was not affected in the first 2 weeks, but it was reduced significantly after 1, 2, and 6 months. No serious complications like infection and necrosis were reported through our study. 51.6% and 54.8% of our patients reported pain and swelling in the administration site. Furthermore, 19.4% and 16.1% of patients reported deterioration of pain and effusion in the first week of injection. Conclusion: In our study, we demonstrated that pain, tenderness, effusion, and ROM are improved after radiation synovectomy with phosphorus-32. We also showed that there was no serious adverse effect like infection and necrosis. However, more than half of our patients experienced pain and swelling of injection site at the time of administration. Key points • We demonstrated the efficacy of radiation synovectomy as a medication for monoarthritis. • The results of our study can lead to a bigger clinical trial to assess the benefits and adverse effects of radiation synovectomy in comparison to treatment with local or systemic corticosteroids. [ABSTRACT FROM AUTHOR]

In the pathogenesis of osteoarthritis, various signaling pathways may influence the bone joint through a common terminal pathway, thereby contributing to the pathological remodeling of the joint. Semaphorins (SEMAs) are cell-surface proteins actively involved in and primarily responsible for regulating chondrocyte function in the pathophysiological process of osteoarthritis (OA). The significance of the SEMA family in OA is increasingly acknowledged as pivotal. This review aims to summarize the mechanisms through which different members of the SEMA family impact various structures within joints. The findings indicate that SEMA3A and SEMA4D are particularly relevant to OA, as they participate in cartilage injury, subchondral bone remodeling, or synovitis. Additionally, other elements such as SEMA4A and SEMA5A may also contribute to the onset and progression of OA by affecting different components of the bone and joint. The mentioned mechanisms demonstrate the indispensable role of SEMA family members in OA, although the detailed mechanisms still require further exploration. [ABSTRACT FROM AUTHOR]

Rice bodies (RBs) synovitis in the shoulder joints of systemic lupus erythematosus patients is a rare clinical condition that has not been previously reported. Despite the fact that the diagnosis of RBs synovitis has primarily relied on MRI imaging, ultrasound has been used less frequently. In this report, we discuss a 43-year-old female diagnosed with systemic lupus erythematosus who presented with pain and swelling in the right shoulder. The ultrasound findings were typical, and the patient was diagnosed with RBs synovitis, as she had no history of tuberculosis or rheumatoid arthritis. Subsequently, the patient underwent ultrasound-guided percutaneous biopsy and surgical excision, which led to a good postoperative outcome. Based on this case, a literature review of RBs synovitis over the past 2 decades indicates that rice bodies synovitis is rare in clinical presentation accompanied by SLE. Moreover, ultrasound has not been extensively employed for diagnosing this condition. It is important to note the pivotal role of ultrasound in detecting RBs synovitis, and it should be the preferred method for early detection. Therefore, ultrasound physicians should be well informed about this condition to enhance diagnostic precision. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a disease with sex-dependent prevalence and severity in both human and animal models. We sought to elucidate sex differences in synovitis, mechanical sensitization, structural damage, bone remodeling, and the synovial transcriptome in the anterior cruciate ligament rupture (ACLR) mouse model of post-traumatic OA (PTOA). Male and female 12-week-old C57/BL6J mice were randomized to Sham or noninvasive ACLR with harvests at 7d or 28d post-ACLR (n = 9 per sex in each group – Sham, 7d ACLR, 28d ACLR). Knee hyperalgesia, mechanical allodynia, and intra-articular matrix metalloproteinase (MMP) activity (via intravital imaging) were measured longitudinally. Trabecular and subchondral bone (SCB) remodeling and osteophyte formation were assessed by µCT. Histological scoring of PTOA, synovitis, and anti-MMP13 immunostaining were performed. Na V 1.8-Cre;tdTomato mice were used to document localization and sprouting of nociceptors. Bulk RNA-seq of synovium in Sham, 7d, and 28d post-ACLR, and contralateral joints (n = 6 per group per sex) assessed injury-induced and sex-dependent gene expression. Male mice exhibited more severe joint damage at 7d and 28d and more severe synovitis at 28d, accompanied by 19% greater MMP activity, 8% lower knee hyperalgesia threshold, and 43% lower hindpaw withdrawal threshold in injured limbs compared to female injured limbs. Females had injury-induced catabolic responses in trabecular and SCB, whereas males exhibited 133% greater normalized osteophyte volume relative to females and sclerotic remodeling of trabecular and SCB. Na V 1.8+ nociceptor sprouting in SCB and medial synovium was induced by injury and comparable between sexes. RNA-seq of synovium demonstrated similar injury-induced transcriptomic programs between the sexes at 7d, but only female mice exhibited a transcriptomic signature indicative of synovial inflammatory resolution by 28d, whereas males had persistent pro-inflammatory, pro-fibrotic, pro-neurogenic, and pro-angiogenic gene expression. Male mice exhibited more severe overall joint damage and pain behavior after ACLR, which was associated with persistent activation of synovial inflammatory, fibrotic, and neuroangiogenic processes, implicating persistent synovitis in driving sex differences in murine PTOA. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by the degradation of joint cartilage, subchondral bone sclerosis, synovitis, and structural changes in the joint. Recent research has highlighted the role of various genes in the pathogenesis and progression of OA, with nuclear factor erythroid 2-related factor 2 (NRF2) emerging as a critical player. NRF2, a vital transcription factor, plays a key role in regulating the OA microenvironment and slowing the disease's progression. It modulates the expression of several antioxidant enzymes, such as Heme oxygenase-1 (HO-1) and NAD(P)H oxidoreductase 1 (NQO1), among others, which help reduce oxidative stress. Furthermore, NRF2 inhibits the nuclear factor kappa-B (NF-κB) signaling pathway, thereby decreasing inflammation, joint pain, and the breakdown of cartilage extracellular matrix, while also mitigating cell aging and death. This review discusses NRF2's impact on oxidative stress, inflammation, cell aging, and various cell death modes (such as apoptosis, necroptosis, and ferroptosis) in OA-affected chondrocytes. The role of NRF2 in OA macrophages, and synovial fibroblasts was also discussed. It also covers NRF2's role in preserving the cartilage extracellular matrix and alleviating joint pain. The purpose of this review is to provide a comprehensive understanding of NRF2's protective mechanisms in OA, highlighting its potential as a therapeutic target and underscoring its significance in the development of novel treatment strategies for OA. [ABSTRACT FROM AUTHOR]

The accurate diagnosis of gout frequently constitutes a challenge in clinical practice, as it bears a close resemblance to other rheumatologic conditions. An undelayed diagnosis and an early therapeutic intervention using uric acid lowering therapy (ULT) is of the utmost importance for preventing bone destruction, the main point of managing gout patients. Advanced and less invasive imaging techniques are employed to diagnose the pathology and ultrasonography (US) stands out as a non-invasive, widely accessible and easily reproducible method with high patient acceptability, enabling the evaluation of the full clinical spectrum in gout. The 2023 EULAR recommendations for imaging in diagnosis and management of crystal-induced arthropathies in clinical practice state that US is a fundamental imagistic modality. The guidelines underline its effectiveness in detecting crystal deposition, particularly for identifying tophi and the double contour sign (DCS). Its utility also arises in the early stages, consequent to synovitis detection. US measures of monosodium urate (MSU) deposits are valuable indicators, sensitive to change consequent to even short-term administration of ULT treatment, and can be feasibly used both in current daily practice and clinical trials. This paper aimed to provide an overview of the main US features observed in gout patients with reference to standardized imaging guidelines, as well as the clinical applicability both for diagnosis accuracy and treatment follow-up. Our research focused on summarizing the current knowledge on the topic, highlighting key data that emphasize gout as one of the few rheumatological conditions where US is recognized as a fundamental diagnostic and monitoring tool, as reflected in the most recent classification criteria. [ABSTRACT FROM AUTHOR]

This study presents a detailed case analysis of a 40-year-old male patient with hemophilia A and severe chronic elbow arthropathy, exploring the surgical challenges and outcomes within the context of the current literature. The patient, with a history of multiple comorbidities including Hodgkin's lymphoma and cardiomyopathy, exhibited significant joint damage and functional impairment. A comprehensive approach was employed, collecting all relevant clinical data, including radiographic and MRI findings, to inform treatment decisions. Clinical findings and treatment decisions are presented as they occurred in real time, simulating the clinical reasoning process. Subsequent references to the clinical and instrumental findings as well therapeutic interventions are discussed in light of the current literature to reinforce the decision-making framework. This report underscores the importance of multidisciplinary care in optimizing patient outcomes and contributes to the ongoing discourse on the management of advanced musculoskeletal conditions in hemophilic patients. The findings emphasize the necessity for early intervention and specialized care to mitigate complications and improve long-term prognosis. [ABSTRACT FROM AUTHOR]

Abstract Background Activated fibroblast-like synoviocytes (FLS) are drivers of synovitis and structural joint damage in rheumatoid arthritis (RA). Despite the use of disease-modifying drugs, only about 50% of RA patients reach remission in real-world settings. We used an unbiased approach to investigate the effects of standard-of-care methotrexate (MTX) and a Janus kinase inhibitor, tofacitinib (TOFA), on gene expression in RA-FLS, in order to identify untargeted disease mediators. Methods Primary RA-FLS were activated by stimulation with interleukin-1β (IL-1β) or platelet-derived growth factor + IL-1β in the presence or absence of MTX or TOFA, with or without additional inhibitors. Co-cultures of synovial cells were performed in direct and indirect systems. Cells were collected for RNA sequencing or qPCR, and supernatants were analyzed for protein concentrations. Results Six thousand three hundred fifty genes were differentially expressed, the majority being upregulated, in MTX-treated activated RA-FLS and 970 genes, the majority being downregulated, in TOFA-treated samples. Pathway analysis showed that MTX had largest effects on ‘Molecular mechanisms of cancer’ and TOFA on ‘Interferon signaling’. Targeted analysis of disease-associated genes revealed that MTX increased the expression of cell cycle-regulating genes but also of pro-inflammatory mediators like IL-1α (IL1A) and granulocyte–macrophage colony-stimulating factor, GM-CSF (CSF2). The MTX-promoted expression of CSF2 in activated RA-FLS peaked at 48 h, could be mediated via either NF-κB or AP-1 transcription factors, and was abrogated by IL-1 inhibitors (IRAK4 inhibitor and anakinra). In a co-culture setting, MTX-treatment of activated RA-FLS induced IL1B expression in macrophages. Conclusions MTX treatment induces secretion of IL-1 from activated RA-FLS which by autocrine signaling augments their release of GM-CSF. This unexpected effect of MTX might contribute to the persistence of synovitis.

Abstract Background The uncultured adipose-derived stromal vascular fraction (SVF), consisting of adipose-derived stromal cells (ADSCs), M2 macrophages (M2Φ) and others, has shown therapeutic potential against osteoarthritis (OA), however, the mechanisms underlying its therapeutic effects remain unclear. Therefore, this study investigated the effects of the SVF on OA in a human-immunodeficient rat xenotransplantation model. Methods OA model was induced in the knees of female immunodeficient rats by destabilization of the medial meniscus. Immediately after the surgery, human SVF (1 × 105), ADSCs (1 × 104), or phosphate buffered saline as a control group were transplanted into the knees. At 4 and 8 weeks postoperatively, OA progression and synovitis were analyzed by macroscopic and histological analyses, and the expression of collagen II, SOX9, MMP-13, ADAMTS-5, F4/80, CD86 (M1), CD163 (M2), and human nuclear antigen (hNA) were evaluated immunohistochemically. In vitro, flow cytometry was performed to collect CD163-positive cells as M2Φ from the SVF. Chondrocyte pellets (1 × 105) were co-cultured with SVF (1 × 105), M2Φ (1 × 104), and ADSCs (1 × 104) or alone as a control group, and the pellet size was compared. TGF-β, IL-10 and MMP-13 concentrations in the medium were evaluated using enzyme-linked immunosorbent assay. Results In comparison with the control and ADSC groups, the SVF group showed significantly slower OA progression and less synovitis with higher expression of collagen II and SOX9, lower expression of MMP-13 and ADAMTS-5, and lower F4/80 and M1/M2 ratio in the synovium. Only the SVF group showed partial expression of hNA-, CD163-, and F4/80-positive cells in the rat synovium. In vitro, the SVF, M2Φ, ADSC and control groups, in that order, showed larger pellet sizes, higher TGF-β and IL-10, and lower MMP-13 concentrations. Conclusions The M2Φ in the transplanted SVF directly affected recipient tissue, enhancing the secretion of growth factors and chondrocyte-protecting cytokines, and partially improving chondrocytes and joint homeostasis. These findings indicate that the SVF is as an effective option for regenerative therapy for OA, with mechanisms different from those of ADSCs.

Abstract Primary osteoarthritis (OA) is a prevalent degenerative joint disease that mostly affects the knee joint. It is a condition that occurs around the world. Because of the aging population and the increase in obesity prevalence, the incidence of primary OA is increasing each year. Joint replacement can completely subside the pain and minimize movement disorders caused by advanced OA, while nonsteroidal drugs and injection of sodium hyaluronate into the joint cavity can only partially relieve the pain; hence, it is critical to search for new methods to treat OA. Increasing lines of evidence show that primary OA is a chronic inflammatory disorder, with synovial inflammation as the main characteristic. Macrophages, as one of the immune cells, can be polarized to produce M1 (proinflammatory) and M2 (anti-inflammatory) types during synovial inflammation in OA. Following polarization, macrophages do not come in direct contact with chondrocytes; however, they affect chondrocyte metabolism through paracrine production of a significant quantity of inflammatory cytokines, matrix metalloproteinases, and growth factors and thus participate in inducing joint pain, cartilage injury, angiogenesis, and osteophyte formation. The main pathways that influence the polarization of macrophages are the Toll-like receptor and NF-κB pathways. The study of how macrophage polarization affects OA disease progression has gradually become one of the approaches to prevent and treat OA. Experimental studies have found that the treatment of macrophage polarization in primary OA can effectively relieve synovial inflammation and reduce cartilage damage. The present article summarizes the influence of inflammatory factors secreted by macrophages after polarization on OA disease progression, the main signaling pathways that induce macrophage differentiation, and the role of different polarized types of macrophages in OA; thus, providing a reference for preventing and treating primary OA.