Rheumatoid arthritis (RA) is a chronic autoimmune disorder which can lead to long-term joint damage and significantly reduced quality of life if not promptly diagnosed and adequately treated. Despite significant advances in treatment, about 40% of patients with RA do not respond to individual pharmacological agents and up to 20% do not respond to any of the available medications. To address this large unmet clinical need, several recent studies have focussed on an in-depth histological and molecular characterisation of the synovial tissue to drive the application of precision medicine to RA. Currently, RA patients are clinically divided into \"seropositive\" or \"seronegative\" RA, depending on the presence of routinely checked antibodies. Recent work has suggested that over the last two decades, long-term outcomes have improved significantly in seropositive RA but not in seronegative RA. Here, we present up-to-date differences in epidemiology, clinical features, and serological biomarkers in seronegative versus seropositive RA and discuss how histological and molecular synovial signatures, revealed by recent large synovial biopsy-based clinical trials, may be exploited to refine the classification of RA patients, especially in the seronegative group.

BACKGROUND: Synovial chondromatosis is a non-malignant synovial disorder characterized by the presence of cartilage formation within the synovial membrane, leading to the emergence of multiple cartilaginous nodules that may be either attached or unattached. The presence of this anatomical feature is frequently observed in articulations such as the knee, hip, elbow, and ankle.
METHODS: In this study, we present a case of synovial chondromatosis in the knee joint of a healthy male in his early 60s. Notably, the patient exhibited the simultaneous presence of 87 large loose bodies. The occurrence of a substantial quantity of unattached entities of notable dimensions within the joint is highly uncommon.
CONCLUSIONS: The patient had several synovial chondromas, a rare disease. Synovial chondromatosis is a benign disorder; however, growing synovium can cause pyogenic cartilage nodules. Most loose bodies in joints can abrade and degenerate articular cartilage, causing long-term discomfort. Thus, an early-stage procedure to remove loose bodies and carefully excise synovial tissue is necessary to treat this condition.

Osteoarthritis (OA) affects the entire joint, causing structural changes in articular cartilage, subchondral bone, ligaments, capsule, synovial membrane, and periarticular muscles that afflicts millions of people globally, leading to persistent pain and diminished quality of life. The intra-articular use of platelet-rich plasma (PRP) is gaining recognition as a secure therapeutic approach due to its potential regenerative capabilities. However, there is controversial clinical data regarding efficacy of PRP for OA treatment. In this context, gathering scientific evidence on the effects of PRP in treating OA in animal models could provide valuable insights into understanding its impact on aspects like cartilage health, synovial tissue integrity, and the inflammatory process in affected joints. Thus, the objective of this study was to assess the effects of PRP injections on inflammation and histopathological aspects of cartilage and synovium in animal models of OA through a comprehensive systematic review with meta-analysis.
A electronic search was conducted on Medline, Embase, Web of Science, The Cochrane Library, LILACS, and SciELO databases for relevant articles published until June 2022. A random-effects meta-analysis was employed to synthesize evidence on the histological characteristics of cartilage and synovium, as well as the inflammatory process. The GRADE approach was utilized to categorize the quality of evidence, and methodological quality was assessed using SYRCLE\'s RoB tool.
Twenty-one studies were included in the review, with twelve of them incorporated into the meta-analysis. PRP treatment demonstrated superior outcomes compared to the control group in terms of cartilage histology (very low quality; p = 0.0002), synovium histology (very low quality; p < 0.0001), and reductions in proinflammatory markers, including IL-1 (low quality; p = 0.002), IL-6 (very low quality; p < 0.00001), and TNF-α (very low; p < 0.00001). However, PRP treatment did not yield a significant impact on PDGF-A levels (very low quality; p = 0.81).
PRP appears capable of reducing proinflammatory markers (IL-1, IL-6, TNF-α) and mitigating cartilage and synovium damage in animals with OA. However, the levels of evidence of these findings are low to very low. Therefore, more rigorous studies with larger samples are needed to improve the quality of evidence.
CRD42022250314.

Fibroblast-like synoviocytes (FLS) are important components of the synovial membrane. They can contribute to joint damage through crosstalk with inflammatory cells and direct actions on tissue damage pathways in rheumatoid arthritis (RA). Recent evidence suggests that, compared with FLS in normal synovial tissue, FLS in RA synovial tissue exhibits significant differences in metabolism. Recent metabolomic studies have demonstrated that metabolic changes, including those in glucose, lipid, and amino acid metabolism, exist before synovitis onset. These changes may be a result of increased biosynthesis and energy requirements during the early phases of the disease. Activated T cells and some cytokines contribute to the conversion of FLS into cells with metabolic abnormalities and pro-inflammatory phenotypes. This conversion may be one of the potential mechanisms behind altered FLS metabolism. Targeting metabolism can inhibit FLS proliferation, providing relief to patients with RA. In this review, we aimed to summarize the evidence of metabolic changes in FLS in RA, analyze the mechanisms of these metabolic alterations, and assess their effect on RA phenotype. Finally, we aimed to summarize the advances and challenges faced in targeting FLS metabolism as a promising therapeutic strategy for RA in the future.

Osteoarthritis (OA) is one of the most common degenerative diseases characterised by joint pain, swelling and decreased mobility, with its main pathological features being articular synovitis, cartilage degeneration and osteophyte formation. Inflammatory cytokines and chemokines secreted by activated immunocytes can trigger various inflammatory and immune responses in articular cartilage and synovium, contributing to the genesis and development of OA. A series of monocyte/macrophage chemokines, including monocyte chemotaxis protein (MCP)-1/CCL2, MCP2/CCL8, macrophage inflammatory protein (MIP)-1α/CCL3, MIP-1β/CCL4, MIP-3α/CCL20, regulated upon activation, normal T-cell expressed and secreted /CCL5, CCL17 and macrophage-derived chemokine/CCL22, was proven to transmit cell signals by binding to G protein-coupled receptors on recipient cell surface, mediating and promoting inflammation in OA joints. However, the underlying mechanism of these chemokines in the pathogenesis of OA remains still elusive. Here, published literature was reviewed, and the function and mechanisms of monocyte/macrophage chemokines in OA pathogenesis were summarised. The symptoms and disease progression of OA were found to be effectively alleviated when the expression of these chemokines is inhibited. Elucidating these mechanisms could contribute to further understand how OA develops and provide potential targets for the early diagnosis of arthritis and drug treatment to delay or even halt OA progression.

Recent evidence highlights the role of low-grade synovial inflammation in the progression of osteoarthritis (OA). Inflamed synovium of OA joints detected by imaging modalities are associated with subsequent progression of OA. In this sense, detecting and quantifying synovitis of OA by imaging modalities may be valuable in predicting OA progressors as well as in improving our understanding of OA progression. Of the several imaging modalities, molecular imaging such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) has an advantage of visualizing the cellular or subcellular events of the tissues. Depending on the radiotracers used, molecular imaging method can potentially detect and visualize various aspects of synovial inflammation. This narrative review summarizes the recent progresses of imaging modalities in assessing inflammation and OA synovitis and focuses on novel radiotracers. Recent studies about imaging modalities including ultrasonography (US), magnetic resonance imaging (MRI), and molecular imaging that were used to detect and quantify inflammation and OA synovitis are summarized. Novel radiotracers specifically targeting the components of inflammation have been developed. These tracers may show promise in detecting inflamed synovium of OA and help in expanding our understanding of OA progression.

Rheumatoid arthritis (RA) is characterized by synovial edema, inflammation, bone and cartilage loss, and joint degradation. Patients experience swelling, stiffness, pain, limited joint movement, and decreased mobility as the condition worsens. RA treatment regimens often come with various side effects, including an increased risk of developing cancer and organ failure, potentially leading to mortality. However, researchers have proposed mechanistic hypotheses to explain the underlying causes of synovitis and joint damage in RA patients. This review article focuses on the role of synoviocytes and synoviocytes resembling fibroblasts in the RA synovium. Additionally, it explores the involvement of epigenetic regulatory systems, such as microRNA pathways, silent information regulator 1 (SIRT1), Peroxisome proliferatoractivated receptor-gamma coactivator (PGC1-α), and protein phosphatase 1A (PPM1A)/high mobility group box 1 (HMGB1) regulators. These mechanisms are believed to modulate the function of receptors, cytokines, and growth factors associated with RA. The review article includes data from preclinical and clinical trials that provide insights into potential treatment options for RA.

Temporomandibular joints (TMJ) are one of the most complex joints. Each one is located on one side of the face, and are composed of mandibular fossa, joint tubercle, and condylar process of mandible, separated by an articular disk. To these structures are attached ligaments and muscles, which will provide stability and movement. When TMJs work properly, jaw movements can be performed without pain or discomfort. It is important to mention that the complex formed by both TMJs will confront the maxillary with the mandibular bone and therefore will be related to the occlusion, linking these structures during growth and development.

Temporomandibular joint disorders (TMDs) are conditions that affect the muscles of mastication and joints that connect the mandible to the base of the skull. Although TMJ disorders are associated with symptoms, the causes are not well proven. Chemokines play an important role in the pathogenesis of TMJ disease by promoting chemotaxis inflammatory cells to destroy the joint synovium, cartilage, subchondral bone, and other structures. Therefore, enhancing our understanding of chemokines is critical for developing appropriate treatment of TMJ. In this review, we discuss chemokines including MCP-1, MIP-1α, MIP-3a, RANTES, IL-8, SDF-1, and fractalkine that are known to be involved in TMJ diseases. In addition, we present novel findings that CCL2 is involved in β-catenin-mediated TMJ osteoarthritis (OA) and potential molecular targets for the development of effective therapies. The effects of common inflammatory factors, IL-1β and TNF-α, on chemotaxis are also described. In conclusion, this review aims to provide a theoretical basis for future chemokine-targeted therapies for TMJ OA.

OBJECTIVE: Aim of this systematic review was to determine if bone marrow-derived cell-based injectable therapies induce disease-modifying effects in joints affected by osteoarthritis (OA) in animal models.
METHODS: A systematic review was performed on three electronic databases (PubMed, Web of Science, Embase) according to PRISMA guidelines. A synthesis of the results was performed investigating disease-modifying effects in preclinical animal studies comparing injectable bone marrow-derived products with OA controls or other products, different formulations or injection intervals, and the combination with other products. The risk of bias was assessed according to the SYRCLE\'s tool.
RESULTS: Fifty-three studies were included (1819 animals) with an increasing publication trend over time. Expanded cells were used in 48 studies, point-of-care products in 3 studies, and both approaches were investigated in 2 studies. Among the 47 studies presenting results on the disease-modifying effects, 40 studies (85%) reported better results with bone marrow-derived products compared to OA controls, with positive findings evident in 14 out of 20 studies (70%) in macroscopic assessment, in 30 out of 41 studies (73%) in histological assessment, and in 10 out of 13 studies (77%) in immunohistochemical evaluations. Clinical evaluations showed positive results in 7 studies out of 9 (78%), positive imaging results in 11 studies out of 17 (65%), and positive biomarker results in 5 studies out of 10 (50%). While 36 out of 46 studies (78%) reported positive results at the cartilage level, only 3 out of 10 studies (30%) could detect positive changes at the synovial level. The risk of bias was low in 42% of items, unclear in 50%, and high in 8%.
CONCLUSIONS: This systematic review of preclinical studies demonstrated that intra-articular injections of bone marrow-derived products can induce disease-modifying effects in the treatment of OA, slowing down the progression of cartilage damage with benefits at macroscopic, histological, and immunohistochemical levels. Positive results have been also observed in terms of clinical and imaging findings, as well as in the modulation of inflammatory and cartilage biomarkers, while poor effects have been described on the synovial membrane. These findings are important to understand the potential of bone marrow-derived products and to guide further research to optimise their use in the clinical practice.
METHODS: II.