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Arthritis Research & Therapy Feb 2017Modern concepts of osteoarthritis (OA) have been forever changed by modern imaging phenotypes demonstrating complex and multi-tissue pathologies involving cartilage,... (Review)
Review
Modern concepts of osteoarthritis (OA) have been forever changed by modern imaging phenotypes demonstrating complex and multi-tissue pathologies involving cartilage, subchondral bone and (increasingly recognized) inflammation of the synovium. The synovium may show significant changes, even before visible cartilage degeneration has occurred, with infiltration of mononuclear cells, thickening of the synovial lining layer and production of inflammatory cytokines. The combination of sensitive imaging modalities and tissue examination has confirmed a high prevalence of synovial inflammation in all stages of OA, with a number of studies demonstrating that synovitis is related to pain, poor function and may even be an independent driver of radiographic OA onset and structural progression. Treating key aspects of synovial inflammation therefore holds great promise for analgesia and also for structure modification. This article will review current knowledge on the prevalence of synovitis in OA and its role in symptoms and structural progression, and explore lessons learnt from targeting synovitis therapeutically.
Topics: Cartilage, Articular; Cytokines; Disease Progression; Humans; Inflammation Mediators; Knee Joint; Models, Biological; Osteoarthritis; Synovial Membrane; Synovitis
PubMed: 28148295
DOI: 10.1186/s13075-017-1229-9 -
Arthritis and Rheumatism Sep 2010The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized...
OBJECTIVE
The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA.
METHODS
A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease--this being the appropriate current paradigm underlying the disease construct "rheumatoid arthritis."
RESULTS
In the new criteria set, classification as "definite RA" is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0-5), serologic abnormality (score range 0-3), elevated acute-phase response (score range 0-1), and symptom duration (2 levels; range 0-1).
CONCLUSION
This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimize the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct "rheumatoid arthritis."
Topics: Acute-Phase Reaction; Algorithms; Arthritis, Rheumatoid; Early Diagnosis; Europe; Humans; International Cooperation; North America; Severity of Illness Index; Societies, Medical; Synovitis; Terminology as Topic; Time Factors
PubMed: 20872595
DOI: 10.1002/art.27584 -
Bone Aug 2012Research into the pathophysiology of osteoarthritis (OA) has focused on cartilage and peri-articular bone, but there is increasing recognition that OA affects all of the... (Review)
Review
Research into the pathophysiology of osteoarthritis (OA) has focused on cartilage and peri-articular bone, but there is increasing recognition that OA affects all of the joint tissues, including the synovium (SM). Under normal physiological conditions the synovial lining consists of a thin layer of cells with phenotypic features of macrophages and fibroblasts. These cells and the underlying vascularized connective tissue stroma form a complex structure that is an important source of synovial fluid (SF) components that are essential for normal cartilage and joint function. The histological changes observed in the SM in OA generally include features indicative of an inflammatory "synovitis"; specifically they encompass a range of abnormalities, such as synovial lining hyperplasia, infiltration of macrophages and lymphocytes, neoangiogenesis and fibrosis. The pattern of synovial reaction varies with disease duration and associated metabolic and structural changes in other joint tissues. Imaging modalities including magnetic resonance (MRI) and ultrasound (US) have proved useful in detecting and quantifying synovial abnormalities, but individual studies have varied in their methods of evaluation. Despite these differences, most studies have concluded that the presence of synovitis in OA is associated with more severe pain and joint dysfunction. In addition, synovitis may be predictive of faster rates of cartilage loss in certain patient populations. Recent studies have provided insights into the pathogenic mechanisms underlying the development of synovitis in OA. Available evidence suggests that the inflammatory process involves engagement of Toll-like receptors and activation of the complement cascade by degradation products of extracellular matrices of cartilage and other joint tissues. The ensuing synovial reaction can lead to synthesis and release of a wide variety of cytokines and chemokines. Some of these inflammatory mediators are detected in joint tissues and SF in OA and have catabolic effects on chondrocytes. These inflammatory mediators represent potential targets for therapeutic interventions designed to reduce both symptoms and structural joint damage in OA. This article is part of a Special Issue entitled "Osteoarthritis".
Topics: Animals; Disease Progression; Humans; Inflammation Mediators; Osteoarthritis; Signal Transduction; Synovial Membrane; Synovitis
PubMed: 22387238
DOI: 10.1016/j.bone.2012.02.012 -
Clinics in Geriatric Medicine May 2022Chronic pain is a substantial personal and societal burden worldwide. Osteoarthritis (OA) is one of the leading causes of chronic pain and is increasing in prevalence in... (Review)
Review
Chronic pain is a substantial personal and societal burden worldwide. Osteoarthritis (OA) is one of the leading causes of chronic pain and is increasing in prevalence in accordance with a global aging population. In addition to affecting patients' physical lives, chronic pain also adversely affects patients' mental wellbeing. However, there remain no pharmacologic interventions to slow down the progression of OA and pain-alleviating therapies are largely unsuccessful. The presence of low-level inflammation in OA has been recognized for many years as a major pathogenic driver of joint damage. Inflammatory mechanisms can occur locally in joint tissues, such as the synovium, within the sensory nervous system, as well as systemically, caused by modifiable and unmodifiable factors. Understanding how inflammation may contribute to, and modify pain in OA will be instrumental in identifying new druggable targets for analgesic therapies. In this narrative review, we discuss recent insights into inflammatory mechanisms in OA pain. We discuss how local inflammation in the joint can contribute to mechanical sensitization and to the structural neuroplasticity of joint nociceptors, through pro-inflammatory factors such as nerve growth factor, cytokines, and chemokines. We consider the role of synovitis, and the amplifying mechanisms of neuroimmune interactions. We then explore emerging evidence around the role of neuroinflammation in the dorsal root ganglia and dorsal horn. Finally, we discuss how systemic inflammation associated with obesity may modify OA pain and suggest future research directions.
Topics: Aged; Chronic Pain; Humans; Inflammation; Osteoarthritis; Synovial Membrane; Synovitis
PubMed: 35410677
DOI: 10.1016/j.cger.2021.11.013 -
ELife May 2023Obesity has always been considered a significant risk factor in osteoarthritis (OA) progression, but the underlying mechanism of obesity-related inflammation in OA...
Obesity has always been considered a significant risk factor in osteoarthritis (OA) progression, but the underlying mechanism of obesity-related inflammation in OA synovitis remains unclear. The present study found that synovial macrophages infiltrated and polarized in the obesity microenvironment and identified the essential role of M1 macrophages in impaired macrophage efferocytosis using pathology analysis of obesity-associated OA. The present study revealed that obese OA patients and mice showed a more pronounced synovitis and enhanced macrophage infiltration in synovial tissue, accompanied by dominant M1 macrophage polarization. Obese OA mice had a more severe cartilage destruction and increased levels of synovial apoptotic cells (ACs) than OA mice in the control group. Enhanced M1-polarized macrophages in obese synovium decreased growth arrest-specific 6 (GAS6) secretion, resulting in impaired macrophage efferocytosis in synovial ACs. Intracellular contents released by accumulated ACs further triggered an immune response and lead to a release of inflammatory factors, such as TNF-α, IL-1β, and IL-6, which induce chondrocyte homeostasis dysfunction in obese OA patients. Intra-articular injection of GAS6 restored the phagocytic capacity of macrophages, reduced the accumulation of local ACs, and decreased the levels of TUNEL and Caspase-3 positive cells, preserving cartilage thickness and preventing the progression of obesity-associated OA. Therefore, targeting macrophage-associated efferocytosis or intra-articular injection of GAS6 is a potential therapeutic strategy for obesity-associated OA.
Topics: Animals; Mice; Macrophages; Obesity; Osteoarthritis; Synovial Membrane; Synovitis; Humans
PubMed: 37144868
DOI: 10.7554/eLife.83069 -
Osteoarthritis and Cartilage Jan 2013Osteoarthritis (OA) has long been considered a "wear and tear" disease leading to loss of cartilage. OA used to be considered the sole consequence of any process leading... (Review)
Review
Osteoarthritis (OA) has long been considered a "wear and tear" disease leading to loss of cartilage. OA used to be considered the sole consequence of any process leading to increased pressure on one particular joint or fragility of cartilage matrix. Progress in molecular biology in the 1990s has profoundly modified this paradigm. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an "inflammatory" theory. However, it took a decade before synovitis was accepted as a critical feature of OA, and some studies are now opening the way to consider the condition a driver of the OA process. Recent experimental data have shown that subchondral bone may have a substantial role in the OA process, as a mechanical damper, as well as a source of inflammatory mediators implicated in the OA pain process and in the degradation of the deep layer of cartilage. Thus, initially considered cartilage driven, OA is a much more complex disease with inflammatory mediators released by cartilage, bone and synovium. Low-grade inflammation induced by the metabolic syndrome, innate immunity and inflammaging are some of the more recent arguments in favor of the inflammatory theory of OA and highlighted in this review.
Topics: Animals; Bone and Bones; Cartilage, Articular; Chondrocytes; Humans; Immunity, Innate; Inflammation Mediators; Mice; Osteoarthritis; Synovitis
PubMed: 23194896
DOI: 10.1016/j.joca.2012.11.012 -
Haemophilia : the Official Journal of... Feb 2021Joint bleeds cause major morbidity in haemophilia patients. The synovial tissue is responsible for removal of blood remnants from the joint cavity. But blood components,... (Review)
Review
Joint bleeds cause major morbidity in haemophilia patients. The synovial tissue is responsible for removal of blood remnants from the joint cavity. But blood components, especially iron, lead to a series of changes in the synovial tissue: inflammation, proliferation and neovascularization. These changes make the synovium vulnerable to subsequent bleeding and as such a vicious cycle of bleeding-synovitis-bleeding may develop leading to chronic synovitis. The initial step in the treatment is adequate clotting factor supplementation and immediate physiotherapeutic involvement. If these measures fail, synovectomy may be indicated. Non-surgical options are chemical and radioactive synovectomy. This is a relatively non-invasive procedure to do synovectomy, leading to a reduction in pain and joint bleeds. Radioactive synovectomy seems more effective than chemical synovectomy in larger joints. Surgical options are open and arthroscopic synovectomy. Open synovectomy has been found to decrease the incidence of breakthrough bleeds but at the cost of loss of joint motion. Use of arthroscopic synovectomy has been advocated to reduce bleeding episodes with less morbidity to extra-articular tissue and preservation of joint motion. Use of a continuous passive motion (CPM) machine and early mobilization can decrease the postoperative stiffness and promote early recovery. This review addresses the current understanding of synovitis and its treatment options with specific emphasis on chemical and radioactive synovectomy and surgical options.
Topics: Arthroscopy; Hemophilia A; Humans; Knee Joint; Recurrence; Synovectomy; Synovitis
PubMed: 32490595
DOI: 10.1111/hae.14025 -
Type 2 diabetes and the risk of synovitis-tenosynovitis: a two-sample Mendelian randomization study.Frontiers in Public Health 2023It has been shown that people with type 2 diabetes have a higher risk of synovitis and tenosynovitis, but previous studies were mainly observational, which may be biased...
INTRODUCTION
It has been shown that people with type 2 diabetes have a higher risk of synovitis and tenosynovitis, but previous studies were mainly observational, which may be biased and does not allow for a cause-and-effect relationship. Therefore, we conducted a two-sample Mendelian randomization (MR) study to investigate the causal relationship.
METHOD
We obtained data on "type 2 diabetes" and "synovitis, tenosynovitis" from published large-scale genome-wide association studies (GWAS). The data were obtained from the FinnGen consortium and UK Biobank, both from European population samples. We used three methods to perform a two-sample MR analysis and also performed sensitivity analysis.
RESULTS
The results of all three MR methods we used for the analysis illustrated that T2DM increases the risk factor for the development of synovitis and tenosynovitis. Specifically, for the IVW method as the primary analysis outcome, OR = 1.0015 (95% CI, 1.0005 to 1.0026), = 0.0047; for the MR Egger method as the supplementary analysis outcome, OR = 1.0032 (95% CI, 1.0007 to 1.0056), = 0.0161; for the weighted median method, OR = 1.0022 (95% CI, 1.0008 to 1.0037), = 0.0018. In addition, the results of our sensitivity analysis suggest the absence of heterogeneity and pleiotropy in our MR analysis.
CONCLUSION
In conclusion, the results of our MR analysis suggest that T2DM is an independent risk factor for increased synovitis and tenosynovitis.
Topics: Humans; Tenosynovitis; Genome-Wide Association Study; Mendelian Randomization Analysis; Synovitis; Diabetes Mellitus, Type 2
PubMed: 37213626
DOI: 10.3389/fpubh.2023.1142416 -
Current Rheumatology Reports Oct 2020Synovial inflammation is characteristic of inflammatory chronic arthropathies and can cause progressive articular damage, chronic pain, and functional loss. Scientific... (Review)
Review
PURPOSE OF REVIEW
Synovial inflammation is characteristic of inflammatory chronic arthropathies and can cause progressive articular damage, chronic pain, and functional loss. Scientific research has increasingly focused on investigating anti-inflammatory micronutrients present in fruits, vegetables, spices, seeds, tea, and wine. This review aims to examine the anti-inflammatory effect of polyphenols (phytonutrients present in plants) and other micronutrients described in randomized clinical trials conducted in patients with chronic inflammatory arthropathies.
RECENT FINDINGS
There is an increasing evidence that differences in micronutrient intake might play an essential role in pathogenesis, therapeutic response, and remission of synovitis. Randomized clinical trials with specific micronutrient- or nutrient-enriched food intake show improvement of symptoms and modulation of both pro- and anti-inflammatory mediators. We found convincing evidence of the anti-inflammatory effect of several micronutrients in arthritis symptoms and inflammation. Although in clinical practice nutritional recommendations to patients with chronic joint inflammation are not consistently prescribed, the addition of these nutrients to day-to-day eating habits could potentially change the natural history of inflammatory arthritis. Future research is needed for a consensus on the specific nutritional recommendations for patients with chronic synovial inflammation.
Topics: Arthritis; Humans; Inflammation; Joints; Micronutrients; Synovitis
PubMed: 33104882
DOI: 10.1007/s11926-020-00962-z -
Current Allergy and Asthma Reports Feb 2021The purpose of this review is to provide a framework to distinguish Blau syndrome/Early Onset Sarcoidosis and Sarcoidosis clinically. We also discuss relevant... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to provide a framework to distinguish Blau syndrome/Early Onset Sarcoidosis and Sarcoidosis clinically. We also discuss relevant differences in genetics, pathogenesis, and management of these diseases.
RECENT FINDINGS
Blau syndrome and Sarcoidosis share the characteristic histologic finding of noncaseating granulomas as well as some similar clinical characteristics; nevertheless, they are distinct entities with important differences between them. Blau syndrome and Early Onset Sarcoidosis are due to one of numerous possible gain-of-function mutations in NOD2, commonly presenting before age 5 with a triad of skin rash, arthritis, and uveitis. However, as more cases are reported, expanded clinical manifestations have been described. In systemic Sarcoidosis, there are numerous susceptibility genes that have been identified, and disease is thought to result from an environmental exposure in a genetically susceptible host. It most often presents with constitutional symptoms and pulmonary involvement and typically affects adolescents and adults. This paper reviews the similarities and differences between Blau syndrome and Sarcoidosis. We also discuss the importance of distinguishing between them, particularly with regard to prognosis and outcomes.
Topics: Arthritis; Diagnosis, Differential; Granuloma; Humans; Mutation; Nod2 Signaling Adaptor Protein; Prognosis; Sarcoidosis; Synovitis; Uveitis
PubMed: 33560445
DOI: 10.1007/s11882-021-00991-3