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Clinical Rheumatology Jul 2021Synovial biopsy techniques have developed and widely expanded over the past few years, in particular due to the development of ultrasound-guided procedures. This article... (Review)
Review
Synovial biopsy techniques have developed and widely expanded over the past few years, in particular due to the development of ultrasound-guided procedures. This article reviews the different techniques, clinical applications, and the latest advances in translational research as well as current challenges and perspectives. The first part focuses on different techniques available for biopsy, along with their feasibility, success rate, tolerance, and training requirements. In the second part, clinical applications are described. Data on diagnostic performances are reported, especially regarding septic arthritis. Translational research applications are described and explained in the final part, from the early histological studies and the first description of pathotype to more recent technologies involving -omics. Latest developments involving single-cell RNA sequence analysis have allowed the discovery of new cell subpopulations with remarkable roles in RA pathophysiology. These studies pave the ground for the discovery of new therapeutic targets and the implementation of personalized therapy in RA. Key Point •This review provides an overview of synovial biopsy techinques and applications especially in clinical and translational research.
Topics: Arthritis, Infectious; Biopsy; Humans; Synovial Membrane; Synovitis; Ultrasonography
PubMed: 33274415
DOI: 10.1007/s10067-020-05512-7 -
Frontiers in Immunology 2023Fibroblast-activated protein-α (FAP) is a type II integrated serine protease expressed by activated fibroblasts during fibrosis or inflammation. Fibroblast-like... (Review)
Review
Fibroblast-activated protein-α (FAP) is a type II integrated serine protease expressed by activated fibroblasts during fibrosis or inflammation. Fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) synovial sites abundantly and stably overexpress FAP and play important roles in regulating the cellular immune, inflammatory, invasion, migration, proliferation, and angiogenesis responses in the synovial region. Overexpression of FAP is regulated by the initial inflammatory microenvironment of the disease and epigenetic signaling, which promotes RA development by regulating FLSs or affecting the signaling cross-linking FLSs with other cells at the local synovium and inflammatory stimulation. At present, several treatment options targeting FAP are in the process of development. This review discusses the basic features of FAP expressed on the surface of FLSs and its role in RA pathophysiology and advances in targeted therapies.
Topics: Humans; Synoviocytes; Cell Proliferation; Arthritis, Rheumatoid; Synovial Membrane; Fibroblasts
PubMed: 37006278
DOI: 10.3389/fimmu.2023.1135384 -
Journal of Orthopaedic Research :... Aug 2017Joint pathology and degeneration is a significant cause of pain. The synovial membrane plays an important role in maintenance of the joint, contributes to the pathology... (Review)
Review
Joint pathology and degeneration is a significant cause of pain. The synovial membrane plays an important role in maintenance of the joint, contributes to the pathology of many arthropathies and may be adversely affected in joint disease. Improving knowledge of the receptors present within the synovium will aid in a better understanding of joint pathology and the development of new treatments for diseases such as osteoarthritis and rheumatoid arthritis. Knowledge of the location and function of synovial membrane receptors (both in healthy and diseased synovium) may provide important targets in the treatment of various arthropathies. Classic pain receptors such as opioid receptors in the synovium are a mainstay in local and systemic management of chronic pain in many species. In addition to these, many other receptors such as bradykinin, neurokinin, transient receptor potential vanilloid, and inflammatory receptors, such as prostanoid and interleukin receptors have been discovered within the synovial membrane. These receptors are important in pain, inflammation, and in maintenance of normal joint function and may serve as targets for pharmacologic intervention in pathologic states. The goal of this review is to outline synovial membrane receptor localization and local therapeutic modulation of these receptors, in order to stimulate further research into pharmacological management of arthropathies at the local level. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1589-1605, 2017.
Topics: Animals; Humans; Joint Diseases; Molecular Targeted Therapy; Receptors, Cell Surface; Receptors, Cytoplasmic and Nuclear; Synovial Membrane
PubMed: 28374922
DOI: 10.1002/jor.23568 -
Stem Cell Research & Therapy Sep 2020Mesenchymal stem cells (MSCs) can be isolated from not only bone marrow, but also various adult mesenchymal tissues such as periosteum, skeletal muscle, and adipose... (Review)
Review
Mesenchymal stem cells (MSCs) can be isolated from not only bone marrow, but also various adult mesenchymal tissues such as periosteum, skeletal muscle, and adipose tissue. MSCs from different tissue sources have different molecular phenotypes and differentiation potential. Synovial membrane (SM) is an important and highly specific component of synovial joints. Previous studies have suggested that the synovium is a structure with a few cell layers thick and consists mainly of fibroblast-like synoviocytes (FLS), which forms a layer that lining the synovial membrane on the joint cavity and synovial fluid through cell-cell contact. In recent years, studies have found that there are also mesenchymal stem cells in the synovium, and as an important part of the mesenchymal stem cell family, it has strong capabilities of cartilage forming and tissue repairing. This article reviews the sources, surface markers, subtypes, influencing factors, and applications in inflammatory joints of synovial membrane mesenchymal stem cells (SM-MSCs) in recent years, aiming to clarify the research status and existing problems of SM-MSCs.
Topics: Adult; Cell Differentiation; Chondrogenesis; Humans; Joint Diseases; Mesenchymal Stem Cells; Synovial Fluid; Synovial Membrane
PubMed: 32894205
DOI: 10.1186/s13287-020-01885-3 -
International Journal of Molecular... Nov 2020Rheumatoid arthritis (RA) is a systemic chronic inflammatory autoimmune joint disease, characterized by progressive articular damage and joint dysfunction. One of the... (Review)
Review
Rheumatoid arthritis (RA) is a systemic chronic inflammatory autoimmune joint disease, characterized by progressive articular damage and joint dysfunction. One of the symptoms of this disease is persistent inflammatory infiltration of the synovial membrane, the principle site of inflammation in RA. In the affected conditions, the cells of the synovial membrane, fibroblast-like synoviocytes and macrophage-like synovial cells, produce enzymes degrading cartilage and underlining bone tissue, as well as cytokines increasing the infiltration of immune cells. In patients with RA, higher levels of adiponectin are measured in the serum and synovial fluid. Adiponectin, a secretory product that is mainly white adipose tissue, is a multifunctional protein with dual anti-inflammatory and pro-inflammatory properties. Several studies underline the fact that adiponectin can play an important pro-inflammatory role in the pathophysiology of RA via stimulating the secretion of inflammatory mediators. This narrative review is devoted to the presentation of recent knowledge on the role played by one of the adipokines produced by adipose tissue-adiponectin-in the pathogenesis of rheumatoid arthritis.
Topics: Adipokines; Adiponectin; Adipose Tissue; Arthritis, Rheumatoid; Humans; Inflammation; Inflammation Mediators; Synovial Membrane; Synoviocytes
PubMed: 33158216
DOI: 10.3390/ijms21218265 -
Cells Oct 2019The synovium exercises its main function in joint homeostasis through the secretion of factors (such as lubricin and hyaluronic acid) that are critical for the joint... (Review)
Review
The synovium exercises its main function in joint homeostasis through the secretion of factors (such as lubricin and hyaluronic acid) that are critical for the joint lubrication and function. The main synovium cell components are fibroblast-like synoviocytes, mesenchymal stromal/stem cells and macrophage-like synovial cells. In the synovium, cells of mesenchymal origin modulate local inflammation and fibrosis, and interact with different fibroblast subtypes and with resident macrophages. In pathologic conditions, such as rheumatoid arthritis, fibroblast-like synoviocytes proliferate abnormally, recruit mesenchymal stem cells from subchondral bone marrow, and influence immune cell activity through epigenetic and metabolic adaptations. The resulting synovial hyperplasia leads to secondary cartilage destruction, joint swelling, and pain. In the present review, we summarize recent findings on the molecular signature and the roles of stromal cells during synovial pannus formation and rheumatoid arthritis progression.
Topics: Arthritis, Rheumatoid; Fibroblasts; Humans; Inflammation; Mesenchymal Stem Cells; Stromal Cells; Synovial Membrane; Synoviocytes; Synovitis
PubMed: 31618926
DOI: 10.3390/cells8101257 -
BMC Musculoskeletal Disorders Mar 2023Immune and non-immune cells contribute to the pathology of chronic arthritis, and they can contribute to tissue remodeling and repair as well as disease pathogenesis....
BACKGROUND
Immune and non-immune cells contribute to the pathology of chronic arthritis, and they can contribute to tissue remodeling and repair as well as disease pathogenesis. The present research aimed to analyze inflammation and bone destruction/regeneration biomarkers in patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), osteoarthritis (OA), and ankylosing spondylitis (AS).
METHODS
Samples were obtained from the inflamed knee of patients with knee arthritis who had been referred for undergoing arthroscopies. The synovial membrane was processed for pathological description, IHC analysis, and quantification of mRNA expression ratio by qRT-PCR. Serum levels of TGF-β1, IL-23, IL-6, IL-17 A, IL-22, Dkk1, Sclerostin, BMP2, BMP4, Wnt1, and Wnt5a were measured by ELISA. All these data were analyzed and compared with the demographic, clinical, blood tests, and radiological characteristics of the patients.
RESULTS
The synovial membrane samples were obtained from 42 patients for IHC, extraction, and purification of RNA for synovial mRNA expression analysis, and serum for measuring protein levels from 38 patients. IHC reactivity for TGF-β1 in the synovial tissue was higher in patients with psoriatic arthritis (p 0.036) and was positively correlated with IL-17 A (r = 0.389, p = 0.012), and Dkk1 (r = 0.388, p = 0.012). Gene expression of the IL-17 A was higher in PsA patients (p = 0.018) and was positively correlated with Dkk1 (r = 0.424, p = 0.022) and negatively correlated with BMP2 (r = -0.396, p = 0.033) and BMP4 (r = -0.472, p = 0.010). It was observed that IHC reactivity for TGF-β1 was higher in patients with erosive PsA (p = 0.024).
CONCLUSIONS
The IHC reactivity of TGF-β1 in synovial tissue was higher in patients with erosive psoriatic arthritis, and TGF-β1 was in relation to higher levels of gene expression of IL-17 A and Dkk1.
Topics: Humans; Arthritis, Psoriatic; Transforming Growth Factor beta1; Interleukin-17; Synovial Fluid; Immunohistochemistry; Synovial Membrane; RNA, Messenger
PubMed: 36997896
DOI: 10.1186/s12891-023-06339-4 -
Annals of the Rheumatic Diseases Dec 2023Transcriptomic profiling of synovial tissue from patients with early, untreated rheumatoid arthritis (RA) was used to explore the ability of unbiased, data-driven...
OBJECTIVES
Transcriptomic profiling of synovial tissue from patients with early, untreated rheumatoid arthritis (RA) was used to explore the ability of unbiased, data-driven approaches to define clinically relevant subgroups.
METHODS
RNASeq was performed on 74 samples, with disease activity data collected at inclusion. Principal components analysis (PCA) and unsupervised clustering were used to define patient clusters based on expression of the most variable genes, followed by pathway analysis and inference of relative abundance of immune cell subsets. Histological assessment and multiplex immunofluorescence (for CD45, CD68, CD206) were performed on paraffin sections.
RESULTS
PCA on expression of the (n=894) most variable genes across this series did not divide samples into distinct groups, instead yielding a continuum correlated with baseline disease activity. Two patient clusters (PtC1, n=52; PtC2, n=22) were defined based on expression of these genes. PtC1, with significantly higher disease activity and probability of response to methotrexate therapy, showed upregulation of immune system genes; PtC2 showed upregulation of lipid metabolism genes, described to characterise tissue resident or M2-like macrophages. In keeping with these data, M2-like:M1-like macrophage ratios were inversely correlated with disease activity scores and were associated with lower synovial immune infiltration and the presence of thinner, M2-like macrophage-rich synovial lining layers.
CONCLUSION
In this large series of early, untreated RA, we show that the synovial transcriptome closely mirrors clinical disease activity and correlates with synovial inflammation. Intriguingly, lower inflammation and disease activity are associated with higher ratios of M2:M1 macrophages, particularly striking in the synovial lining layer. This may point to a protective role for tissue resident macrophages in RA.
Topics: Humans; Transcriptome; Synovitis; Arthritis, Rheumatoid; Synovial Membrane; Inflammation
PubMed: 37507201
DOI: 10.1136/ard-2023-224068 -
Journal of Biomedical Science Aug 2016Alterations in tissue oxygen pressure contribute to a number of diseases, including rheumatoid arthritis (RA). Low partial pressure of oxygen, a condition known as... (Review)
Review
Alterations in tissue oxygen pressure contribute to a number of diseases, including rheumatoid arthritis (RA). Low partial pressure of oxygen, a condition known as hypoxia, is a relevant feature in RA since it is involved in angiogenesis, inflammation, apoptosis, cartilage degradation, energy metabolism, and oxidative damage. Therefore, alterations in hypoxia-related signaling pathways are considered potential mechanisms of disease pathogenesis. The objective of this review is to highlight and update our current knowledge of the role of hypoxia in the pathogenesis of RA. We describe the experimental evidence that RA synovial tissue exists in a hypoxic state, as well as the origin and involvement of synovial hypoxia in different aspects of the pathogenic process.
Topics: Anaerobiosis; Arthritis, Rheumatoid; Humans; Neovascularization, Pathologic; Synovial Membrane
PubMed: 27549205
DOI: 10.1186/s12929-016-0281-0 -
Seminars in Immunopathology Jun 2017The profound alterations in the structure, cellular composition, and function of synovial tissue in rheumatoid arthritis (RA) are the basis for the persistent... (Review)
Review
The profound alterations in the structure, cellular composition, and function of synovial tissue in rheumatoid arthritis (RA) are the basis for the persistent inflammation and cumulative joint destruction that are hallmarks of this disease. In RA, the synovium develops characteristics of a tertiary lymphoid organ, with extensive infiltration of lymphocytes and myeloid cells. Concurrently, the fibroblast-like synoviocytes undergo massive hyperplasia and acquire a tissue-invasive phenotype. In this review, we summarize key components of these processes, focusing on recently-described roles of selected molecular markers of these cellular components of RA synovitis.
Topics: Animals; Antirheumatic Agents; Arthritis, Rheumatoid; Biomarkers; Cell Communication; Gene Expression Regulation; Humans; Joint Capsule; Molecular Targeted Therapy; Signal Transduction; Synovial Membrane
PubMed: 28497350
DOI: 10.1007/s00281-017-0631-3