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Frontiers in Immunology 2019Synovial tissue is a membranous non-immune organ lining joint cavities where it supports local immune responses, and functions directly and indirectly in joint... (Review)
Review
Synovial tissue is a membranous non-immune organ lining joint cavities where it supports local immune responses, and functions directly and indirectly in joint destruction due to chronic inflammatory diseases such as rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS), the dominant non-immune cells of synovial tissues, mainly contribute to joint destruction via multiple mechanisms. In RA, FLS respond to endogenous ligands of pattern recognition receptors (PRRs) and inflammatory cytokines as non-immune cells. In addition, FLS aid in the activation of immune responses by interacting with immune cells and by supporting ectopic lymphoid-like structure (ELS) formation in synovial tissues. Moreover, FLS directly cause the pathogenicity of RA i.e., joint deformities. Here, we describe new findings and review the mechanisms underlying the regulation of immune reactions by non-immune FLS and their roles in inflammatory diseases such as RA.
Topics: Animals; Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Cell Communication; Chronic Disease; Disease Susceptibility; Fibroblasts; Humans; Immunomodulation; Macrophages; Synovial Membrane; Synoviocytes; T-Lymphocytes
PubMed: 31275325
DOI: 10.3389/fimmu.2019.01395 -
Stem Cell Reviews and Reports Oct 2017Large articular cartilage defects remain an immense challenge in the field of regenerative medicine because of their poor intrinsic repair capacity. Currently, the... (Review)
Review
Mesenchymal Stem/Progenitor Cells Derived from Articular Cartilage, Synovial Membrane and Synovial Fluid for Cartilage Regeneration: Current Status and Future Perspectives.
Large articular cartilage defects remain an immense challenge in the field of regenerative medicine because of their poor intrinsic repair capacity. Currently, the available medical interventions can relieve clinical symptoms to some extent, but fail to repair the cartilaginous injuries with authentic hyaline cartilage. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stem/progenitor cells with or without scaffolds. Mesenchymal stem/progenitor cells are promising graft cells for tissue regeneration, but the most suitable source of cells for cartilage repair remains controversial. The tissue origin of mesenchymal stem/progenitor cells notably influences the biological properties and therapeutic potential. It is well known that mesenchymal stem/progenitor cells derived from synovial joint tissues exhibit superior chondrogenic ability compared with those derived from non-joint tissues; thus, these cell populations are considered ideal sources for cartilage regeneration. In addition to the progress in research and promising preclinical results, many important research questions must be answered before widespread success in cartilage regeneration is achieved. This review outlines the biology of stem/progenitor cells derived from the articular cartilage, the synovial membrane, and the synovial fluid, including their tissue distribution, function and biological characteristics. Furthermore, preclinical and clinical trials focusing on their applications for cartilage regeneration are summarized, and future research perspectives are discussed.
Topics: Animals; Cartilage, Articular; Cell Differentiation; Cell- and Tissue-Based Therapy; Chondrogenesis; Clinical Trials as Topic; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regeneration; Regenerative Medicine; Synovial Fluid; Synovial Membrane; Tissue Engineering; Wound Healing
PubMed: 28721683
DOI: 10.1007/s12015-017-9753-1 -
Progress in Biophysics and Molecular... Nov 2019This pilot study aimed to investigate the feasibility of non-invasively assessing synovial tissue hypoxia in vivo using photoacoustic (PA) imaging in a post-traumatic... (Review)
Review
OBJECTIVES
This pilot study aimed to investigate the feasibility of non-invasively assessing synovial tissue hypoxia in vivo using photoacoustic (PA) imaging in a post-traumatic osteoarthritis model and explore its correlation with OA severity.
METHODS
The three-dimensional vasculature structure and oxygenation level of synovial tissues of destabilization of the medial meniscus (DMM)-induced osteoarthritis (OA) mice were longitudinally monitored using PA imaging. Vascular volume/tissue volume (%) and tissue oxygen saturation (sO) were validated against results obtained by established Power Doppler (PD) imaging and dynamic changes of inhaled O concentration respectively. PA changes were correlated with the histological grading of cartilage damages.
RESULTS
PA-measurements of vascularity and sO demonstrated a strong correlation with localized blood flow detected by PD imaging (r = 0.506, p < 0.001) and inhaled O concentration. DMM knees exhibited much more vascularity in synovial tissue at 4 months after surgery (median 11.3%, IQR: 10.7-15.5%) than the intact knees at time zero (median:5.1%, IQR:3.8-6.8%, p < 0.001) as well as the sham-operated knees (median: 4%, IQR: 3.75-5.45%, p = 0.017). Paradoxically, synovial tissue sO was significantly lower in DDM knees (median: 37.7%, IQR: 36.4-40.6%) than both the intact (47.1%, IQR: 41.9-49.8% p = 0.001) and sham-operated knees (45.1% IQR: 45.1-52.4%, p = 0.017). The PA-detected synovial tissue hypoxia correlated with the severity of cartilage loss in DMM mice (rho = -0.597, p = 0.031).
CONCLUSION
Here, we demonstrated PA imaging can be implemented for non-invasive imaging of the synovial tissue. Under PA imaging, synovitis in OA was characterized by increased angiogenesis and synovial tissue hypoxia; the latter was associated with the severity of OA.
Topics: Animals; Cartilage, Articular; Cell Hypoxia; Disease Models, Animal; Male; Mice; Molecular Imaging; Osteoarthritis; Oxygen; Photoacoustic Techniques; Synovial Membrane
PubMed: 29601835
DOI: 10.1016/j.pbiomolbio.2018.03.009 -
Immunological Medicine Mar 2022Rheumatoid arthritis (RA) is an autoimmune disease characterized by tumor-like hyperplasia and inflammation of the synovium, which causes synovial cell invasion into the... (Review)
Review
Rheumatoid arthritis (RA) is an autoimmune disease characterized by tumor-like hyperplasia and inflammation of the synovium, which causes synovial cell invasion into the bone and cartilage. In RA pathogenesis, various molecules in effector cells (i.e., immune cells and mesenchymal cells) are dysregulated by genetic and environmental factors. Consistent with the early stages of RA, these pathogenic cells cooperate and activate each other directly by cell-to-cell contact or indirectly humoral factors. Recently, growing evidence has revealed essential role of adipokines, which are multifunctional signal transduction molecules, in the immune system. In this review, we summarize the current understanding of the cross-talk between leptin, one of the most well-known and best-characterized adipokines, and osteoimmunology. Furthermore, we discuss the contribution of leptin to the pathogenesis of RA and its potential mechanisms.
Topics: Arthritis, Rheumatoid; Cartilage; Humans; Inflammation; Leptin; Synovial Membrane
PubMed: 34362290
DOI: 10.1080/25785826.2021.1948689 -
Polish Journal of Pathology : Official... 2022In this study, the immunohistochemical EnVision method was applied to detect CD3, CD4 and CD8 in synovial tissues of 40 patients with rheumatoid arthritis (RA) and 10...
In this study, the immunohistochemical EnVision method was applied to detect CD3, CD4 and CD8 in synovial tissues of 40 patients with rheumatoid arthritis (RA) and 10 patients with osteoarthritis (OA). In 92.5% (37/40) RA cases, lymphocytes were focally aggregated, and even germinal centers appeared, forming lymphoid follicle-like structures. The expression of CD3, CD4, and CD8 were high in synovial tissue of RA group, but low in OA group. The number of CD3, CD4+, and CD8+ lymphocytes in OA group were significantly lower than that in RA group (p < 0.05); CD4+lymphocytes in RA accounted for the majority, and mostly were focally distributed. The number of CD8+lymphocytes in the synovial tissue were small, and were mostly scattered. The number of CD4+lymphocytes were significantly higher than CD8+lymphocytes (p<0.05). Compared with the OA group, the number of CD4+T and CD8+T lymphocytes in RA group were higher, and the ratio of CD4/CD8 was higher in RA group (p < 0.05). In conclusion, the CD3, CD4 and CD8 with high level may promote the occurrence and development of RA. The ratio of CD4+/CD8+ may be used as a reference index for the diagnosis and prognosis of RA.
Topics: Arthritis, Rheumatoid; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Humans; Synovial Membrane
PubMed: 35848477
DOI: 10.5114/pjp.2022.117173 -
Cells Jan 2021This study aimed to investigate the characteristics of exosomes isolated from synovial fluid and their role in osteoclast differentiation in different types of...
This study aimed to investigate the characteristics of exosomes isolated from synovial fluid and their role in osteoclast differentiation in different types of inflammatory arthritis. Exosomes isolated from synovial fluid of rheumatoid arthritis (RA), ankylosing spondylitis (AS), gout, and osteoarthritis (OA) patients were co-incubated with CD14+ mononuclear cells from healthy donors without macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL). Osteoclast differentiation was evaluated via tartrate-resistant acid phosphatase (TRAP) staining and activity and F-actin ring formation. RANKL expression on synovial exosomes was assessed using flow cytometry and an enzyme-linked immunosorbent assay (ELISA). Synovial exosomes were the lowest in OA patients; these induced osteoclastogenesis in the absence of M-CSF and RANKL. Osteoclastogenesis was significantly higher with more exosomes in RA ( = 0.030) than in OA patients, but not in AS or gout patients. On treating macrophages with a specified number of synovial exosomes from RA/AS patients, exosomes induced greater osteoclastogenesis in RA than in AS patients. Synovial exosomal RANKL levels were significantly higher in RA ( = 0.035) than in AS patients. Synovial exosome numbers vary with the type of inflammatory arthritis. Synovial exosomes from RA patients may bear the disease-specific "synovial signature of osteoclastogenesis."
Topics: Arthritis, Rheumatoid; Cell Differentiation; Exosomes; Humans; Inflammation; Osteoclasts; Osteogenesis; RANK Ligand; Synovial Membrane
PubMed: 33435236
DOI: 10.3390/cells10010120 -
Epigenomics Apr 2017Genetic and environmental factors contribute to the risk for rheumatoid arthritis (RA), with epigenetics serving as a possible interface through which risk factors... (Review)
Review
Genetic and environmental factors contribute to the risk for rheumatoid arthritis (RA), with epigenetics serving as a possible interface through which risk factors contribute to RA. High-throughput technologies for interrogating genome and epigenome, and the availability of genetic and epigenetic datasets across a diversity of cell types, enable the identification of candidate causal genetic variants for RA to study their function in core RA processes. To date, RA risk variants were studied in the immune cells but not joint resident cells, for example, synovial fibroblasts. Synovial fibroblasts from different joints are distinct, anatomically specialized cells, defined by joint-specific transcriptomes, epigenomes and phenotypes. Cell type-specific analysis of epigenetic changes, together with genetic fine mapping and interrogation of chromatin 3D interactions may identify new disease relevant pathways, potential therapeutic targets and biomarkers for RA progression or therapy response.
Topics: Arthritis, Rheumatoid; Chromatin; DNA Methylation; Disease Progression; Epigenesis, Genetic; Fibroblasts; Genetic Predisposition to Disease; Genetic Variation; Humans; Synovial Membrane
PubMed: 28322583
DOI: 10.2217/epi-2016-0142 -
Modern Rheumatology Jul 2018Fibroblasts play crucial roles in the pathogenesis of rheumatoid arthritis (RA). Accumulation of fibroblasts in the synovial tissues characterizes the pathology of RA.... (Review)
Review
Fibroblasts play crucial roles in the pathogenesis of rheumatoid arthritis (RA). Accumulation of fibroblasts in the synovial tissues characterizes the pathology of RA. Understanding how fibroblasts accumulate could lead to discovery of new therapeutic targets in RA treatment, while current antirheumatic therapies still have problems in efficacy and safety. In this regard, several studies have revealed cellular origins of fibroblasts in fibrotic tissues in murine models of organ fibrosis. Some studies employed lineage tracing, which bring generally convincing results, using transgenic mice. They demonstrated that resident fibroblasts, pericytes, mesenchymal stem cells, epithelial cells, endothelial cells and bone-marrow-derived and circulating cells can be cellular origins of fibroblasts in organ fibrotic tissues. In this review, we summarize and discuss available evidence for the origins of fibroblasts accumulating in the arthritic synovial tissues and organ fibrotic tissues.
Topics: Animals; Arthritis, Rheumatoid; Fibroblasts; Fibrosis; Humans; Synovial Membrane
PubMed: 29067846
DOI: 10.1080/14397595.2017.1386837 -
Journal of Cellular Physiology Dec 2019Rheumatoid arthritis (RA) is an autoimmune disease, pathologically characterized by lymphocyte infiltration of the synovial membrane that leads to chronic inflammation... (Review)
Review
Rheumatoid arthritis (RA) is an autoimmune disease, pathologically characterized by lymphocyte infiltration of the synovial membrane that leads to chronic inflammation and progressive joint damage. RA develops as a result of increased cell infiltration and cell proliferation as well as impaired cell death. Activated cells in joints including lymphocytes and fibroblast-like synoviocytes (FLS) survive for a long time as a consequence of compromised apoptosis, but the mechanism underlying cell survival in synovium remains to be firmly established. Inhibition of apoptosis by survivin, as a critical antiapoptotic protein, contributes to both the persistence of autoreactive T lymphocytes and tumor-like phenotype of FLS in RA. In addition to the antiapoptotic role, survivin also has prognostic relevance in RA prodromal phase. Hence, this review provides an overview of the current knowledge regarding the involvement of survivin protein in the pathogenesis of RA.
Topics: Animals; Apoptosis; Arthritis, Rheumatoid; Cell Proliferation; Humans; Inflammation; Survivin; Synovial Membrane; Synoviocytes
PubMed: 31062383
DOI: 10.1002/jcp.28784 -
Reumatismo Oct 2018The histopathological and molecular analysis of the synovial tissue has contributed to fundamental advances in our comprehension of arthritis pathogenesis and of the... (Review)
Review
The histopathological and molecular analysis of the synovial tissue has contributed to fundamental advances in our comprehension of arthritis pathogenesis and of the mechanisms of action of currently available treatments. On the other hand, its exploitation in clinical practice for diagnostic or prognostic purposes as well as for the prediction of treatment response to specific disease-modifying anti-rheumatic drugs is still limited. In this review, we present an overview of recent advances in the field of synovial tissue research with specific reference to the methods for synovial tissue collection, approaches to synovial tissue analysis and current perspectives for the exploitation of synovial tissue-derived biomarkers in chronic inflammatory arthritides.
Topics: Antirheumatic Agents; Arthritis; Biomarkers; Biopsy; Chronic Disease; Drug Monitoring; Drug Resistance; Humans; Remission Induction; Rituximab; Synovial Membrane
PubMed: 30282438
DOI: 10.4081/reumatismo.2018.1057