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Journal of Anatomy Mar 2016The lining layer of the synovial membrane in the temporomandibular joint (TMJ) contains two types of lining cells: macrophage-like type A and fibroblast-like type B...
The lining layer of the synovial membrane in the temporomandibular joint (TMJ) contains two types of lining cells: macrophage-like type A and fibroblast-like type B cells. The type B cells are particularly heterogeneous in their morphology and immunoreactivity, so that details of their functions remain unclear. Some of the type B cells exhibit certain resemblances in their ultrastructure to those of an activated capillary pericyte at the initial stage of the angiogenesis. The articular surface, composed of cartilage and the disc in the TMJ, has few vasculatures, whereas the synovial lining layer is richly equipped with blood capillaries to produce the constituent of synovial fluid. The present study investigated at both the light and electron microscopic levels the immunocytochemical characteristics of the synovial lining cells in the adult rat TMJ, focusing on their contribution to the synovial vascularization. It also employed an intravascular perfusion with Lycopersicon esculentum (tomato) lectin to identify functional vessels in vivo. Results showed that several type B cells expressed desmin, a muscle-specific intermediate filament which is known as the earliest protein to appear during myogenesis as well as being a marker for the immature capillary pericyte. These desmin-positive type B cells showed immunoreactions for vimentin and pericyte markers (neuron-glial 2; NG2 and PDGFRβ) but not for the other markers of myogenic cells (MyoD and myogenin) or a contractile apparatus (αSMA and caldesmon). Immunoreactivity for RECA-1, an endothelial marker, was observed in the macrophage-like type A cells. The arterioles and venules inside the synovial folds extended numerous capillaries with RECA-1-positive endothelial cells and desmin-positive pericytes to distribute densely in the lining layer. The distal portion of these capillaries showing RECA-1-immunoreactivity lacked lectin-staining, indicating a loss of blood-circulation due to sprouting or termination in the lining layer. The desmin-positive type B and RECA-1-positive type A cells attached to this portion of the capillaries. Some capillaries in the lining layer also expressed ninein, a marker for sprouting endothelial cells, called tip cells. Since an activated pericyte, macrophage and tip cell are known to act together at the forefront of the vessel sprout during angiogenesis, the desmin-positive type B cell and RECA-1-positive type A cell might serve as these angiogenic cells in the synovial lining layer. Tomato lectin perfusion following decalcification would be a highly useful tool for research on the vasculature of the mineralized tissue. Use of this technique combined with immunohistochemistry should permit future extensive investigations on the presence of the physiological angiogenesis and on the function of the lining cells in the synovial membrane.
Topics: Animals; Immunohistochemistry; Male; Microscopy, Electron; Rats; Rats, Wistar; Synovial Membrane; Temporomandibular Joint
PubMed: 26642772
DOI: 10.1111/joa.12426 -
Annals of the Rheumatic Diseases Nov 1999To define the pattern of mRNA expression of all human matrix metalloproteinases (MMPs) described to date in rheumatoid arthritis (RA) and traumatic synovial membrane, in... (Comparative Study)
Comparative Study
OBJECTIVE
To define the pattern of mRNA expression of all human matrix metalloproteinases (MMPs) described to date in rheumatoid arthritis (RA) and traumatic synovial membrane, in order to differentiate between a physiological tissue remodelling pattern and that associated with inflammatory tissue destruction.
METHODS
Analysis of SwissProt protein and EMBL/GenBank nucleotide sequence banks, protein sequence alignment, reverse transcriptase-polymerase chain reaction and nucleotide sequencing were used.
RESULTS
MMP-2 (gelatinase A), MMP-3 (stromelysin-1), MMP-11 (stromelysin-3) and MMP-19 were constitutively expressed. MMP-1 (fibroblast type collagenase), MMP-9 (gelatinase B) and MMP-14 (MT1-MMP) were expressed in all RA, but only in 55-80% of trauma samples. MMP-13 (collagenase-3) and MMP-15 (MT2-MMP) were expressed exclusively in RA (80-90% of the samples). MMP-20 (enamelysin) was absent and MMP-8 (collagenase-2) was rarely found in RA or trauma. All other MMPs (-7, -10, -12, -16, -17) had an intermediate pattern of expression.
CONCLUSIONS
Some MMPs without interstitial collagenase activity seem to have a constitutive pattern of expression and probably participate in physiological synovial tissue remodelling. Some MMPs are exclusively associated to RA synovitis, for example, MMP-13, which preferentially degrades type II collagen and aggrecan, and MMP-15, which activates proMMP-2 and proMMP-13 and is involved in tumour necrosis factor alpha processing. This clear cut rheumatoid/inflammatory MMP profile, more complex than has been previously appreciated, may facilitate inflammatory tissue destruction in RA.
Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Female; Gene Expression; Humans; Male; Matrix Metalloproteinases; Middle Aged; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Synovial Membrane
PubMed: 10531073
DOI: 10.1136/ard.58.11.691 -
Arthritis and Rheumatism May 1999To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Magnetic resonance imaging-determined synovial membrane volume as a marker of disease activity and a predictor of progressive joint destruction in the wrists of patients with rheumatoid arthritis.
OBJECTIVE
To evaluate the synovial membrane volume, determined by magnetic resonance imaging (MRI), as a marker of joint disease activity and a predictor of progressive joint destruction in rheumatoid arthritis (RA).
METHODS
Twenty-six patients with RA, randomized to receive disease-modifying antirheumatic drug (DMARD) therapy alone (11 patients) or DMARDs in combination with oral prednisolone (15 patients), were followed up for 1 year with contrast-enhanced MRI of the dominant wrist (months 0, 3, 6, and 12), conventional radiography (months 0 and 12), and clinical and biochemical examinations. Bone erosion (by MRI and radiography) and synovial membrane volumes (by MRI) were assessed.
RESULTS
Significant synovial membrane volume reductions were observed after 3 and 6 months in the DMARD + prednisolone group, and after 6 and 12 months in the DMARD-alone group (P < 0.01-0.02, by Wilcoxon-Pratt analysis). The rate of erosive progression on MRI was highly correlated with baseline scores and, particularly, with area under the curve (AUC) values of synovial membrane volume (Spearman's sigma = 0.69, P < 0.001), but not with baseline or AUC values of local or global clinical or biochemical parameters, or with prednisolone treatment. In none of 5 wrists with baseline volumes <5 cm3, but in 8 of 10 wrists with baseline volumes > or =10 cm3, erosive progression was found by MRI and/or radiography, indicating a predictive value of synovial membrane volumes. MRI was more sensitive than radiography for the detection of progressive bone destruction (22 versus 12 new bone erosions).
CONCLUSION
MRI-determined synovial membrane volumes are closely related to the rate of progressive joint destruction. Quantitative MRI assessment of synovitis may prove valuable as a marker of joint disease activity and a predictor of progressive joint destruction in RA.
Topics: Administration, Oral; Adult; Aged; Arthritis, Rheumatoid; Humans; Hypertrophy; Longitudinal Studies; Magnetic Resonance Imaging; Middle Aged; Observer Variation; Prednisolone; Prognosis; Radiography; Synovial Membrane; Wrist Joint
PubMed: 10323447
DOI: 10.1002/1529-0131(199905)42:5<918::AID-ANR10>3.0.CO;2-2 -
Mediators of Inflammation 2013Rheumatoid arthritis is a chronic inflammatory disease characterized by synovial hyperplasia and progressive joint destruction. The impaired apoptosis of rheumatoid... (Review)
Review
Rheumatoid arthritis is a chronic inflammatory disease characterized by synovial hyperplasia and progressive joint destruction. The impaired apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) is pivotal in this process. However, the molecular mechanisms responsible for the reduced apoptosis are not fully understood. Both nitric oxide and thioredoxin 1 as two important mediators are widely investigated in the pathogenesis of rheumatoid arthritis. Interestingly, studies have showed that thioredoxin 1 may serve as a master regulator of S-nitrosylation of caspase-3 to fine-tune apoptosis in vivo. Thus, it is anticipated that further investigations on the role of thioredoxin 1 in the S-nitrosylation and denitrosylation of caspase-3 in RA-FLS will likely provide a novel understanding of mechanisms implicated in the impaired apoptosis of RA-FLS. In this paper, we will provide an overview on pathways involved in the reduced apoptosis of RA-FLS and then discuss specially the possible roles of nitric oxide and the thioredoxin 1 redox system associated with apoptosis of RA-FLS.
Topics: Animals; Apoptosis; Arthritis, Rheumatoid; Humans; Nitric Oxide; Synovial Membrane; Thioredoxins
PubMed: 23690674
DOI: 10.1155/2013/953462 -
Folia Histochemica Et Cytobiologica 2007The objective of this work was to devise an in vitro system for studies on cytokine secretion by synovial membrane treated as a whole organ with various synoviocyte...
The objective of this work was to devise an in vitro system for studies on cytokine secretion by synovial membrane treated as a whole organ with various synoviocyte populations. Synovial membrane from knee joints of WAG rats was dissected and incubated in culture medium without serum for 4 - 48 h. The level of IL-1alpha was determined in synovial lysates and IL-6 in culture medium. The synovial membrane from left and right knee joint of the same rat produced similar amount of cytokines both in lysates and in the medium. Synovial membrane stimulated by LPS for 4 or 24 h gave significantly stronger cytokine response than the membrane from the opposite (control) knee. After 48 h incubation of synovial membrane drastic drop in cytokine level was noted, which indicated on deterioration of the membranes. The test may be useful in studies on factors affecting cytokine secretion by synoviocytes.
Topics: Animals; Culture Media, Serum-Free; Immunohistochemistry; Interleukin-1alpha; Interleukin-6; Lipopolysaccharides; Rats; Rats, Wistar; Synovial Fluid; Synovial Membrane; Synovitis
PubMed: 17378248
DOI: No ID Found -
Arthritis and Rheumatism Mar 2010To define the intrinsic capacity of fibroblast-like synoviocytes (FLS) to establish a 3-dimensional (3-D) complex synovial lining architecture characterized by the...
OBJECTIVE
To define the intrinsic capacity of fibroblast-like synoviocytes (FLS) to establish a 3-dimensional (3-D) complex synovial lining architecture characterized by the multicellular organization of the compacted synovial lining and the elaboration of synovial fluid constituents.
METHODS
FLS were cultured in spherical extracellular matrix (ECM) micromasses for 3 weeks. The FLS micromass architecture was assessed histologically and compared with that of dermal fibroblast controls. Lubricin synthesis was measured via immunodetection. Basement membrane matrix and reticular fiber stains were performed to examine ECM organization. Primary human and mouse monocytes were prepared and cocultured with FLS in micromass to investigate cocompaction in the lining architecture. Cytokine stimuli were applied to determine the capacity for inflammatory architecture rearrangement.
RESULTS
FLS, but not dermal fibroblasts, spontaneously formed a compacted lining architecture over 3 weeks in the 3-D ECM micromass organ cultures. These lining cells produced lubricin. FLS rearranged their surrounding ECM into a complex architecture resembling the synovial lining and supported the survival and cocompaction of monocyte/macrophages in the neo-lining structure. Furthermore, when stimulated by cytokines, FLS lining structures displayed features of the hyperplastic rheumatoid arthritis synovial lining.
CONCLUSION
This 3-D micromass organ culture method demonstrates that many of the phenotypic characteristics of the normal and the hyperplastic synovial lining in vivo are intrinsic functions of FLS. Moreover, FLS promote survival and cocompaction of primary monocytes in a manner remarkably similar to that of synovial lining macrophages. These findings provide new insight into inherent functions of the FLS lineage and establish a powerful in vitro method for further investigation of this lineage.
Topics: Animals; Extracellular Matrix; Fibroblasts; Glycoproteins; Humans; Inflammation; Macrophages; Mice; Organ Culture Techniques; Synovial Fluid; Synovial Membrane
PubMed: 20131230
DOI: 10.1002/art.27285 -
Journal of Anatomy Jun 1994Synovium is characterised by an intimal layer of cells, now recognised to be a mixture of bone marrow-derived macrophages and specialised fibroblast-like cells. The... (Review)
Review
Synovium is characterised by an intimal layer of cells, now recognised to be a mixture of bone marrow-derived macrophages and specialised fibroblast-like cells. The fibroblast-like cells, or synoviocytes, differ from other fibroblasts in a number of respects, including high activity of uridine diphosphoglucose dehydrogenase (UDPGD) and constitutive expression of VCAM-1. Experiments have been devised to try to establish the factors that control these specialised features. Both high UDPGD activity and VCAM-1 expression can be seen in adventitious or regenerate connective tissue linings tissue under certain circumstances. Mechanical factors may be implicated in the induction of UDPGD activity and VCAM-1 expression, but there is evidence that they are controlled independently. The factors involved in synoviocyte differentiation both in the embryo and under conditions of regeneration or generation ab initio at adventitious sites in the adult require further investigation.
Topics: Cell Differentiation; Humans; Macrophages; Synovial Membrane; Uridine Diphosphate Glucose Dehydrogenase
PubMed: 7928638
DOI: No ID Found -
International Journal of Molecular... Nov 2021Fetal cartilage fully regenerates following injury, while in adult mammals cartilage injury leads to osteoarthritis (OA). Thus, in this study, we compared the in vivo...
Fetal cartilage fully regenerates following injury, while in adult mammals cartilage injury leads to osteoarthritis (OA). Thus, in this study, we compared the in vivo injury response of fetal and adult ovine articular cartilage histologically and proteomically to identify key factors of fetal regeneration. In addition, we compared the secretome of fetal ovine mesenchymal stem cells (MSCs) in vitro with injured fetal cartilage to identify potential MSC-derived therapeutic factors. Cartilage injury caused massive cellular changes in the synovial membrane, with macrophages dominating the fetal, and neutrophils the adult, synovial cellular infiltrate. Correspondingly, proteomics revealed differential regulation of pro- and anti-inflammatory mediators and growth-factors between adult and fetal joints. Neutrophil-related proteins and acute phase proteins were the two major upregulated protein groups in adult compared to fetal cartilage following injury. In contrast, several immunomodulating proteins and growth factors were expressed significantly higher in the fetus than the adult. Comparison of the in vitro MSCs proteome with the in vivo fetal regenerative signature revealed shared upregulation of 17 proteins, suggesting their therapeutic potential. Biomimicry of the fetal paracrine signature to reprogram macrophages and modulate inflammation could be an important future research direction for developing novel therapeutics.
Topics: Acute-Phase Proteins; Animals; Cartilage, Articular; Cell- and Tissue-Based Therapy; Cells, Cultured; Fetus; Macrophages; Mesenchymal Stem Cells; Neutrophils; Osteoarthritis; Regeneration; Sheep; Synovial Membrane
PubMed: 34884768
DOI: 10.3390/ijms222312969 -
Neuroscience Oct 2014Vitamin D deficiency is associated with increased susceptibility to inflammatory arthritis. Sensory and sympathetic synovial nerves are critical to the development of...
Vitamin D deficiency is associated with increased susceptibility to inflammatory arthritis. Sensory and sympathetic synovial nerves are critical to the development of inflammatory arthritis and spontaneously degenerate in the early phases of disease. These nerves contain vitamin D receptors and vitamin D influences nerve growth and neurotrophin expression. We therefore examined the density of synovial nerves and neurotrophin-containing cells in vitamin D-deficient rats. Seven-week-old Sprague-Dawley rats were fed either control or vitamin D-deficient diets for 4weeks. Knee synovium sections extending from the patella to the meniscus were immunostained for total nerves, myelinated and unmyelinated nerves, sympathetic nerves, peptidergic and non-peptidergic sensory nerves, and neurotrophins and immune cell markers. In control rats, intimal innervation by unmyelinated sensory fibers was denser than subintimal innervation. In contrast, sympathetic innervation was confined to the subintima. Many sensory axons contained markers for both peptidergic and non-peptidergic nerves. Nerve growth factor (NGF) was primarily expressed by intimal CD163-negative type B synoviocytes, while neurturin, a ligand selective for non-peptidergic sensory neurons, was expressed by synovial mast cells. In vitamin D-deficient rats, there were significant reductions in sensory nerves in the intima and sympathetic nerves in the subintima. While there was no significant change in NGF-immunoreactivity, the number of neurturin-expressing mast cells was significantly reduced in the intima, suggesting that intimal reductions in sensory nerves may be related to reductions in neurturin. Vitamin D deficiency therefore may increase susceptibility to inflammatory arthritis by depleting sensory and sympathetic synovial nerves as a result of reduced synovial neurotrophin content.
Topics: Animals; Cell Count; Female; Knee Joint; Mast Cells; Microscopy, Confocal; Nerve Growth Factor; Neurturin; Random Allocation; Rats, Sprague-Dawley; Sensory Receptor Cells; Synovial Membrane; Vitamin D Deficiency
PubMed: 25193239
DOI: 10.1016/j.neuroscience.2014.08.035 -
The Western Journal of Medicine Nov 1996
Topics: Humans; Joint Diseases; Radioisotopes; Synovial Membrane
PubMed: 8993201
DOI: No ID Found