Normal Synovium Research Articles

A4.9 Angiopoietin-like 4 is over–expressed in rheumatoid arthritis: a potential role in pathological bone resorption

Background and ObjectivesIn contrast to normal synovial tissue, rheumatoid synovium is hypoxic, and expresses the hypoxia-inducible transcription factors HIF-1α and HIF-2α which allow the transcription of genes involved in angiogenesis,...

Fibroblast growth factor 2 involved in the pathogenesis of synovial chondromatosis of temporomandibular joint

Synovial chondromatosis (SC) of temporomandibular joint (TMJ) is a rare proliferative disorder characterized by the formation of cartilaginous or osteocartilaginous nodules in synovium and joint space. Fibroblast growth factor 2 (FGF-2) is frequently applied in chondrogenic differentiation assays. Therefore, we hypothesized that FGF-2 might involved in the pathogenesis of SC. SC synovium and loose bodies (LBs) specimens were observed by histological and immunohistochemical methods. Real-time PCR was conducted for comparing genes expressions in SC and normal synovium. SC synoviocytes were stimulated by FGF-2 in the presence or absence of its antagonist long pentraxin-3 (PTX3) for 6days. Real-time PCR and alkaline phosphatase (ALP) activity were performed to examine the effects exerted by FGF-2 and PTX3. SC synovium, no matter facing the articular cavity or covering LB, was characterized by increased quantity of synoviocytes and blood vessels. FGF-2 was expressed in chondrocytes and fibroblast-like cells of LBs, and the wall of blood vessels. Expressions of chondrogenic genes (Sox9 and Wnt-4), osteogenic genes (Foxc2), FGF-2, and VEGF-A mRNA were significantly higher in SC synovium than that of the control group. The stimulation of FGF-2 on SC synoviocytes increased ALP activity and expressions of chondrogenic genes (Sox9, Col2α1, and Aggrecan), osteogenic genes (Foxc2, osteocalcin, and Col1α1), and VEGF-A, but PTX3 inhibited these effects. FGF-2 was responsible for the formation of cartilaginous loose bodies and involved in the pathogenesis of SC.

A preliminary study on the characterization of follicular helper T (Tfh) cells in rheumatoid arthritis synovium

Rheumatoid arthritis (RA) is a chronic and systematic autoimmune inflammatory disease. Recently, a novel T cell subset, follicular helper CD4 T cell (Tfh cells) was found in relation to the pathogenesis and progression of RA, and increased numbers of circulating Tfh cells were found in RA patients. However, there is little evidence regarding the localization of Tfh cells in synovium tissues from RA patients, owing to the lack of an available method to characterize their localization in tissue. The aim of our present study was to characterize the Tfh cells in rheumatoid synovium tissues from RA patients by using immunohistochemistry and triple-fluorescence immunostaining methods. Our results showed that specific staining of CD4, CXCR5 and ICOS could be found on infiltrating immune cells in rheumatoid synovium tissues. The use of triple-fluorescence immunostaining and confocal laser scanning showed immunolocalization of CD4+CXCR5+ICOS+T cells (Tfh cells) in the rheumatoid synovium tissues, whereas these signals were absent in osteoarthritis (OA) synovium and in normal synovium tissues. Thus the data from our present preliminary study support the notion that CD4+CXCR5+ICOS+Tfh cells could be found in rheumatoid synovium tissues from RA patients, indicating the possibility that this T cell subset in synovium tissues may have important roles in the pathogenesis and progression of RA.

Investigation of the immune response to autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses

Mesenchymal stem cells have demonstrated immunomodulatory capabilities as well as modest efficacy in animal models of joint injury, warranting further study as a potential treatment of joint disease. The goal of the study was to investigate the blood and synovial immune and histologic response to intra-articular injection of autologous, allogeneic, and xenogeneic bone marrow-derived mesenchymal stem cells (MSC) in horses. The study group consisted of 6 five-year-old Thoroughbred mares that had been injected previously with 15 million, genetically modified autologous, allogeneic, or xenogeneic MSC into the fetlock joints. One group of autologous cells was genetically modified to permit MSC biolocalization in the synovium. To assess response to the injection, synovial biopsies were obtained via arthroscopy 60 days after MSC injection for gross, histologic and molecular analyses. Peripheral blood mononuclear cells were isolated from each horse 120 days after MSC injection and co-cultured with a monolayer of each MSC group to permit quantification of activated CD4+ lymphocytes and cytokine release (ELISA) upon re-exposure to MSC.Arthroscopic examination revealed normal synovium with no grossly detrimental effect to the synovium or cartilage. Intra-articular MSC produced a persistent mononuclear infiltrate for at least 60 days, mostly perivascular, identified as CD3+ lymphocytes. An immune response (significant increase in CD4+ lymphocytes) was detected upon re-exposure to xenogeneic but not to allogeneic or autologous MSC. An inflammatory cytokine release from peripheral blood mononuclear cell/MSC co-cultures was present in all MSC groups but was significantly greater in the xenogeneic group. In conclusion, intra-articular injection of MSC, regardless of cell origin, incited a persistent mononuclear synovitis demonstrating a sustained biologic influence of these cells. Allogeneic cells did not elicit a detectable immune response upon re-exposure using our methods.

The innervation of synovium of human osteoarthritic joints in comparison with normal rat and sheep synovium

To study whether osteoarthritis (OA) in the knee is associated with a change of the innervation pattern in the synovial layer. In synovial tissue from the normal knee joint of rat and sheep we studied the presence of vessels and of nerve fibres using transmission electron microscopy and immunohistochemistry. Synovial material was also obtained from patients who underwent total knee replacement surgery. This material was examined for inflammatory changes, and the presence of vessels and nerve fibres was assessed. The synovium in the parapatellar region of the normal knee joint of rat and sheep exhibited a dense capillary and neuronal network. It was entered by calcitonin gene-related peptide containing sensory fibres and tyrosine hydroxylase-positive sympathetic nerve fibres. Synovial material from patients with knee OA exhibited different degrees of inflammation. Synovial material without inflammation exhibited a similar vascular and neuronal network as the normal knee joint from rat and sheep. However, in synovium with inflammatory changes we found a significant decrease of nerve fibres in depth ranges close to the synovial lining layer depending on the degree of inflammation whereas deeper regions were less affected. Inflammatory changes in the synovium of OA joints are associated with a massive destruction of the capillary and neuronal network which is present in normal synovium. Due to the disappearance of the sensory fibres it is unlikely that OA pain is initiated directly in the synovium. The loss of normally innervated vascularisation may have multiple consequences for the physiological functions of the synovium.

The Relative Composition of the Inflammatory Infiltrate as an Additional Tool for Synovial Tissue Classification

ObjectivesTraditionally, differences in absolute numbers of cells expressing a certain marker (e.g., positive staining cells per mm2) have been used in immunohistological synovial tissue classification. We have begun to evaluate the relative composition of the inflammatory infiltrates, i.e. percentages of inflammatory cell types in inflammatory infiltrates, as an alternate classification tool that may potentially improve tissue diagnostics, subgrouping in clinical trials, and understanding of pathogenesis of inflammatory and noninflammatory arthropathies.MethodsSynovial tissue specimens (normal synovium, n=15; orthopedic arthropathies, n=6; osteoarthritis, n=26; early undifferentiated arthritis, n=10; rheumatoid arthritis, n=26; chronic septic arthritis, n=11) were stained for CD15, CD68, CD3, CD20, and CD38. Densities of cells expressing a given marker were determined in the superficial subintima. Binary and multicategory receiver operating characteristic (ROC) analysis and naïve Bayes classifier were used to compare the abilities of (1) the absolute densities of cells expressing a given marker (absolute method) with (2) the percentages of these cells in the inflammatory cell population (relative method) to differentiate among the six tissue classes.ResultsThe inflammatory infiltrates in normal synovium and the orthopedic arthropathies consisted almost exclusively of CD68+ and CD3+ cells. Notable fractions of CD20+ and CD38+ cells appeared in a subset of osteoarthritis samples, and increased further in early, rheumatoid and chronic septic arthritis. ROC analyses and naïve Bayes classifier ranked the absolute method above the relative method in terms of overall discriminatory ability. The relative method became slightly superior when the samples were also stratified according to the total number of inflammatory cells/mm2.ConclusionsThis exploratory investigation featuring a variety of joint disorders revealed that measuring the relative proportions of inflammatory cell types may aid in synovial tissue classification if the samples are also stratified according to the intensity of inflammation.

THU0245 Phosphodiesterase 4 Expression in Rheumatoid Arthritis Synovium and Effects of Apremilast on Synovial Fibroblasts

BackgroundApremilast (APR), an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) enzymes, works intracellularly to modulate a network of pro-inflammatory and anti-inflammatory mediators. PDE4 is a cyclic adenosine monophosphate (cAMP)-specific PDE,...

AB0179 An innovative histological classification of rheumatoid synovitis and its relationship to clinical disease activity and joint destruction

BackgroundRheumatoid arthritis (RA) is a heterogeneous disease and subtyping of RA may help optimal therapeutic strategies and outcome prediction. However, there has been no available satisfying classification method till now....

AB0162 Expression of interleukin-20 and its receptor chains IL-20R1, IL-20R2 and IL-22R in synovium from patients with rheumatoid arthritis

BackgroundInterleukin-20 (IL-20) signals via the IL-20R1/IL-20R2 and IL-20R2/IL-22R1 heterodimeric receptor complexes. Elevated expression of IL-20 has been demonstrated in synovial tissue from patients with rheumatoid arthritis (RA). In the rat...

Expression of human beta-defensin-3 in surrounding tissues of infected artificial prostheses

Objective To observe expression of human beta-defensin-3 (HBD-3) in tissues around the infected artificial prostheses and investigate its value in treatment and diagnosis of periprosthetic joint infection (PJI).Methods According to clinical diagnosis,periprosthetic tissues and normal synovial membrane excised in operation were collected and divided into the following four groups:PJI group (n =13),aseptic loosening group (loosening group,n =9),spacer treatment group (treatment group,n =12),and normal group (n =15).HE staining was used to observe infiltration of inflammatory cells.Immunofluorescence staining was used to detect positive cells number and fluorescence intensity.Image-pro plus (IPP) 7.0C software was used to measure the average value of absorbance.Preoperative peripheral white blood cell count,erythrocyte sedimentation rate (ESR),and C-reactive protein (CRP) results were documented.Then,differences of those parameters were analyzed and compared among groups.Results HE staining revealed that all groups had different degree of inflammatory cell infiltration except for normal group.Immunofluorescence staining revealed that the most number of positive cells and highest fluorescence intensity existed in PJI group.Value of absorbance in PJI group was 0.430 ± 0.013,followed by 0.308 ±0.005 in loosening group,0.234 ± 0.009 in treatment group,and 0.089 ± 0.019 in normal group.Preoperative peripheral white blood cell count,ESR and CRP were the highest in PFI group,but were not significantly different among the remaining three groups.Conclusion HBD-3 is highly expressed in tissues around the prostheses which had infection or aseptic loosening,but its expression in response to infection and loosening has difference. Key words: Infection; Joint prosthesis; Defensins; Diagnosis

Influence of TNF-α and biomechanical stress on matrix metalloproteinases and lysyl oxidases expressions in human knee synovial fibroblasts

It was reported that not only ACL but also the synovium may be the major regulator of matrix metalloproteinases (MMPs) in synovial fluids after ACL injury. In order to further confirm whether synovium is capable of regulating the microenvironment in the process of ACL injury, the complicated microenvironment of joint cavity after ACL injury was mimicked and the combined effects of mechanical injury and inflammatory factor [tumour necrosis factor-α (TNF-α)] on expressions of lysyl oxidases (LOXs) and MMPs in synovial fibroblasts derived from normal human synovium were studied. Human normal knee joint synovial fibroblasts were stimulated for 1-6 h with mechanical stretch and inflammatory factor (TNF-α). Total RNA was harvested, reverse transcribed and assessed by real-time polymerase chain reaction for the expression of LOXs and MMP-1, 2, 3 messenger RNAs. MMP-2 activity was assayed from the collected culture media samples using zymography. Compared to control group, our results showed that 6% physiological stretch increased MMP-2 and LOXs (except LOXL-3), decreased MMP-1 and MMP-3; injurious stretch (12%) decreased LOXs (except LOXL-2)and increased MMP-1, 2 and 3; the combination of injurious stretch and TNF-α decreased LOXs and increased MMP-1, 2 and 3 in synovial fibroblasts in a synergistical manner. This study demonstrated that combination of mechanical injury and inflammatory factors up-regulated the expressions of MMPs and down-regulated the expressions of LOXs in synovial fibroblasts, eventually alter the balance of tissue healing. Thus, synovium may be involved in regulating the microenvironment of joint cavity. Based on the mechanism, early interventions to inhibit the production of MMPs or promote the production of LOXs in the synovial fibroblasts should be performed to facilitate the healing of tissue.

Synoviocytes protect cartilage from the effects of injury in vitro

BackgroundIt is well documented that osteoarthritis (OA) can develop following traumatic joint injury and is the leading cause of lameness and subsequent wastage of equine athletes. Although much research of injury induced OA has focused on cartilage, OA is a disease that affects the whole joint organ.MethodsIn this study, we investigated the impact of synovial cells on the progression of an OA phenotype in injured articular cartilage. Injured and control cartilage were cultured in the presence of synoviocytes extracted from normal equine synovium. Synoviocytes and cartilage were evaluated for catabolic and anabolic gene expression. The cartilage was also evaluated histologically for loss of extracellular matrix molecules, chondrocyte cell death and chondrocyte cluster formation.ResultsThe results indicate synoviocytes exert both positive and negative effects on injured cartilage, but ultimately protect injured cartilage from progressing toward an OA phenotype. Synoviocytes cultured in the presence of injured cartilage had significantly reduced expression of aggrecanase 1 and 2 (ADAMTS4 and 5), but also had increased expression of matrix metalloproteinase (MMP) -1 and reduced expression of tissue inhibitor of metalloproteinases 1 (TIMP-1). Injured cartilage cultured with synoviocytes had increased expression of both collagen type 2 and aggrecanase 2. Histologic examination of cartilage indicated that there was a protective effect of synoviocytes on injured cartilage by reducing the incidence of both focal cell loss and chondrocyte cluster formation, two major hallmarks of OA.ConclusionsThese results support the importance of evaluating more than one synovial joint tissue when investigating injury induced OA.

Abundant LacZ activity in the absence of Cre expression in the normal and inflamed synovium of adult Col2a1-Cre; ROSA26RLacZ reporter mice

Recent analyses of Col2a1-Cre; ROSA26R reporter mice showed that synovial fibroblasts in 7-day mice were LacZ positive, due to a history of Col2a1-Cre expression conferred by their origin in the interzone of the developing joint. We have examined LacZ staining in adult Col2a1-Cre(+/0); ROSA26R(LacZ) mice, with and without inflammatory arthritis, and found that synovial fibroblasts in normal and inflamed synovium are LacZ positive, but Cre negative. Our results suggest that Cre-mediated recombination in joint interzone cells during development endure in adult synovial cells despite the absence of ongoing Cre expression. These findings have important implications and applications for the study of synovial inflammation in models of experimental arthritis.

Podoplanin (D2-40) and Clusterin Are Reliable Markers of Normal and Inflamed Synovium

Synovial lining cells (“intima”) arise from a proliferation of fibroblast-like cells and recruitment of macrophage-like cells from the circulation. Recent work has shown that synovial intimal cells are positive for clusterin (CLU) and podoplanin (PP). CLU has been noted to mark nonneoplastic synovium adjacent to tenosynovial tumors, and some studies suggest that PP …

Sensory innervation and inflammatory cytokines in hypertrophic synovia associated with pain transmission in osteoarthritis of the hip: a case-control study

To clarify the sensory innervation and inflammatory cytokines in hypertrophic synovia associated with pain transmission in OA of the hip. A piece of the synovium was extracted during reconstruction surgery in 50 patients with OA of the hip as an inflammatory synovium and in 12 patients with femoral neck fracture as a normal synovium. Each sample was immersed in fixative solution, sectioned on a cryostat, and then processed for immunohistochemistry using antibodies as follows: neuron-specific class III β-tubulin (TuJ-1) as a general marker for nerve fibres, calcitonin gene-related peptide (CGRP) for sensory nerve fibres, nuclear factor κB (NF-κB) for the protein complex controlling the transcription of DNA in cellular responses to painful stimuli, and TNF-α for cytokines involved in acute inflammation. The number of immunopositive cells and fibres were counted using a fluorescence microscope. In the inflammatory synovium of OA of the hip, TuJ-1 was positive in 46% (23 hips). Of those positive for TuJ-1, 78% (18 hips) were also positive for CGRP, but 22% (5 hips) were negative for CGRP. NF-κB was positive in 68% (34 hips). Of those positive for NF-κB, 76% (26 hips) were also positive for TNF-α, but 24% (8 hips) were negative for TNF-α. In normal synovia, all four substances were negative. We suggest sensory innervation and inflammatory cytokines in hypertrophic synovia are associated with nociception in OA of the hip. University Hospital Medical Information Network, www.umin.ac.jp, UMIN000001335.

A role for the sensory neuropeptide calcitonin gene‐related peptide in endothelial cell proliferation in vivo

We have tested the hypothesis that calcitonin gene-related peptide (CGRP) is a mediator of capsaicin-induced angiogenesis in vivo. In a series of experiments, the knee joints of rats were injected with CGRP, capsaicin or vehicle control. Groups of animals (n=6) were treated with the CGRP receptor antagonist BIBN4096BS and/or the NK₁ receptor antagonist SR140333. Endothelium, proliferating endothelial cell nuclei and macrophages were identified 24 h later in the synovium by immunohistochemistry and quantified by image analysis. mRNA for the receptors for CGRP and adrenomedullin were sought in normal and inflamed rat and human synovia using RT-PCR. Intra-articular CGRP injection increased the endothelial cell proliferation index, whereas macrophage infiltration and knee joint diameters were similar to saline-injected controls. CGRP-induced endothelial cell proliferation was dose-dependently inhibited by BIBN4096BS. mRNA for adrenomedullin and the CGRP receptor subunits were detected in normal and inflamed human and rat synovia. In capsaicin-induced synovitis, the increased endothelial cell proliferation index was partially blocked by administration of NK₁ or CGRP antagonists individually and was reduced to the level of saline controls by coadministration of both receptor antagonists. These data support the hypothesis that CGRP stimulates angiogenesis in vivo directly by activating CGRP receptors. Capsaicin-induced endothelial cell proliferation was completely blocked by coadministration of CGRP and NK₁ receptor antagonists, indicating that both CGRP and substance P may contribute to angiogenesis in this model of synovitis.

Human osteoarthritis synovium contains an alternatively spliced transcript of ADAMTS4

Purpose: The characterization of an alternatively spliced transcript of the ADAMTS4 aggrecanase. Methods: In human OA synovial cell cultures, RT-PCR was performed using oligonucleotide primers designed to amplify across the exon 8/9 region of human ADAMTS4. The PCR products were purified using a QIAquick purification kit (Qiagen) and sequenced using in house facilities. A pCEP4 (Invitrogen) mammalian expression vector containing ADAMTS4 plus a FLAG epitope was mutated using the QuikChange II site directed mutagenesis kit (Stratagene) to contain the ADAMTS4 splice variant plus a FLAG epitope. The recombinant proteins were purified from HEK293 transfected cells using Anti-FLAG M2 affinity gel (Sigma). Polyclonal antibodies were raised against synthetic peptides representing sequences within the C-terminal region of the splice variant of ADAMTS4 and the raised antibodies were characterized using the recombinant splice variant of ADAMTS4. The antibodies were used in immunohistochemical analysis of human osteoarthritic synovium. The proteolysis of aggrecan and other proteoglycans by the recombinant spice variant of ADAMTS4 was investigated. Results: The degradation of aggrecan is mainly mediated by the aggrecanases, of which ADAMTS4 (aggrecanase-1) and ADAMTS5 (aggrecanase-2) are the best known. We here characterize an alternative splice variant of ADAMTS4. RT-PCR performed as described above resulted in the amplification of normal ADAMTS4, and also a smaller product missing 161 base pairs from the 5’ end of exon 9, the result of alternative splicing in which exon 8 joins to a cryptic 3’ splice site within exon 9. The protein produced by this alternative splicing would lack the spacer domain and have a C-terminus lacking any homologies with the normal ADAMTS4 spacer domain. The alternatively spliced transcript of ADAMTS4 was found in cultured OA synovial cells and in freshly digested OA synovium, but not in human brain, cervix or lung, or in normal bovine synovium. The protein synthesized from this alternatively spliced transcript of ADAMTS4 would lose functions dependent on its spacer domain, like substrate and matrix binding, and inhibition through fibronectin. Removal of the spacer domain from ADAMTS4 has been reported to increase its ability to cleave aggrecan at the Glu373-Ala374 bond, and it may well be that the alternatively spliced transcript produces a protein that is secreted in a more active form. HEK293 cells transfected with a pCEP4 vector containing the cDNA sequence of the splice variant of ADAMTS4 produced the corresponding protein in both the pro and active form. This protein could be found in the media, but mostly associated with the cells, as confirmed using antibodies specific for the splice variant that were produced using synthetic peptides. Immunohistochemical analysis of osteoarthritic synovium using these antibodies showed staining of cells within the synovium. Proteins purified by immunoprecipitation by Anti-FLAG M2 affinity gel from transfected and untransfected HEK293 cells were analysed using the ANASpec SensoLyte 520 Aggrecanase I assay kit. The splice variant had aggrecanase activity comparable to a commercially available ADAMTS4. The splice variant cleaved aggrecan at the G1u373-A1a374 site, as assessed by the neoepitope monoclonal antibody BC3, with activity comparable to ADAMTS4. Conclusions: ADAMTS4 is regulated at multiple levels through control of gene expression, mRNA splicing and protein processing, as well as the expression of naturally occurring inhibitors. We here describe the characteristics of the first known splice variant of ADAMTS4. This alternative splice transcript of ADAMTS4 is expressed as a protein in vivo and can be found in the synovium. It can be speculated that the changes in the C-terminal domain of the protein resulting from this alternatively spliced transcript would have changes in its substrate specificity. The protein produced by the alternative spliced transcript of ADAMTS4 has aggrecanase activity, and the release of low levels of this fully active variant of ADAMTS4 might be a factor in the slow process of superficial zone aggrecan loss in osteoarthritis.

CXCL12γ isoform is expressed on endothelial and dendritic cells in rheumatoid arthritis synovium and regulates T cell activation

CXCL12γ is an alternative splicing isoform of CXCL12 with enhanced affinity for heparan sulfate (HS) proteoglycans. This study was undertaken to investigate the distribution and potential function of CXCL12γ in rheumatoid arthritis (RA) synovium and normal lymphoid tissue, where its immobilization to HS may be relevant in pathologic or homeostatic immune cell migration and activation. Expression of CXCL12 or CXCL12γ was immunodetected in RA and normal synovium, lymphoid tissue, and cultured cells with anti-pan-CXCL12 or anti-CXCL12γ-specific monoclonal antibodies. CXCL12α and CXCL12γ messenger RNA expression was analyzed by quantitative reverse transcription-polymerase chain reaction. Binding of wild-type CXCL12 isoforms or their HS binding-defective mutants to monocyte-derived dendritic cells (DCs) was analyzed by flow cytometry. The effect of DC-bound CXCL12α and CXCL12γ on T cell activation was analyzed in DC/T cell allogeneic cultures. CXCL12γ expression was increased in RA compared to normal synovium and preferentially located in endothelia and DC-SIGN-positive cells. This distribution was also observed in lymphoid organs. Surface-bound CXCL12γ was detected in a fraction of freshly isolated DCs. Monocyte-derived DCs, but not monocytes, showed a high capacity to bind CXCL12γ in an HS-dependent manner. Surface-bound CXCL12α and CXCL12γ on monocyte-derived DCs were potent inhibitors of allogeneic T cell activation, in contrast to the T cell-stimulatory effects of soluble CXCL12 proteins. CXCL12γ shows a specific and similar distribution in RA synovium and lymphoid tissue, consistent with its higher HS binding affinity. Presentation of CXCL12 to T cells on membrane HS in DCs can play a distinct regulatory role in T cell activation.

Synovial Sarcoma In The Anterior Abdominal Wall Of A Young Nigerian Female: Case Report.

Synovial sarcoma is a malignant mesenchymal neoplasm so named after its microscopic resemblance to normal synovium. Large joints of the extremities are the most common site and, rarely, the tumor may be found in the anterior abdominal wall. We report a case of synovial sarcoma in the right upper quadrant of the anterior abdominal wall of a 21-year-old Nigerian female. The patient underwent surgical excision with clear margins and the histological and immunohistochemical studies confirmed a monophasic synovial sarcoma.

The Normal Synovium

This paper describes the structure and function of the normal synovium including the cellular content, nerve and vascular supply and how normal synovium maintains homeostasis within the joint. It is important to understand normal synovium before appreciating the changes that occur in the synovial membrane which leads to the pathology seen in inflammatory arthritides such as Rheumatoid Arthritis.