Enhance and Maintain Chondrogenesis of Synovial Fibroblasts by Cartilage Extracellular Matrix Protein Matrilins

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Pei, Ming; Luo, Junming; Chen, Qian

2008-01-01

Summary Objective Cartilage-specific extracellular matrix (ECM) proteins have been proposed to play key roles in modulating cellular phenotypes during chondrogenesis of mesenchymal stem cells. Matrilin (MATN) 1 and 3 are among the most up-regulated ECM proteins during chondrogenesis. The aim of this study was to analyze their roles in chondrogenesis of mesenchymal fibroblasts from synovium. Methods Primary synovial fibroblasts (SFBs) were purified from porcine synovium and incubated in pellet culture for 18 days. Chondrogenesis of SFB was analyzed by histological staining with safranin-O/fast green, and by quantifying glycosaminoglycans with dimethylmethylene blue assay. The mRNA levels of chondrogenic markers including collagen II, aggrecan, and Sox 9 were quantified by real-time RT-PCR, while the protein levels of Col II and matrilins were determined by western blot analysis. Results SFBs underwent chondrogenesis after incubation with TGF-β1 for three days; however, this process was attenuated during the subsequent incubation period. Expression of a MATN1 or 3 cDNA maintained and further enhanced chondrogenesis of SFBs as shown by increased cartilaginous matrix areas, elevated amount of glycosaminoglycans, and stimulated expression of chondrogenic markers. Conclusion Our findings suggest a novel function for MATN1 and 3 to maintain and enhance chondrogenesis of mesenchymal fibroblasts initiated by TGF-β. Our results also support a critical role of cartilage-specific ECM proteins to modulate cellular phenotypes in the microenvironment during chondrogenic differentiation. PMID:18282772

Enhancing and maintaining chondrogenesis of synovial fibroblasts by cartilage extracellular matrix protein matrilins.

Science.gov (United States)

Pei, M; Luo, J; Chen, Q

2008-09-01

Cartilage-specific extracellular matrix (ECM) proteins have been proposed to play key roles in modulating cellular phenotypes during chondrogenesis of mesenchymal stem cells. Matrilin (MATN)1 and MATN3 are among the most up-regulated ECM proteins during chondrogenesis. The aim of this study was to analyze their roles in chondrogenesis of mesenchymal fibroblasts from synovium. Primary synovial fibroblasts (SFBs) were purified from porcine synovium and incubated in pellet culture for 18 days. Chondrogenesis of SFB was analyzed by histological staining with safranin-O/fast green, and by quantifying glycosaminoglycans (GAG) with dimethylmethylene blue assay. The mRNA levels of chondrogenic markers including collagen II, aggrecan, and Sox 9 were quantified by real-time reverse transcription polymerase chain reaction, while the protein levels of Col II and MATNs were determined by western blot analysis. SFBs underwent chondrogenesis after incubation with transforming growth factor-beta1 (TGF-beta1) for 3 days; however, this process was attenuated during the subsequent incubation period. Expression of a Matn1 or Matn3 cDNA maintained and further enhanced chondrogenesis of SFBs as shown by increased cartilaginous matrix areas, elevated amount of GAG, and stimulated expression of chondrogenic markers. Our findings suggest a novel function for MATN1 and MATN3 to maintain and enhance chondrogenesis of mesenchymal fibroblasts initiated by TGF-beta. Our results also support a critical role of cartilage-specific ECM proteins to modulate cellular phenotypes in the microenvironment during chondrogenic differentiation.

Basic calcium phosphate crystal-induced Egr-1 expression stimulates mitogenesis in human fibroblasts

International Nuclear Information System (INIS)

Zeng, Xiao R.; Sun Yubo; Wenger, Leonor; Cheung, Herman S.

2005-01-01

Previously, we have reported that basic calcium phosphate (BCP) crystals stimulate mitogenesis and synthesis of matrix metalloproteinases in cultured human foreskin and synovial fibroblasts. However, the detailed mechanisms involved are still unclear. In the present study, using RT-PCR and Egr-1 promoter analysis we showed that BCP crystals could stimulate early growth response gene Egr-1 transcription through a PKCα-dependent p44/p42 MAPK pathway. Using a retrovirus gene expression system (Clontech) to overexpress Egr-1 in human fibroblast BJ-1 cells resulted in promotion of mitogenesis measured either by MTT cell proliferation analysis or by direct cell counting. The results demonstrate that Egr-1 may play a key role in mediating BCP crystal-induced synovial fibroblast mitogenesis

Expression and Functions of Immediate Early Response Gene X-1 (IEX-1 in Rheumatoid Arthritis Synovial Fibroblasts.

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Akio Morinobu

Full Text Available In rheumatoid arthritis (RA, synovial fibroblasts (RA-SFs accumulate in affected joints, where they play roles in inflammation and joint destruction. RA-SFs exhibit tumor-like proliferation and are resistant to apoptosis. Although RA-SF activation is well described, negative regulators of RA-SF activation are unknown. We previously reported that histone deacetylase (HDAC inhibitors facilitate apoptosis in RA-SFs. Here we found that RA-SFs treated with the HDAC inhibitor Trichostatin A (TSA exhibited an upregulation of the immediate early response gene X-1 (IEX-1. IEX-1 has roles in apoptosis sensitivity, cell-cycle progression, and proliferation, and is reported to be involved in immune responses, inflammation, and tumorigenesis, and to have anti-arthritic properties. To investigate IEX-1's role in RA-SFs, we used in vitro-cultured synovial fibroblasts from RA and osteoarthritis (OA patients. We confirmed that TSA upregulated the IEX-1 protein and mRNA expressions in RA-SFs by western blotting and quantitative RT-PCR. Inhibiting HDAC1, 2, and 3 (but not 6 or 8 also upregulated IEX-1. The IEX-1 mRNA levels were higher in RA-SFs than in OA-SFs, and were further upregulated in RA-SFs by the pro-inflammatory cytokines TNFα and IL-1β. The staining of surgical specimens showed that IEX-1 was present in the pannus from affected RA joints. Si-RNA-mediated IEX-1 knockdown upregulated the lipopolysaccharide (LPS-induced expression of TNFα and various chemokine mRNAs, indicating that IEX-1 downregulates TNFα and chemokines. Furthermore, apoptosis analysis showed that IEX-1 knockdown protected RA-SFs from apoptosis induced by TSA or by an anti-Fas mAb, indicating that IEX-1 is pro-apoptotic in RA-SFs. Collectively, our results showed that IEX-1 is induced by TNFα and IL-1β in RA-SFs, in which it suppresses TNFα and chemokine production and induces apoptosis; thus, IEX-1 negatively regulates RA-SF activation. Further investigation of IEX1's functions

Effect of Fibroblast Growth Factor 2 on Equine Synovial Fluid Chondroprogenitor Expansion and Chondrogenesis

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Marta Bianchessi

2016-01-01

Full Text Available Mesenchymal stem cells have been identified in the synovial fluid of several species. This study was conducted to characterize chondroprogenitor (CP cells in equine synovial fluid (SF and to determine the effect of fibroblast growth factor 2 (FGF-2 on SF-CP monolayer proliferation and subsequent chondrogenesis. We hypothesized that FGF-2 would stimulate SF-CP proliferation and postexpansion chondrogenesis. SF aspirates were collected from adult equine joints. Colony-forming unit (CFU assays were performed during primary cultures. At first passage, SF-cells were seeded at low density, with or without FGF-2. Following monolayer expansion and serial immunophenotyping, cells were transferred to chondrogenic pellet cultures. Pellets were analyzed for chondrogenic mRNA expression and cartilage matrix secretion. There was a mean of 59.2 CFU/mL of SF. FGF-2 increased the number of population doublings during two monolayer passages and halved the population doubling times. FGF-2 did not alter the immunophenotype of SF-CPs during monolayer expansion, nor did FGF-2 compromise chondrogenesis. Hypertrophic phenotypic markers were not expressed in control or FGF-2 groups. FGF-2 did prevent the development of a “fibroblastic” cell layer around pellet periphery. FGF-2 significantly accelerates in vitro SF-CP expansion, the major hurdle to clinical application of this cell population, without detrimentally affecting subsequent chondrogenic capacity.

TLR3 Ligand Poly(I:C Exerts Distinct Actions in Synovial Fibroblasts When Delivered by Extracellular Vesicles

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Mojca Frank-Bertoncelj

2018-01-01

Full Text Available Extracellular vesicles (EV can modulate the responses of cells to toll-like receptor (TLR ligation; conversely, TLR ligands such as double-stranded RNA (dsRNA can enhance the release of EV and influence of the composition and functions of EV cargos. Inflamed synovial joints in rheumatoid arthritis (RA are rich in EV and extracellular RNA; besides, RNA released from necrotic synovial fluid cells can activate the TLR3 signaling in synovial fibroblasts (SFs from patients with RA. Since EV occur prominently in synovial joints in RA and may contribute to the pathogenesis, we questioned whether EV can interact with dsRNA, a TLR3 ligand, and modify its actions in arthritis. We have used as model the effects on RA SFs, of EV released from monocyte U937 cells and peripheral blood mononuclear cells upon stimulation with Poly(I:C, a synthetic analog of dsRNA. We show that EV released from unstimulated cells and Poly(I:C-stimulated U937 cells [Poly(I:C EV] differ in size but bind similar amounts of Annexin V and express comparable levels of MAC-1, the receptor for dsRNA, on the vesicular membranes. Specifically, Poly(I:C EV contain or associate with Poly(I:C and at least partially protect Poly(I:C from RNAse III degradation. Poly(I:C EV shuttle Poly(I:C to SFs and reproduce the proinflammatory and antiviral gene responses of SFs to direct stimulation with Poly(I:C. Poly(I:C EV, however, halt the death receptor-induced apoptosis in SFs, thereby inverting the proapoptotic nature of Poly(I:C. These prosurvival effects sharply contrast with the high toxicity of cationic liposome-delivered Poly(I:C and may reflect the route of Poly(I:C delivery via EV or the fine-tuning of Poly(I:C actions by molecular cargo in EV. The demonstration that EV may safeguard extracellular dsRNA and allow dsRNA to exert antiapoptotic effects on SFs highlights the potential of EV to amplify the pathogenicity of dsRNA in arthritis beyond inflammation (by concurrently enhancing the

IL-15 expression on RA synovial fibroblasts promotes B cell survival.

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Marta Benito-Miguel

Full Text Available INTRODUCTION: The purpose of this study was to examine the role of RA Synovial Fibroblast (RASFib IL-15 expression on B cell survival. METHODS: Magnetically sorted peripheral blood memory B cells from 15 healthy subjects were cocultured with RASFib. RESULTS: RASFib constitutively expressed membrane IL-15. Survival of isolated B cells cultured for 6 days, below 5%, was extended in coculture with RASFib to 52+/-8% (p<0.001. IL-15 neutralizing agents but not isotype controls, reduced this rate to 31+/-6% (p<0.05. Interestingly, rhIL-15 had no effect on isolated B cells but significantly increased their survival in coculture with RASFib. In parallel, B cell IL-15R chains were upregulated in cocultures. BAFF and VCAM-1, that are expressed on RASFib, were tested as potential candidates involved in upregulating B cell IL-15R. Culture of B cells in the presence of rhBAFF or rhVCAM-1 resulted in significantly increased survival, together with upregulation of all three IL-15R chains; in parallel, rhIL-15 potentiated the anti-apoptotic effect of BAFF and VCAM-1. Both BAFF and VCAM-1 neutralizing agents downmodulated the effect of RASFib on B cell survival and IL-15R expression. In parallel, rhIL-15 had a lower effect on the survival of B cells cocultured with RASFib in the presence of BAFF or VCAM-1 neutralizing agents. Peripheral blood B cells from 15 early RA patients demonstrated an upregulated IL-15R and increased survival in cocultures. CONCLUSION: IL-15 expression on RASFib significantly contributes to the anti-apoptotic effect of RASFib on B cells. IL-15 action is facilitated by BAFF and VCAM-1 expressed on RASFib, through an upregulation of IL-15R chains.

Myostatin Promotes Interleukin-1β Expression in Rheumatoid Arthritis Synovial Fibroblasts through Inhibition of miR-21-5p

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Sung-Lin Hu

2017-12-01

Full Text Available Rheumatoid arthritis (RA is characterized by the infiltration of a number of pro-inflammatory cytokines into synovial fluid and patients with RA often develop joint destruction and deficits in muscle mass. The growth factor myostatin is a key regulator linking muscle mass and bone structure. We sought to determine whether myostatin regulates rheumatoid synovial fibroblast activity and inflammation in RA. We found that levels of myostatin and interleukin (IL-1β (a key pro-inflammatory cytokine in RA in synovial fluid from RA patients were overexpressed and positively correlated. In in vitro investigations, we found that myostatin dose-dependently regulated IL-1β expression through the ERK, JNK, and AP-1 signal-transduction pathways. Computational analysis confirmed that miR-21-5p directly targets the expression of the 3′ untranslated region (3′ UTR of IL-1β. Treatment of cells with myostatin inhibited miR-21-5p expression and miR-21-5p mimic prevented myostatin-induced enhancement of IL-1β expression, showing an inverse correlation between miR-21-5p and IL-1β expression during myostatin treatment. We also found significantly increased paw swelling in an animal model of collagen-induced arthritis (CIA, compared with controls; immunohistochemistry staining revealed substantially higher levels of myostatin and IL-1β expression in CIA tissue. Our evidence indicates that myostatin regulates IL-1β production. Thus, targeting myostatin may represent a potential therapeutic target for RA.

Tendon synovial cells secrete fibronectin in vivo and in vitro

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Banes, A.J.; Link, G.W.; Bevin, A.G.; Peterson, H.D.; Gillespie, Y.; Bynum, D.; Watts, S.; Dahners, L.

1988-01-01

The chemistry and cell biology of the tendon have been largely overlooked due to the emphasis on collagen, the principle structural component of the tendon. The tendon must not only transmit the force of muscle contraction to bone to effect movement, but it must also glide simultaneously over extratendonous tissues. Fibronectin is classified as a cell attachment molecule that induces cell spreading and adhesion to substratum. The external surface of intact avian flexor tendon stained positively with antibody to cellular fibronectin. However, if the surface synovial cells were first removed with collagenase, no positive reaction with antifibronectin antibody was detected. Analysis of immunologically stained frozen sections of tendon also revealed fibronectin at the tendon synovium, but little was associated with cells internal in tendon. The staining pattern with isolated, cultured synovial cells and fibroblasts from the tendon interior substantiated the histological observations. Analysis of polyacrylamide gel profiles of 35 S-methionine-labeled proteins synthesized by synovial cells and internal fibroblasts indicated that fibronectin was synthesized principally by synovial cells. Fibronectin at the tendon surface may play a role in cell attachment to prevent cell removal by the friction of gliding. Alternatively, fibronectin, with its binding sites for hyaluronic acid and collagen, may act as a complex for boundary lubrication

Acral synovial chondrosarcoma

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Wenger, D.E.; Sundaram, M.; Unni, K.K.; Janney, C.G.; Merkel, K.

2002-01-01

Acral chondrosarcoma is rare. Synovial chondrosarcoma is even rarer. Synovial chondrosarcoma arising without evidence of pre-existing or concurrent synovial chondromatosis is exceedingly rare. We present a case of acral synovial chondrosarcoma involving both sides of the metacarpophalangeal joint of the thumb in a 69-year-old man. Radiographically, the lesion mimicked gout. On MR imaging, the lobulated contours of the soft tissue mass suggested synovial chondromatosis. Histological examination revealed a chondrosarcoma, which on the basis of imaging findings we present as having arisen from the synovium. The tumor invaded a portion of the cartilage of the metacarpophalangeal joint and equally destroyed the bones of the distal metacarpal and base of the proximal phalanx of the thumb, while sparing the bony joint surfaces. (orig.)

Cellular interactions of synovial fluid γδ T cells in juvenile idiopathic arthritis.

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Bendersky, Anna; Marcu-Malina, Victoria; Berkun, Yackov; Gerstein, Maya; Nagar, Meital; Goldstein, Itamar; Padeh, Shai; Bank, Ilan

2012-05-01

The pathogenesis of juvenile idiopathic arthritis (JIA) is thought to involve multiple components of the cellular immune system, including subsets of γδ T cells. In this study, we conducted experiments to define the functional roles of one of the major synovial fluid (SF) T cell subsets, Vγ9(+)Vδ2(+) (Vγ9(+)) T cells, in JIA. We found that as opposed to CD4(+) T cells, equally high percentages (∼35%) of Vγ9(+) T cells in SF and peripheral blood (PB) produced TNF-α and IFN-γ. Furthermore, stimulation with isopentenyl pyrophosphate (IPP), a metabolite in the mevalonate pathway, which is a specific potent Ag for Vγ9Jγ1.2(+) T cells, similarly amplified cytokine secretion by SF and PB Vγ9(+) T cells. Significantly, the SF subset expressed higher levels of CD69 in situ, suggesting their recent activation. Furthermore, 24-h coculturing with SF-derived fibroblasts enhanced CD69 on the SF > PB Vγ9(+) T cells, a phenomenon strongly augmented by zoledronate, a farnesyl pyrophosphate synthase inhibitor that increases endogenous intracellular IPP. Importantly, although Vγ9(+) T cell proliferation in response to IPP was significantly lower in SF than PBMC cultures, it could be enhanced by depleting SF CD4(+)CD25(+)FOXP3(+) cells (regulatory T cells). Furthermore, coculture with the Vγ9(+) T cells in medium containing zoledronate or IPP strongly increased SF-derived fibroblasts' apoptosis. The findings that IPP-responsive proinflammatory synovial Vγ9(+) T cells for which proliferation is partly controlled by regulatory T cells can recognize and become activated by SF fibroblasts and then induce their apoptosis suggest their crucial role in the pathogenesis and control of synovial inflammation.

CD147 promotes IKK/IκB/NF-κB pathway to resist TNF-induced apoptosis in rheumatoid arthritis synovial fibroblasts.

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Zhai, Yue; Wu, Bo; Li, Jia; Yao, Xi-ying; Zhu, Ping; Chen, Zhi-nan

2016-01-01

TNF is highly expressed in synovial tissue of rheumatoid arthritis (RA) patients, where it induces proinflammatory cytokine secretion. However, in other cases, TNF will cause cell death. Considering the abnormal proliferation and activation of rheumatoid arthritis synovioblasts, the proper rate of synovioblast apoptosis could possibly relieve arthritis. However, the mechanism mediating TNF-induced synovioblast survival versus cell death in RA is not fully understood. Our objective was to study the role of CD147 in TNF downstream pathway preference in RA synovioblasts. We found that overexpressing TNF in synovial tissue did not increase the apoptotic level and, in vitro, TNF-induced mild synovioblast apoptosis and promoted IL-6 secretion. CD147, which was highly expressed in rheumatoid arthritis synovial fibroblasts (RASFs), increased the resistance of synovioblasts to apoptosis under TNF stimulation. Downregulating CD147 both increased the apoptotic rate and inhibited IκB kinase (IKK)/IκB/NF-κB pathway-dependent proinflammatory cytokine secretion. Further, we determined that it was the extracellular portion of CD147 and not the intracellular portion that was responsible for synovioblast apoptosis resistance. CD147 monoclonal antibody inhibited TNF-induced proinflammatory cytokine production but had no effect on apoptotic rates. Thus, our study indicates that CD147 is resistant to TNF-induced apoptosis by promoting IKK/IκB/NF-κB pathway, and the extracellular portion of CD147 is the functional region. CD147 inhibits TNF-stimulated RASF apoptosis. CD147 knockdown decreases IKK expression and inhibits NF-κB-related cytokine secretion. CD147's extracellular portion is responsible for apoptosis resistance. CD147 antibody inhibits TNF-related cytokine secretion without additional apoptosis.

Fibroblastic rheumatism

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Jyoti Ranjan Parida

2017-01-01

Full Text Available Fibroblastic rheumatism (FR is a rare dermoarthopathy reported from different parts of the world since 1980. Although the exact cause is unknown, few reports implicate infection may be a triggering event. Patients usually present with multiple skin nodules and polyarthropathy with progressive skin contractures. Laboratory parameters including acute phase reactants are usually normal. The confirmatory diagnosis is based on histopathologic study of skin nodules, which demonstrate fibroblastic proliferation, thickened collagen fibers, dermal fibrosis, and decreased number of elastic fibers. Immunoreactivity for b-catenin, smooth muscle actin, and the monoclonal antibody HHF35 show myofibroblastic differentiation. Treatments with oral prednisolone and other disease-modifying drugs such as methotrexate, infliximab, and interferon have been tried with variable success. In general, skin lesions respond more aptly than joint symptoms indicating that skin fibroblast is more amenable to treatment than synovial fibroblasts. Awareness regarding this orphan disease among clinicians and pathologists will help in more reporting of such cases and finding out optimal treatment regimen.

Chemical Hypoxia Brings to Light Altered Autocrine Sphingosine-1-Phosphate Signalling in Rheumatoid Arthritis Synovial Fibroblasts

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Chenqi Zhao

2015-01-01

Full Text Available Emerging evidence suggests a role for sphingosine-1-phosphate (S1P in various aspects of rheumatoid arthritis (RA pathogenesis. In this study we compared the effect of chemical hypoxia induced by cobalt chloride (CoCl2 on the expression of S1P metabolic enzymes and cytokine/chemokine secretion in normal fibroblast-like synoviocytes (FLS and RAFLS. RAFLS incubated with CoCl2, but not S1P, produced less IL-8 and MCP-1 than normal FLS. Furthermore, incubation with the S1P2 and S1P3 receptor antagonists, JTE-013 and CAY10444, reduced CoCl2-mediated chemokine production in normal FLS but not in RAFLS. RAFLS showed lower levels of intracellular S1P and enhanced mRNA expression of S1P phosphatase 1 (SGPP1 and S1P lyase (SPL, the enzymes that are involved in intracellular S1P degradation, when compared to normal FLS. Incubation with CoCl2 decreased SGPP1 mRNA and protein and SPL mRNA as well. Inhibition of SPL enhanced CoCl2-mediated cytokine/chemokine release and restored autocrine activation of S1P2 and S1P3 receptors in RAFLS. The results suggest that the sphingolipid pathway regulating the intracellular levels of S1P is dysregulated in RAFLS and has a significant impact on cell autocrine activation by S1P. Altered sphingolipid metabolism in FLS from patients with advanced RA raises the issue of synovial cell burnout due to chronic inflammation.

Th1-Induced CD106 Expression Mediates Leukocytes Adhesion on Synovial Fibroblasts from Juvenile Idiopathic Arthritis Patients.

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Maggi, Laura; Margheri, Francesca; Luciani, Cristina; Capone, Manuela; Rossi, Maria Caterina; Chillà, Anastasia; Santarlasci, Veronica; Mazzoni, Alessio; Cimaz, Rolando; Liotta, Francesco; Maggi, Enrico; Cosmi, Lorenzo; Del Rosso, Mario; Annunziato, Francesco

2016-01-01

This study tested the hypothesis that subsets of human T helper cells can orchestrate leukocyte adhesion to synovial fibroblasts (SFbs), thus regulating the retention of leukocytes in the joints of juvenile idiopathic arthritis (JIA) patients. Several cell types, such as monocytes/macrophages, granulocytes, T and B lymphocytes, SFbs and osteoclasts participate in joint tissue damage JIA. Among T cells, an enrichment of classic and non-classic Th1 subsets, has been found in JIA synovial fluid (SF), compared to peripheral blood (PB). Moreover, it has been shown that IL-12 in the SF of inflamed joints mediates the shift of Th17 lymphocytes towards the non-classic Th1 subset. Culture supernatants of Th17, classic and non-classic Th1 clones, have been tested for their ability to stimulate proliferation, and to induce expression of adhesion molecules on SFbs, obtained from healthy donors. Culture supernatants of both classic and non-classic Th1, but not of Th17, clones, were able to induce CD106 (VCAM-1) up-regulation on SFbs. This effect, mediated by tumor necrosis factor (TNF)-α, was crucial for the adhesion of circulating leukocytes on SFbs. Finally, we found that SFbs derived from SF of JIA patients expressed higher levels of CD106 than those from healthy donors, resembling the phenotype of SFbs activated in vitro with Th1-clones supernatants. On the basis of these findings, we conclude that classic and non-classic Th1 cells induce CD106 expression on SFbs through TNF-α, an effect that could play a role in leukocytes retention in inflamed joints.

CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis

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Karpus, Olga N.; Kiener, Hans P.; Niederreiter, Birgit; Yilmaz-Elis, A. Seda; van der Kaa, Jos; Ramaglia, Valeria; Arens, Ramon; Smolen, Josef S.; Botto, Marina; Tak, Paul P.; Verbeek, J. Sjef; Hamann, Jörg

2015-01-01

CD55, a glycosylphosphatidylinositol-anchored, complement-regulating protein (decay-accelerating factor), is expressed by fibroblast-like synoviocytes (FLS) with high local abundance in the intimal lining layer. We here explored the basis and consequences of this uncommon presence. Synovial tissue,

Synovial Chondrosarcoma in the Hand and Wrist: A Case Report

International Nuclear Information System (INIS)

An, Yeong Yi; Kim, Jee Young; Kang, Seok Jin; Kang, Yong Koo; Baik, Jun Hyun

2010-01-01

Synovial chondrosarcoma is extremely rare and arises de novo or from malignant transformation of synovial chondromatosis. It commonly involves large joints, such as the knee or hip. Here, we present an unusual case of synovial chondrosarcoma from synovial chondromatosis in the hand and wrist, clearly demonstrating the characteristic findings on plain radiograph and MR imaging

Synovial Chondrosarcoma in the Hand and Wrist: A Case Report

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An, Yeong Yi; Kim, Jee Young; Kang, Seok Jin; Kang, Yong Koo; Baik, Jun Hyun [Catholic University St. Vincent' s Hospital, Suwon (Korea, Republic of)

2010-01-15

Synovial chondrosarcoma is extremely rare and arises de novo or from malignant transformation of synovial chondromatosis. It commonly involves large joints, such as the knee or hip. Here, we present an unusual case of synovial chondrosarcoma from synovial chondromatosis in the hand and wrist, clearly demonstrating the characteristic findings on plain radiograph and MR imaging.

Synovial tissue hypoxia and inflammation in vivo.

LENUS (Irish Health Repository)

Ng, C T

2012-02-01

INTRODUCTION: Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine the relationship of partial oxygen pressure in the synovial tissue (tPO(2)) in patients with inflammatory arthritis with macroscopic\\/microscopic inflammation and local levels of proinflammatory mediators. METHODS: Patients with inflammatory arthritis underwent full clinical assessment and video arthroscopy to quantify macroscopic synovitis and measure synovial tPO(2) under direct visualisation. Cell specific markers (CD3 (T cells), CD68 (macrophages), Ki67 (cell proliferation) and terminal deoxynucleotidyl transferase dUTP nick end labelling (cell apoptosis)) were quantified by immunohistology. In vitro migration was assessed in primary and normal synoviocytes (synovial fibroblast cells (SFCs)) using a wound repair scratch assay. Levels of tumour necrosis factor alpha (TNFalpha), interleukin 1beta (IL1beta), interferon gamma (IFNgamma), IL6, macrophage inflammatory protein 3alpha (MIP3alpha) and IL8 were quantified, in matched serum and synovial fluid, by multiplex cytokine assay and ELISA. RESULTS: The tPO(2) was 22.5 (range 3.2-54.1) mm Hg and correlated inversely with macroscopic synovitis (r=-0.421, p=0.02), sublining CD3 cells (-0.611, p<0.01) and sublining CD68 cells (r=-0.615, p<0.001). No relationship with cell proliferation or apoptosis was found. Primary and normal SFCs exposed to 1% and 3% oxygen (reflecting the median tPO(2) in vivo) induced cell migration. This was coupled with significantly higher levels of synovial fluid tumour necrosis factor alpha (TNFalpha), IL1beta, IFNgamma and MIP3alpha in patients with tPO(2) <20 mm Hg (all p values <0.05). CONCLUSIONS: This is the first study to show a direct in vivo correlation between synovial tPO(2), inflammation and cell migration, thus it is proposed that hypoxia is a possible primary driver of inflammatory processes in the arthritic joint.

Synovial fluid analysis

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Joint fluid analysis; Joint fluid aspiration ... El-Gabalawy HS. Synovial fluid analysis, synovial biopsy, and synovial pathology. In: Firestein GS, Budd RC, Gabriel SE, McInnes IB, O'Dell JR, eds. Kelly's Textbook of ...

Synovial DKK1 expression is regulated by local glucocorticoid metabolism in inflammatory arthritis

OpenAIRE

Hardy, Rowan; Juarez, Maria; Naylor, Amy; Tu, Jinwen; Rabbitt, Elizabeth H; Filer, Andrew; Stewart, Paul M; Buckley, Christopher D; Raza, Karim; Cooper, Mark S

2012-01-01

Introduction: Inflammatory arthritis is associated with increased bone resorption and suppressed bone formation. The Wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. Local glucocorticoid production is also significantly increased during joint inflammation. Therefore, we investigated how locally derived glucocorticoids and inflammatory cytok...

Synovial Lipomatosis of the Glenohumeral Joint

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Shaul Beyth

2016-01-01

Full Text Available Synovial lipomatosis (also known as lipoma arborescens is a rare and benign lesion affecting synovium-lined cavities. It is characterized by hyperplasia of mature fat tissue in the subsynovial layer. Although the most commonly affected site is the knee joint, rarely additional locations such as tendon sheath and other joints are involved. We present a case of synovial lipomatosis of the glenohumeral joint in a 44-year-old man. The clinical data radiological studies and histopathologic results are described, as well as a review of the current literature.

The Synovial Lining and Synovial Fluid Properties after Joint Arthroplasty

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Michael Shang Kung

2015-05-01

Full Text Available The lubrication of the cartilaginous structures in human joints is provided by a fluid from a specialized layer of cells at the surface of a delicate tissue called the synovial lining. Little is known about the characteristics of the fluids produced after a joint arthroplasty procedure. A literature review was carried out to identify papers that characterized the synovial lining and the synovial fluids formed after total hip or knee arthroplasty. Five papers about synovial lining histology and six papers about the lubricating properties of the fluids were identified. The cells making up the re-formed synovial lining, as well as the lining of interface membranes, were similar to the typical Type A and B synoviocytes of normal joints. The synovial fluids around joint replacement devices were typically lower in viscosity than pre-arthroplasty fluids but the protein concentration and phospholipid concentrations tended to be comparable, suggesting that the lining tissue function was preserved after arthroplasty. The widespread, long-term success of joint arthroplasty suggests that the lubricant formed from implanted joint synovium is adequate for good clinical performance in the majority of joints. The role the fluid plays in component wear or failure is a topic for future study.

Synovial Sarcoma of the Buccal Mucosa: A Rare Case Report

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Kumar T. S. Mahesh

2013-01-01

Full Text Available Synovial sarcoma (SS is a rare malignant neoplasm that arises most commonly in joint capsules and articular tendons, but its relationship to the synovium is not always obvious. Synovial sarcoma is a malignant soft tissue tumor representing 5.6% to 10% of all soft tissue sarcomas. They are termed SS because of their histologic resemblance to the synovium, but they rarely involve a synovial structure and are thought to arise from pluripotential mesenchymal cells. The tumor usually occurs in close association with tendon sheaths, bursae, and joint capsules, primarily in the para-articular regions of the extremities, with approximately 9% occurring in the head and neck region. Synovial sarcoma has been reported rarely in the oral cavity. We report a very rare case of Synovial sarcoma of the buccal mucosa in a 24-year-old male patient.

Synovial sarcoma: a rare presentation of parapharyngeal mass.

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Shaariyah, Mohd Mokhtar; Mazita, Ami; Masaany, Mansor; Razif, Mohd Yunus; Isa, Mohamed Rose; Asma, Abdullah

2010-06-01

Synovial sarcoma is a rare soft tissue sarcoma of the head and neck region involving the parapharyngeal space. The diagnosis of synovial sarcoma can be very challenging to the pathologists. We present a rare case of parapharyngeal synovial sarcoma in a young female patient who had a two-month history of left cervical intumescent mass at level II. The fine needle aspiration cytology of the mass was proved inconclusive. Transcervical excision of the mass was performed and the first case of parapharyngeal sarcoma was identified in our center by fluorescence in situ hybridization (FISH) technique. Repeat imaging revealed residual tumor. The patient successfully underwent a second excision of the residual tumor and received adjuvant radiotherapy.

Cell-contact-dependent activation of CD4+ T cells by adhesion molecules on synovial fibroblasts.

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Mori, Masato; Hashimoto, Motomu; Matsuo, Takashi; Fujii, Takao; Furu, Moritoshi; Ito, Hiromu; Yoshitomi, Hiroyuki; Hirose, Jun; Ito, Yoshinaga; Akizuki, Shuji; Nakashima, Ran; Imura, Yoshitaka; Yukawa, Naoichiro; Yoshifuji, Hajime; Ohmura, Koichiro; Mimori, Tsuneyo

2017-05-01

To determine how cell-cell contact with synovial fibroblasts (SF) influence on the proliferation and cytokine production of CD4 +  T cells. Naïve CD4 +  T cells were cultured with SF from rheumatoid arthritis patients, stimulated by anti-CD3/28 antibody, and CD4 +  T cell proliferation and IFN-γ/IL-17 production were analyzed. To study the role of adhesion molecules, cell contact was blocked by transwell plate or anti-intracellular adhesion molecule-1 (ICAM-1)/vascular cell adhesion molecule-1(VCAM-1) antibody. To study the direct role of adhesion molecules for CD4 +  T cells, CD161 +  or CD161 - naïve CD4 +  T cells were stimulated on plastic plates coated by recombinant ICAM-1 or VCAM-1, and the source of IFN-γ/IL-17 were analyzed. SF enhanced naïve CD4 +  T cell proliferation and IFN-γ/IL-17 production in cell-contact and in part ICAM-1-/VCAM-1-dependent manner. Plate-coated ICAM-1 and VCAM-1 enhanced naïve CD4 +  T cell proliferation and IFN-γ production, while VCAM-1 efficiently promoting IL-17 production. CD161 +  naïve T cells upregulating LFA-1 and VLA-4 were the major source of IFN-γ/IL-17 upon interaction with ICAM-1/VCAM-1. CD4 +  T cells rapidly expand and secrete IFN-γ/IL-17 upon cell-contact with SF via adhesion molecules. Interfering with ICAM-1-/VCAM-1 may be beneficial for inhibiting RA synovitis.

Synovial tissue research

DEFF Research Database (Denmark)

Orr, Carl; Sousa, Elsa; Boyle, David L

2017-01-01

The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis. The study of synovial tissue has advanced considerably throughout the past few decades from arthroplasty and blind needle biopsy to the use of arthroscopic and ultrasonographic technologies that enable...... easier visualization and improve the reliability of synovial biopsies. Rapid progress has been made in using synovial tissue to study disease pathogenesis, to stratify patients, to discover biomarkers and novel targets, and to validate therapies, and this progress has been facilitated by increasingly...... diverse and sophisticated analytical and technological approaches. In this Review, we describe these approaches, and summarize how their use in synovial tissue research has improved our understanding of rheumatoid arthritis and identified candidate biomarkers that could be used in disease diagnosis...

Subchondral synovial cysts (intra-osseous ganglion)

International Nuclear Information System (INIS)

Graf, L.; Freyschmidt, J.

1988-01-01

Twelve cases of subchondral synovial cysts (intra-osseous ganglion) have been seen and their clinical features, radiological findings and differential diagnosis are described. The lesion is a benign cystic tumour-like mass in the subchondral portion of a synovial joint. Our findings in respect of age, sex and localisation are compared with those of other authors. The aetiology and pathogenesis of the lesion is not completely understood. There is an increased incidence in middle life and joints with high dynamic and static stress are favoured, particularly in the lower extremities. Chronic stress or microtrauma, causing damage to the involved joint, therefore appears to be a plausible explanation. (orig.) [de

Macrophages in synovial inflammation

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Aisling eKennedy

2011-10-01

Full Text Available AbstractSynovial macrophages are one of the resident cell types in synovial tissue and while they remain relatively quiescent in the healthy joint, they become activated in the inflamed joint and, along with infiltrating monocytes/macrophages, regulate secretion of pro-inflammatory cytokines and enzymes involved in driving the inflammatory response and joint destruction. Synovial macrophages are positioned throughout the sub-lining layer and lining layer at the cartilage-pannus junction and mediate articular destruction. Sub-lining macrophages are now also considered as the most reliable biomarker for disease severity and response to therapy in rheumatoid arthritis (RA. There is a growing understanding of the molecular drivers of inflammation and an appreciation that the resolution of inflammation is an active process rather than a passive return to homeostasis, and this has implications for our understanding of the role of macrophages in inflammation. Macrophage phenotype determines the cytokine secretion profile and tissue destruction capabilities of these cells. Whereas inflammatory synovial macrophages have not yet been classified into one phenotype or another it is widely known that TNFα and IL-l, characteristically released by M1 macrophages, are abundant in RA while IL-10 activity, characteristic of M2 macrophages, is somewhat diminished.Here we will briefly review our current understanding of macrophages and macrophage polarisation in RA as well as the elements implicated in controlling polarisation, such as cytokines and transcription factors like NFκB, IRFs and NR4A, and pro-resolving factors, such as LXA4 and other lipid mediators which may promote a non-inflammatory, pro-resolving phenotype and may represent a novel therapeutic paradigm.

Magnetic Resonance Imaging Comparison of Intra-Articular Cavernous Synovial Hemangioma and Cystic Synovial Hyperplasia of the Knee

International Nuclear Information System (INIS)

De Filippo, M.; Rovani, C.; Sudberry, J. J.; Rossi, F.; Pogliacomi, F.; Zompatori, M.

2006-01-01

Purpose: To identify and compare magnetic resonance imaging (MRI) characteristics, with and without intravenous contrast medium, of cavernous synovial hemangiomas and cystic synovial hyperplasia. Material and Methods: Four cases of cavernous synovial hemangioma and five of cystic synovial hyperplasia of the knee were studied retrospectively. The patients (5 F and 4 M; 15-25 years of age) all had long-standing knee pain. At clinical examination we observed elastic swelling and pain without significant joint effusion. The patients underwent conventional radiography and MRI without and following intravenous contrast medium before arthroscopic biopsy. Results: The radiographs were interpreted as negative in all patients. MRI examination without contrast medium revealed a similar multicystic appearance for both lesions. Following intravenous contrast agent administration, cavernous synovial hemangiomas demonstrated avid, rather homogenous enhancement, whereas cystic synovial hyperplasia demonstrated less intense, peripheral enhancement only. Arthroscopy with histological examination of the lesions confirmed the MRI diagnosis in every case. Conclusion: In our experience, cavernous synovial hemangioma and cystic synovial hyperplasia have a similar appearance on unenhanced MRI, but can be reliably differentiated on the basis of enhancement characteristics following intravenous contrast administration. Keywords: Cavernous synovial hemangioma; cystic synovial hyperplasia; knee; MRI

Retroviral gene transfer of an antisense construct against membrane type 1 matrix metalloproteinase reduces the invasiveness of rheumatoid arthritis synovial fibroblasts.

Science.gov (United States)

Rutkauskaite, Edita; Volkmer, Dagmar; Shigeyama, Yukio; Schedel, Jörg; Pap, Geza; Müller-Ladner, Ulf; Meinecke, Ingmar; Alexander, Dorothea; Gay, Renate E; Drynda, Susanne; Neumann, Wolfram; Michel, Beat A; Aicher, Wilhelm K; Gay, Steffen; Pap, Thomas

2005-07-01

Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed prominently in rheumatoid arthritis synovial fibroblasts (RASFs), but the specific contribution of MT1-MMP to fibroblast-mediated destruction of articular cartilage is incompletely understood. This study used gene transfer of an antisense expression construct to assess the effects of MT1-MMP inhibition on the invasiveness of RASFs. Retroviral gene transfer of a pLXIN vector-based antisense RNA expression construct (MT1-MMPalphaS) to MT1-MMP was used to stably transduce RASFs. Levels of MT1-MMP RNA and protein were determined by quantitative polymerase chain reaction, Western blotting, and immunocytochemistry in MT1-MMPalphaS-transduced RASFs as well as in control cells, with monitoring for 60 days. The effects of MT1-MMPalphaS on the invasiveness of RASFs were analyzed in the SCID mouse co-implantation model of RA. MT1-MMPalphaS-transduced RASFs produced high levels of antisense RNA that exceeded endogenous levels of MT1-MMP messenger RNA by 15-fold and resulted in a down-regulation of MT1-MMP at the protein level. Inhibition of MT1-MMP production was maintained for 60 days and significantly reduced the invasiveness of RASFs in the SCID mouse model. Whereas prominent invasion into cartilage by non-transduced and mock-transduced RASFs was observed (mean invasion scores 3.0 and 3.1, respectively), MT1-MMPalphaS-transduced cells showed only moderate invasiveness (mean invasion score 1.8; P < 0.05). The data demonstrate that an antisense RNA expression construct against MT1-MMP can be generated and expressed in RASFs for at least 60 days. Inhibition of MT1-MMP significantly reduces the cartilage degradation by RASFs.

Immunohistochemical Analysis of Inflammatory Rheumatoid Synovial Tissues Using Anti-Human Podoplanin Monoclonal Antibody Panel.

Science.gov (United States)

Suzuki, Tomoto; Takakubo, Yuya; Oki, Hiroharu; Liu, Xing; Honma, Ryusuke; Naganuma, Yasushi; Goodman, Stuart B; Kaneko, Mika K; Kato, Yukinari; Takagi, Michiaki

2018-02-01

Podoplanin (PDPN) is a transmembrane sialoglycoprotein, which is expressed in several normal tissues and malignant tumors. Although PDPN expression in rheumatoid arthritis (RA) has been reported, the role of PDPN in RA and other arthritic conditions has not been fully elucidated. In this study, we examined PDPN expression in inflammatory synovial tissues using an anti-human PDPN (hPDPN) monoclonal antibody (mAb) panel to select the most useful one for evaluation of synovitis. Synovial tissue samples were obtained from 11 RA patients and 9 osteoarthritis (OA) patients undergoing joint surgery. PDPN-positive cells were immunostained by a panel of PDPN mAbs (NZ-1, LpMab-3, LpMab-7, LpMab-10, LpMab-12, LpMab-13, and LpMab-17), followed by cell grading of inflammation and cell counting of PDPN-positivity by a quantitative analyzer. Immunohistochemistry showed that PDPN was markedly expressed in both macrophage-like type A and fibroblast-like type B lining cells of the hyperplastic synovial lining cell layer, and macrophages and fibroblasts in the stroma of RA. Among anti-PDPN mAbs, LpMab-12 showed the highest score. In inflammatory OA synovium, PDPN expression was also detectable. Although LpMab-12 also showed the highest score in OA, the difference was not statistically significant. The inflammatory synovitis score of RA was significantly higher than that of OA. PDPN was expressed in inflammatory lining cells and sublining stroma of RA and OA synovium. In the seven anti-hPDPN antibodies examined, LpMab-12 was the most stainable antibody for PDPN in RA synovitis. Thus, LpMab-12 for PDPN has a possible and promising specific biomarker for evaluating synovitis in RA and inflammatory OA.

Clinicopathological correlations of podoplanin (gp38 expression in rheumatoid synovium and its potential contribution to fibroblast platelet crosstalk.

Directory of Open Access Journals (Sweden)

Manuel J Del Rey

Full Text Available Synovial fibroblasts (SF undergo phenotypic changes in rheumatoid arthritis (RA that contribute to inflammatory joint destruction. This study was undertaken to evaluate the clinical and functional significance of ectopic podoplanin (gp38 expression by RA SF.Expression of gp38 and its CLEC2 receptor was analyzed by immunohistochemistry in synovial arthroscopic biopsies from RA patients and normal and osteoarthritic controls. Correlation between gp38 expression and RA clinicopathological variables was analyzed. In patients rebiopsied after anti-TNF-α therapy, changes in gp38 expression were determined. Platelet-SF coculture and gp38 silencing in SF were used to analyze the functional contribution of gp38 to SF migratory and invasive properties, and to SF platelet crosstalk.gp38 was abundantly but variably expressed in RA, and it was undetectable in normal synovial tissues. Among clinicopathologigal RA variables, significantly increased gp38 expression was only found in patients with lymphoid neogenesis (LN, and RF or ACPA autoantibodies. Cultured synovial but not dermal fibroblasts showed strong constitutive gp38 expression that was further induced by TNF-α. In RA patients, anti-TNF-α therapy significantly reduced synovial gp38 expression. In RA synovium, CLEC2 receptor expression was only observed in platelets. gp38 silencing in cultured SF did not modify their migratory and invasive properties but reduced the expression of IL-6 and IL-8 genes induced by SF-platelet interaction.In RA, synovial expression of gp38 is strongly associated to LN and it is reduced after anti-TNF-α therapy. Interaction between gp38 and CLEC2 platelet receptor is feasible in RA synovium in vivo and can specifically contribute to gene expression by SF.

Monophasic Synovial Sarcoma Presenting as Mitral Valve Obstruction

Science.gov (United States)

Chokesuwattanaskul, Warangkana; Terrell, Jason; Jenkins, Leigh Ann

2010-01-01

We report the case of a 26-year-old man who experienced progressive left-sided chest pain and 2 episodes of near-syncope. Studies revealed a 15-cm mass in the upper left lung, a 10-cm mass in the medial base of the left lung, and a 5-cm left atrial mass that involved the left lung, infiltrated the left pulmonary vein, and prolapsed into the mitral valve, causing intermittent obstruction. The patient underwent surgical excision of the left atrial tumor. Pathologic evaluation confirmed the diagnosis of monophasic synovial sarcoma. To our knowledge, this is only the 3rd report of left atrial invasion and resultant mitral valve obstruction from a synovial sarcoma that infiltrated the pulmonary vein. We believe that this is the 1st documented case of a metastatic left atrial synovial sarcoma in monophasic form. PMID:20844626

Monocarboxylate transporter 4, associated with the acidification of synovial fluid, is a novel therapeutic target for inflammatory arthritis.

Science.gov (United States)

Fujii, Wataru; Kawahito, Yutaka; Nagahara, Hidetake; Kukida, Yuji; Seno, Takahiro; Yamamoto, Aihiro; Kohno, Masataka; Oda, Ryo; Taniguchi, Daigo; Fujiwara, Hiroyoshi; Ejima, Akika; Kishida, Tsunao; Mazda, Osam; Ashihara, Eishi

2015-11-01

Synovial fluid pH is decreased in patients with rheumatoid arthritis (RA); however, the underlying mechanisms are unclear. We undertook this study to examine the mechanism by which synovial fluid pH is regulated and to explore the possibility of a therapeutic strategy by manipulating this mechanism. We determined the pH and lactate concentration in synovial fluid from 16 RA patients. Cultured synovial fibroblasts (SFs) from the inflamed joints of 9 RA patients (RASFs) were examined for the expression of ion transporters that regulate intracellular and extracellular pH. The ion transporter up-regulated in RASF lines was then suppressed in RASFs by small interfering RNA (siRNA), and the effect of transfection on viability and proliferation was investigated. Finally, we examined the therapeutic effect of electrotransfer of monocarboxylate transporter 4 (MCT4)-specific siRNA into the articular synovium of mice with collagen-induced arthritis (CIA). Synovial fluid pH correlated inversely with both the Disease Activity Score in 28 joints using the C-reactive protein level and the synovial fluid lactate levels. RASFs exhibited up-regulated transcription of MCT4 messenger RNA. MCT4 exported intracellular lactate into the extracellular space. RASFs had significantly higher MCT4 protein levels than did SFs from patients with osteoarthritis. Knockdown of MCT4 induced intrinsic apoptosis of RASFs, thereby inhibiting their proliferation. Moreover, electrotransfer of MCT4-specific siRNA into the articular synovium of mice with CIA significantly reduced the severity of arthritis. RA activity correlated with decreased synovial fluid pH. This may be due to increased MCT4 expression in RASFs. Silencing MCT4 induced apoptosis in RASFs and reduced the severity of CIA, suggesting that MCT4 is a potential therapeutic target for inflammatory arthritis. © 2015, American College of Rheumatology.

Synovial osteochondromatosis of the temporomandibular joint

International Nuclear Information System (INIS)

Nemnon, Jorge; Nemnon, Marcelo; Staffieri, Roberto; Villavicencio, C.; Marconi, G.; Masjoan, Diego

2004-01-01

Synovial osteochondromatosis (SO) is a meta plastic process by which synovial mesenchymal cells transform into chondroblasts and chondrocytes. This disease affects most frequently the knee, the hip, the elbow, and uncommonly the temporomandibular joint (TMJ). The authors present 2 cases of synovial osteochondromatosis of the TMJ. (author)

Krüppel-Like Factor 4 Is a Regulator of Proinflammatory Signaling in Fibroblast-Like Synoviocytes through Increased IL-6 Expression

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Xinjing Luo

2016-01-01

Full Text Available Human fibroblast-like synoviocytes play a vital role in joint synovial inflammation in rheumatoid arthritis (RA. Proinflammatory cytokines induce fibroblast-like synoviocyte activation and dysfunction. The inflammatory mediator Krüppel-like factor 4 is upregulated during inflammation and plays an important role in endothelial and macrophage activation during inflammation. However, the role of Krüppel-like factor 4 in fibroblast-like synoviocyte activation and RA inflammation remains to be defined. In this study, we identify the notion that Krüppel-like factor 4 is higher expressed in synovial tissues and fibroblast-like synoviocytes from RA patients than those from osteoarthritis patients. In vitro, the expression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes is induced by proinflammatory cytokine tumor necrosis factor-α. Overexpression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes robustly induced interleukin-6 production in the presence or absence of tumor necrosis factor-α. Conversely, knockdown of Krüppel-like factor 4 markedly attenuated interleukin-6 production in the presence or absence of tumor necrosis factor-α. Krüppel-like factor 4 not only can bind to and activate the interleukin-6 promoter, but also may interact directly with nuclear factor-kappa B. These results suggest that Krüppel-like factor 4 may act as a transcription factor mediating the activation of fibroblast-like synoviocytes in RA by inducing interleukin-6 expression in response to tumor necrosis factor-α.

Analysis of the cell infiltrate and expression of matrix metalloproteinases and granzyme B in paired synovial biopsy specimens from the cartilage-pannus junction in patients with RA

NARCIS (Netherlands)

Smeets, T. J.; Kraan, M. C.; Galjaard, S.; Youssef, P. P.; Smith, M. D.; Tak, P. P.

2001-01-01

Examination of synovial tissue (ST) obtained at surgery because of end stage destructive rheumatoid arthritis (RA) showed that macrophages and fibroblasts are the major cell types at the cartilage-pannus junction (CPJ). This study aimed at defining the cell infiltrate and mediators of joint

Synovial folds in equine articular process joints

DEFF Research Database (Denmark)

Thomsen, Line Nymann; Berg, Lise Charlotte; Markussen, Bo

2013-01-01

Cervical synovial folds have been suggested as a potential cause of neck pain in humans. Little is known about the extent and characteristics of cervical synovial folds in horses.......Cervical synovial folds have been suggested as a potential cause of neck pain in humans. Little is known about the extent and characteristics of cervical synovial folds in horses....

System-wide analysis reveals a complex network of tumor-fibroblast interactions involved in tumorigenicity.

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Megha Rajaram

Full Text Available Many fibroblast-secreted proteins promote tumorigenicity, and several factors secreted by cancer cells have in turn been proposed to induce these proteins. It is not clear whether there are single dominant pathways underlying these interactions or whether they involve multiple pathways acting in parallel. Here, we identified 42 fibroblast-secreted factors induced by breast cancer cells using comparative genomic analysis. To determine what fraction was active in promoting tumorigenicity, we chose five representative fibroblast-secreted factors for in vivo analysis. We found that the majority (three out of five played equally major roles in promoting tumorigenicity, and intriguingly, each one had distinct effects on the tumor microenvironment. Specifically, fibroblast-secreted amphiregulin promoted breast cancer cell survival, whereas the chemokine CCL7 stimulated tumor cell proliferation while CCL2 promoted innate immune cell infiltration and angiogenesis. The other two factors tested had minor (CCL8 or minimally (STC1 significant effects on the ability of fibroblasts to promote tumor growth. The importance of parallel interactions between fibroblasts and cancer cells was tested by simultaneously targeting fibroblast-secreted amphiregulin and the CCL7 receptor on cancer cells, and this was significantly more efficacious than blocking either pathway alone. We further explored the concept of parallel interactions by testing the extent to which induction of critical fibroblast-secreted proteins could be achieved by single, previously identified, factors produced by breast cancer cells. We found that although single factors could induce a subset of genes, even combinations of factors failed to induce the full repertoire of functionally important fibroblast-secreted proteins. Together, these results delineate a complex network of tumor-fibroblast interactions that act in parallel to promote tumorigenicity and suggest that effective anti

Synovial sarcoma of the abdominal wall

International Nuclear Information System (INIS)

Matushita, J.P.K.; Matushita, J.S.

1989-01-01

A case report of synovial sarcoma arising in the abdominal wall is presented. A brief review of the clinical and radiological features of synovial sarcoma is made. Pre-operative diagnosis of an abdominal wall synovial sarcoma is virtually impossible, but should be considered when a soft tissue swelling is found to show amorphous stippled calcification X-ray. (author) [pt

Synovial Lipoma of the Subtalar Joint.

Science.gov (United States)

Whitaker, Jeffrey M; Richards, Sarah; LeCastre, Michael J; Hooke, Thomas G

2017-07-01

Lipomas are benign adipose masses that are rarely associated with synovial membranes. In addition, there are only a few reports describing synovial lipomas in the foot. No reported occurrence of this lesion in the subtalar joint currently exists. This case report documents the presentation, clinical evaluation, advanced imaging, and surgical management of a 45-year-old man with a large synovial lipoma of the subtalar joint.

Primary renal synovial sarcoma

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Girish D. Bakhshi

2012-03-01

Full Text Available Primary Renal Sarcoma is rare tumor comprising only 1% of all renal tumours. Synovial sarcomas are generally deep-seated tumors arising in the proximity of large joints of adolescents and young adults and account for 5-10% of all soft tissue tumours. Primary synovial sarcoma of kidney is rare and has poor prognosis. It can only be diagnosed by immunohistochemistry. It should be considered as a differential in sarcomatoid and spindle cell tumours. We present a case of 33-year-old female, who underwent left sided radical nephrectomy for renal tumour. Histopathology and genetic analysis diagnosed it to be primary renal synovial sarcoma. Patient underwent radiation therapy and 2 years follow up is uneventful. A brief case report with review of literature is presented.

Angiography of histopathologic variants of synovial sarcoma

International Nuclear Information System (INIS)

Lois, J.F.; Fischer, H.J.; Mirra, J.M.; Gomes, A.S.; California Univ., Los Angeles

1986-01-01

Synovial sarcomas are rare soft tissue tumors which histopathologically can be divided into monophasic, biphasic and mixed variants. As part of a protocol for intra-arterial chemotherapy 12 patients with biopsy proven synovial sarcoma underwent angiography. The angiograms on these patients were reviewed to determine whether synovial sarcomas and their variants demonstrated a characteristic angiographic appearance. Synovial sarcomas appeared angiographically as soft tissue masses which showed a fine network of tumor vessels with an inhomogeneous capillary blush. Their degree of vascularity varied according to their histopathology. Monophasic synovial sarcomas demonstrated in general a higher degree of neovascularity than the biphasic form. This finding was also suggested by histopathologic analysis of the vessels in the tumor. Although angiography did not show a distinctive vascular pattern it may be useful to evaluate tumor size and vascularity. (orig.)

Synovial sarcoma: MR evaluation in 23 patients

International Nuclear Information System (INIS)

Galant, J.; Marti-Bonmati, L.; Lafuente, J.; Hernandez, L.; Soler, R.; Saez, F.

1997-01-01

The synovial sarcoma is one of the most common soft tissue sarcomas. MR is the technique of choice to determine to local extension of malignant soft tissue tumors. To assess the clinical and MR imaging parameters associated with synovial sarcomas that aid in establishing their diagnosis. We review the clinical findings and images of 23 histologically confirmed synovial sarcomas that were studied by MR. Synovial sarcomas usually develop in young adults as soft tissue tumors, preferentially in the deep tissues of an extremity in close proximity to a joint. They are characterized as having a lobulated contour and septa, frequently infiltrating neighboring tissues at some point, and are heterogeneous. The presence of hemorrhage, as well as infiltration of the fascia in subcutaneous tumors, suggests the diagnosis of synovial sarcoma. The development of perilesional edema is not uncommon. Although, logically, the clinical and radiological features of synovial sarcomas can overlap with those of other soft tissue tumors, the findings described here are fairly characteristic of these lesions: thus, when present, they should serve to orient the diagnostic process. (Author) 16 refs

Synovial chondromatosis of the knee

Energy Technology Data Exchange (ETDEWEB)

Haanraadts, E.J. [Dept. of Radiology, Onze Lieve Vrouwe Gasthuis, Amsterdam (Netherlands); Taconis, W.K. [Dept. of Radiology, Onze Lieve Vrouwe Gasthuis, Amsterdam (Netherlands); Huib, J.; Hout, W. van den [Dept. of Radiology, University Hospital, Utrecht (Netherlands); Feldberg, M.A.M. [Dept. of Radiology, University Hospital, Utrecht (Netherlands)

1992-02-01

A case of synovial chondromatosis with extensive modern cross-sectional imaging ``workup`` is presented. The case is of interest because it shows in plain films the natural development of the osteo-cartilaginous bodies in an 8-year period. Computed tomography and magnetic resonance imaging are only of relative value in the diagnosis of synovial chondromatosis. However, both modalities have a superior efficacy in differentiating synovial chondromatosis from other entities: the joint capsule can be seen, a quantitative definition of the density of the soft tissue mass and the loose bodies is possible, which can be a key feature of diagnosis. Secondary bone erosion can be differentiated from destruction. (orig.)

Liquid crystals in biotribology synovial joint treatment

CERN Document Server

Ermakov, Sergey; Eismont, Oleg; Nikolaev, Vladimir

2016-01-01

This book summarizes the theoretical and experimental studies confirming the concept of the liquid-crystalline nature of boundary lubrication in synovial joints. It is shown that cholesteric liquid crystals in the synovial liquid play a significant role in the mechanism of intra-articular friction reduction. The results of structural, rheological and tribological research of the creation of artificial synovial liquids - containing cholesteric liquid crystals in natural synovial liquids - are described. These liquid crystals reproduce the lubrication properties of natural synovia and provide a high chondroprotective efficiency. They were tested in osteoarthritis models and in clinical practice.

Synovial chondrosarcoma: Report of two cases and literature review

Energy Technology Data Exchange (ETDEWEB)

Zamora, E.E. [Department of Orthopaedic Surgery, Hospital Dr. R.A Calderon Guardia, Universidad De Costa Rica, P.O. Box 628-3000, Heredia (Costa Rica); Musculoskeletal Oncology Department, Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136 Bologna (Italy); Mansor, A. [Musculoskeletal Oncology Department, Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136 Bologna (Italy); Department of Orthopaedic Surgery, University of Malaya, Kuala Lumpur 59100 (Malaysia); Vanel, D. [Musculoskeletal Oncology Research Center, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna (Italy)], E-mail: dvanel@ior.it; Errani, C.; Mercuri, M. [Musculoskeletal Oncology Department, Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136 Bologna (Italy); Picci, P. [Musculoskeletal Oncology Research Center, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna (Italy); Alberghini, M. [Musculoskeletal Anatomical Pathology Department, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136 Bologna (Italy)

2009-10-15

Synovial chondrosarcoma is a rare soft tissue tumor that can arise from a previous synovial chondromatosis or as de novo tumor. The clinical and radiological findings of this malignancy are very similar to those of aggressive synovial chondromatosis. Confusion with other joint pathologies makes the diagnosis of synovial chondrosarcoma difficult in most of the cases. We present one recently diagnosed and treated case of synovial chondrosarcoma. The review of our hospital database revealed one more similar case. In both cases the malignancy arose from a pre-existing synovial chondromatosis. We also present a literature review emphasizing the clinical and histological findings of this rare entity.

Synovial inflammation in patients with different stages of knee osteoarthritis.

Science.gov (United States)

Ene, Răzvan; Sinescu, Ruxandra Diana; Ene, Patricia; Cîrstoiu, Monica Mihaela; Cîrstoiu, Florin Cătălin

2015-01-01

The synovium is an intra-articular mesenchymal tissue and essential for the normal joint function. It is involved in many pathological characteristic processes and sometimes specific for this distinctive tissue. In this study, we refer to synovial proliferative disorders according to the stage of osteoarthritis (OA) disease. Forty-three patients with knee OA were treated in the Department of Orthopedics and Traumatology, Emergency University Hospital of Bucharest, Romania, in the last two years. In all cases, we used at least five criteria for the knee OA: knee pain, knee joint tenderness, no palpable warmth over the knee, stiffness, erythrocyte sedimentation rate and C-reactive protein levels. In all the cases the synovial tissue was selected by the orthopedic surgeon. X-ray examination was taken in every case of the affected joint. Patients who were considered to have early OA underwent arthroscopic synovial biopsy of the symptomatic joint. Synovial tissue samples from patients with late OA were obtained at the time of knee joint arthroplasty. Microscopic examination in early osteoarthritis revealed for more than half of patients with synovial biopsy through arthroscopic technique having synovitis lesions with mononuclear infiltrates, diffuse fibrosis, thickening of the lining layer, macrophages appearance and neoformation vessels also. The synovitis seen in advanced OA knees tends to be diffuse and is not mandatory localized to areas of chondral defects, although an association has been reported between chondral defects and associated synovitis in the knee medial tibio-femoral compartment. The overexpression of mediators of inflammation and the increased mononuclear cell infiltration were seen in early OA, compared with late OA.

Synovial and tenosynovial lipoma arborescens of the ankle in an adult: a case report

International Nuclear Information System (INIS)

Babar, S.A.; Mitchell, A.W.; Sandison, A.

2008-01-01

Lipoma arborescens is a rare benign fat-containing synovial proliferative lesion that is typically known to affect the knee joint in adults. We present the first case of lipoma arborescens of the ankle joint in an adult patient with involvement of the intra-articluar synovium as well as the synovial sheath of the tendons around the ankle. The MRI features of this lesion in the adult ankle are described. (orig.)

Intraneural synovial sarcoma of the median nerve

Directory of Open Access Journals (Sweden)

Rahul Kasukurthi

2010-06-01

Full Text Available Synovial sarcomas are soft-tissue malignancies with a poor prognosis and propensity for distant metastases. Although originally believed to arise from the synovium, these tumors have been found to occur anywhere in the body. We report a rare case of synovial sarcoma arising from the median nerve. To our knowledge, this is the twelfth reported case of intraneural synovial sarcoma, and only the fourth arising from the median nerve. Because the diagnosis may not be apparent until after pathological examination of the surgical speci­men, synovial sarcoma should be kept in mind when dealing with what may seem like a benign nerve tumor.

Acute serum amyloid A induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/SCID mouse chimera model.

LENUS (Irish Health Repository)

Connolly, Mary

2010-06-01

Serum amyloid A (A-SAA), an acute-phase protein with cytokine-like properties, is expressed at sites of inflammation. This study investigated the effects of A-SAA on chemokine-regulated migration and angiogenesis using rheumatoid arthritis (RA) cells and whole-tissue explants in vitro, ex vivo, and in vivo. A-SAA levels were measured by real-time PCR and ELISA. IL-8 and MCP-1 expression was examined in RA synovial fibroblasts, human microvascular endothelial cells, and RA synovial explants by ELISA. Neutrophil transendothelial cell migration, cell adhesion, invasion, and migration were examined using transwell leukocyte\\/monocyte migration assays, invasion assays, and adhesion assays with or without anti-MCP-1\\/anti-IL-8. NF-kappaB was examined using a specific inhibitor and Western blotting. An RA synovial\\/SCID mouse chimera model was used to examine the effects of A-SAA on cell migration, proliferation, and angiogenesis in vivo. High expression of A-SAA was demonstrated in RA patients (p < 0.05). A-SAA induced chemokine expression in a time- and dose-dependent manner (p < 0.05). Blockade with anti-scavenger receptor class B member 1 and lipoxin A4 (A-SAA receptors) significantly reduced chemokine expression in RA synovial tissue explants (p < 0.05). A-SAA induced cell invasion, neutrophil-transendothelial cell migration, monocyte migration, and adhesion (all p < 0.05), effects that were blocked by anti-IL-8 or anti-MCP-1. A-SAA-induced chemokine expression was mediated through NF-kappaB in RA explants (p < 0.05). Finally, in the RA synovial\\/SCID mouse chimera model, we demonstrated for the first time in vivo that A-SAA directly induces monocyte migration from the murine circulation into RA synovial grafts, synovial cell proliferation, and angiogenesis (p < 0.05). A-SAA promotes cell migrational mechanisms and angiogenesis critical to RA pathogenesis.

Case report 460: Synovial chondrosarcoma of left knee

International Nuclear Information System (INIS)

Manivel, J.C.; Dehner, L.P.; Thompson, R.

1988-01-01

The case is presented of a 50-year-old man who presented with a mass around the left knee which radiologically was calcified heavily and eroded bone. A final diagnosis over a period of time of synovial chondrosarcoma was established. A description in depth of the types of synovial chondromatosis and the possible etiology of synovial chondrosarcoma was included in the manuscript. The diagnostic (radiological and pathological) features of the entity were described and the rarity of synovial chondrosarcoma was emphasized. (orig.)

[Diagnosis: synovial fluid analysis].

Science.gov (United States)

Gallo Vallejo, Francisco Javier; Giner Ruiz, Vicente

2014-01-01

Synovial fluid analysis in rheumatological diseases allows a more accurate diagnosis in some entities, mainly infectious and microcrystalline arthritis. Examination of synovial fluid in patients with osteoarthritis is useful if a differential diagnosis will be performed with other processes and to distinguish between inflammatory and non-inflammatory forms. Joint aspiration is a diagnostic and sometimes therapeutic procedure that is available to primary care physicians. Copyright © 2014 Elsevier España, S.L. All rights reserved.

Metabolomic Elucidation of the Effects of Curcumin on Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

OpenAIRE

Ahn, Joong Kyong; Kim, Sooah; Hwang, Jiwon; Kim, Jungyeon; Lee, You Sun; Koh, Eun-Mi; Kim, Kyoung Heon; Cha, Hoon-Suk

2015-01-01

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by synovial inflammation and joint disability. Curcumin is known to be effective in ameliorating joint inflammation in RA. To obtain new insights into the effect of curcumin on primary fibroblast-like synoviocytes (FLS, N = 3), which are key effector cells in RA, we employed gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS)-based metabolomics. Metabolomic profiling of tumor necrosis factor (TNF)-α...

Metacarpophalangeal joint synovial pad fibrotic proliferation in 63 horses

International Nuclear Information System (INIS)

Dabareiner, R.M.; White, N.A.; Sullins, K.E.

1996-01-01

Medical records, radiographs, and sonograms of 63 horses with metacarpophalangeal joint synovial pad proliferation were examined retrospectively. AR horses had lameness, joint effusion, or both signs associated with one or both metacarpophalangeal joints. Bony remodeling and concavity of the distodorsal aspect of the third metacarpal bone (Mc3) just proximal to the metacarpal condyles was identified by radiography in 71 joints (93%); 24 joints (32%) had radiographic evidence of a chip fracture located at the proximal dorsal aspect of the proximal phalanx. Fifty-four joints (71%) were examined by ultrasound. The mean +- SD sagittal thickness of the synovial pad was 11.3 +- 2.8 mm. Seventy-nine percent of the horses had single joint involvement with equal distribution between the right and left forelimbs. Sixty-eight joints in 55 horses were treated by arthroscopic surgery. Sixty joints (88%) had debridement of chondral or osteochondral fragmentation from the dorsal surface of Mc3 beneath the synovial pad and 30 joints (44%) had a bone chip fracture removed from the medial or lateral proximal dorsal eminence of the proximal phalanx. Complete or partial excision of both medial and lateral synovial pads was completed in 42 joints. Only the medial synovial pad was excised or trimmed in 21 joints, and 5 joints had only the lateral pad removed. Eight joints in eight horses were treated by stall rest, administration of intra-articular medication and systemic nonsteroidal anti-inflammatory drugs. Follow-up information was obtained for 50 horses treated surgically and for eight horses treated medically. Forty-three (86%) that had surgery returned to racing; 34 (68%) raced at an equivalent or better level than before surgery. Three (38%) of the medically treated horses returned to racing; only one horse raced better than the preinjury level. Horses that returned to racing at a similar or equal level of performance were significantly younger in age than horses returning at a

Synovial deposition of wild-type transthyretin-derived amyloid in knee joint osteoarthritis patients.

Science.gov (United States)

Takanashi, Tetsuo; Matsuda, Masayuki; Yazaki, Masahide; Yamazaki, Hideshi; Nawata, Masashi; Katagiri, Yoshiki; Ikeda, Shu-Ichi

2013-09-01

To investigate histological features of deposited amyloid in the synovial tissue and its clinical significance in knee joint osteoarthritis (OA) patients. We prospectively enrolled 232 consecutive patients who underwent arthroplasty or total replacement of the knee joint for treatment of OA. Congo red staining and immunohistochemistry were performed in the synovial tissue obtained at surgery. When transthyretin (TTR)-derived amyloid was positive, we analyzed all 4 exons of the TTR gene using the direct DNA sequencing method in order to detect mutations. We analyzed 322 specimens in this study. Twenty-six specimens (8.1%) obtained from 21 patients (5 men and 16 women; mean, 79.0 ± 4.6 years) showed deposition of amyloid, which was positively stained with the anti-TTR antibody. Eighteen patients showed inhomogeneous accumulations of amyloid in the loose connective tissue under the synovial epithelia sometimes with nodule formation, while in the remaining three, small vessels in the adipose tissue were involved. Medical records of these patients revealed nothing remarkable in the clinical course, laboratory data or macroscopic intraarticular findings at surgery. No mutations were detectable in the TTR gene analysis. Wild-type TTR-derived amyloid may affect the synovial tissue as a result of long-term mechanical stress or as a part of senile systemic amyloidosis in approximately 8% of knee joint OA patients. No obvious clinical significance was found in synovial deposition of amyloid.

Cyclophilin A secreted from fibroblast-like synoviocytes is involved in the induction of CD147 expression in macrophages of mice with collagen-induced arthritis

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Nishioku Tsuyoshi

2012-11-01

Full Text Available Abstract Background Cyclophilin A (CypA, a member of the immunophilin family, is a ubiquitously distributed intracellular protein. Recent studies have shown that CypA is secreted by cells in response to inflammatory stimuli. Elevated levels of extracellular CypA and its receptor, CD147 have been detected in the synovium of patients with RA. However, the precise process of interaction between CypA and CD147 in the development of RA remains unclear. This study aimed to investigate CypA secretion from fibroblast-like synoviocytes (FLS isolated from mice with collagen-induced arthritis (CIA and CypA-induced CD147 expression in mouse macrophages. Findings CIA was induced by immunization with type II collagen in mice. The expression and localization of CypA and CD147 was investigated by immunoblotting and immunostaining. Both CypA and CD147 were highly expressed in the joints of CIA mice. CD147 was expressed in the infiltrated macrophages in the synovium of CIA mice. In vitro, spontaneous CypA secretion from FLS was detected and this secretion was increased by stimulation with lipopolysaccharide. CypA markedly increased CD147 levels in macrophages. Conclusions These findings suggest that an interaction in the synovial joints between extracellular CypA and CD147 expressed by macrophages may be involved in the mechanisms underlying the development of arthritis.

Synovial cysts: clinical and neuroradiological aspects

International Nuclear Information System (INIS)

Artico, M.; Cervoni, L.; Carloia, S.; Stevanato, G.; Mastantuono, M.; Nucci, F.

1997-01-01

Lumbar and intraneural synovial cysts are uncommon lesions. although their incidence has increased since the introduction of MRI. The authors describe the results of a study comprising 23 patients with synovial cyst (5 lumbar, 19 intraneural). Neuroradiological investigations included CT scan and MRI; however, it was not always possible to diagnose the nature of the lesion. In 18 cases the lesion was removed totally including its capsule; in the other 5 cases it was removed subtotally. Seven of the 23 patients presented a total remission of symptoms/signs, 11 improved and 5 remained unchanged. The importance of treating synovial cysts as radically as possible is discussed together with their most significant clinical and neuroradiological aspects. (author)

Arthroscopic Treatment of a Case with Concomitant Subacromial and Subdeltoid Synovial Chondromatosis and Labrum Tear

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Nevres Hurriyet Aydogan

2013-01-01

Full Text Available Synovial chondromatosis is a disease that seldomly seen in shoulder joint and is related to benign synovial proliferation and synchronous chondral tissue formation within the joint cavity. Patients suffer from progressive restriction of range of motion and shoulder pain. Extra-articular involvement is an extremely rare condition. Degenerative osteoarthritis, joint subluxation, and bursitis are common complications in untreated patients. Open or arthroscopic surgery is suitable while there is no consensus related to superiority of different approaches. We presented an arthroscopic treatment of a male patient, 48 years old with labrum tear and synovial chondromatosis localized in subacromial and subdeltoid region. Advantages of arthroscopic surgery in the presence of intra- and extra-articular combined pathologies are also discussed.

Gross and histopathological findings in synovial membranes of pigs with experimentally induced Mycoplasma hyosynoviae arthritis

DEFF Research Database (Denmark)

Hagedorn-Olsen, T.; Basse, A.; Jensen, Tim Kåre

1999-01-01

or contact exposure with M. hyosynoviae induced arthritis in 13- to 17-week-old pigs. The acute to subacute arthritis was characterized by increased amounts of serohaemorrhagic, serofibrinous or mahogany coloured synovial fluid combined with edema and hyperaemia, followed by yellow to brownish discoloration...... and moderate villous proliferation of the synovial membrane. In the chronic phase moderate fibrosis was seen, but no periarticular or articular cartilage involvement. The acute to subacute histopathological characteristics were edema, hyperaemia, variable hyperplasia of synovial lining cells, increased density...... of subsynovial cell populations, diffuse and perivascular infiltration with lymphocytes, plasma cells and macrophage-like cells, fibrinous material, mild to moderate villous hypertrophy and mild to moderate fibrosis in chronic cases. The morphogenetic changes during the course of the infection may be described...

Hyaluronate synthesis by synovial villi in organ culture

International Nuclear Information System (INIS)

Myers, S.L.; Christine, T.A.

1983-01-01

Individual canine synovial villi were used to establish short-term synovial organ cultures. These villi incorporated 3 H-glucosamine into highly-polymerized 3 H-hyaluronic acid ( 3 H-HA), which was the only 3 H-glycosaminoglycan identified in the culture medium. Some 3 H-HA, and larger amounts of other 3 H-glycosaminoglycans, were recovered from cultured tissues. Culture medium 3 H-HA content was proportional to the surface area of cultured villi. Organ cultures of nonvillous synovium were compared with villi; nonvillous cultures synthesized less 3 H-HA per mm2 of their synovial intimal surface than villi. These cultures complement cell culture techniques for in vitro studies of synovial lining cell function

Involvement of 15-lipoxygenase in the inflammatory arthritis.

Science.gov (United States)

Wu, Ming-Yueh; Lin, Tzu-Hung; Chiu, Yung-Cheng; Liou, Houng-Chi; Yang, Rong-Sen; Fu, Wen-Mei

2012-07-01

15-Lipoxygenase (15-LOX) is involved in many pathological processes. The aim of this study is to examine the role of 15-LOX in the matrix metalloproteinase (MMP) expression and inflammatory arthritis. It was found that treatment of 15-LOX downstream product of 15-(S)-HETE (15-S-hydroxyeicosatetraenoic acid) increased the mRNA and protein levels of MMP-2 in rheumatoid arthritis synovial fibroblast (RASF) derived from rheumatoid arthritis patients. The enhancement effect of 15-(S)-HETE was antagonized by the addition of LY294002 (PI3K inhibitor) and PDTC (NF-κB inhibitor). Treatment of 15-(S)-HETE increased the phosphorylation of AKT, nuclear translocation of p65 and the breakdown of IκBα. TNF-α and IL-1β are the key cytokines involved in arthritis and also increase the activity of MMP-2 in RASF, which was antagonized by pretreatment with 15-LOX inhibitor PD146176 or knockdown of 15-LOX. It was also found that these two cytokines increased the expression of 15-LOX in RASF. Treatment of glucocorticoid but not NSAIDs inhibited 15-(S)-HETE-induced expression of MMP-2. In comparison with wild-type mice, adjuvant-induced arthritis and MMP-2 expression in synovial membrane were markedly inhibited in 15-LOX knockout (KO) mice. These results indicate that 15-LOX plays an important role in the disease progression of arthritis and may be involved in the inflammatory action induced by TNF-α and IL-1β. 15-LOX is thus a good target for developing drugs in the treatment of inflammatory arthritis. Copyright © 2012 Wiley Periodicals, Inc.

Synovial chondromatosis of the shoulder: imaging findings

International Nuclear Information System (INIS)

Terazaki, Carlos Renato Ticianelli; Trippia, Carlos Henrique; Caboclo, Maria Fernanda Sales Ferreira; Medaglia, Carla Regina Miranda

2014-01-01

Synovial chondromatosis is a benign condition characterized by synovial proliferation and metaplasia, with development of cartilaginous or osteocartilaginous nodules within a joint, bursa or tendon sheath. In the shoulder, synovial osteochondromatosis may occur within the glenohumeral joint and its recesses (including the tendon sheath of the biceps long head), and in the subacromial-deltoid bursa. Such condition can be identified either by radiography, ultrasonography or magnetic resonance imaging, showing typical features according to each method. Radiography commonly shows ring-shaped calcified cartilages and periarticular soft tissues swelling with erosion of joint margins. Ultrasonography demonstrates hypoechogenic cartilaginous nodules with progressive increase in echogenicity as they become calcified, with development of posterior acoustic shadow in case of ossification. Besides identifying cartilaginous nodules, magnetic resonance imaging can also demonstrate the degree of synovial proliferation. The present study is aimed at describing the imaging findings of this entity in the shoulder. (author)

Synovial chondromatosis of the shoulder: imaging findings

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Carlos Renato Ticianelli Terazaki

2014-02-01

Full Text Available Synovial chondromatosis is a benign condition characterized by synovial proliferation and metaplasia, with development of cartilaginous or osteocartilaginous nodules within a joint, bursa or tendon sheath. In the shoulder, synovial osteochondromatosis may occur within the glenohumeral joint and its recesses (including the tendon sheath of the biceps long head, and in the subacromial-deltoid bursa. Such condition can be identified either by radiography, ultrasonography or magnetic resonance imaging, showing typical features according to each method. Radiography commonly shows ring-shaped calcified cartilages and periarticular soft tissues swelling with erosion of joint margins. Ultrasonography demonstrates hypoechogenic cartilaginous nodules with progressive increase in echogenicity as they become calcified, with development of posterior acoustic shadow in case of ossification. Besides identifying cartilaginous nodules, magnetic resonance imaging can also demonstrate the degree of synovial proliferation. The present study is aimed at describing the imaging findings of this entity in the shoulder.

Synovial Fluid Analysis

Science.gov (United States)

... Plasma Free Metanephrines Platelet Count Platelet Function Tests Pleural Fluid Analysis PML-RARA Porphyrin Tests Potassium Prealbumin ... is being tested? Synovial fluid is a thick liquid that acts as a lubricant for the body's ...

A new inhibitor of synovial phospholipase A2 from fermentations of Penicillium sp. 62-92.

Science.gov (United States)

Witter, L; Anke, T; Sterner, O

1998-01-01

Penidiamide, a new tripetide containing dehydrotryptamine, glycine and anthranilic acid linked together by two amide bonds, and oxindole were isolated from submerged cultures of Penicillium sp. 62-92. Both compounds preferentially inhibited human synovial phospholipase A2, penidiamide with an IC50 of 30 microM and oxindole of 380 microM. With the exception of U 937 cells (leukemia, human), no cytotoxic activities were detected against HL-60- (leukemia, human), HeLa S3- (epitheloid carcinoma, human), BHK 21- (kidney fibroblasts, hamster), and L1210-cells (leukemia, mouse). No antimicrobial activity was detected for oxindole, and only weak antibacterial activity for penidiamide. The structure of penidiamide was elucidated by spectroscopic methods.

Multimodality management of primary diaphragmatic synovial sarcoma: First report

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Preyas J Vaidya

2016-01-01

Full Text Available Synovial cell sarcoma is an extremely rare tumor of mesenchymal origin. It commonly affects the soft tissues of the extremities but could possibly origin from the head and neck, heart, lung, pleura, mediastinum, esophagus, abdominal wall and the mesentery, and retroperitoneum. Primary synovial sarcoma of pleura, mediastinum, and lung have been reported. Primary synovial sarcoma of the diaphragm has not been reported to the best of our knowledge. We report a case of primary synovial cell sarcoma of the diaphragm presenting as a recurrent pleural effusion and pain in the left hypochondrium managed with multimodality approach.

Quantitative assessment of the synovial membrane in the rheumatoid wrist: an easily obtained MRI score reflects the synovial volume

DEFF Research Database (Denmark)

Østergaard, Mikkel; Hansen, M; Stoltenberg, M

1996-01-01

Determination of the synovial membrane volume in the rheumatoid arthritis (RA) wrist by gadolinium-DTPA-enhanced MRI is introduced. Moreover, dynamic imaging and an MRI score of synovial hypertrophy, based on gradings in six regions, are evaluated as substitutes of the time-consuming volume...

Magnetic particle translation as a surrogate measure for synovial fluid mechanics.

Science.gov (United States)

Shah, Yash Y; Maldonado-Camargo, Lorena; Patel, Neal S; Biedrzycki, Adam H; Yarmola, Elena G; Dobson, Jon; Rinaldi, Carlos; Allen, Kyle D

2017-07-26

The mechanics of synovial fluid vary with disease progression, but are difficult to quantify quickly in a clinical setting due to small sample volumes. In this study, a novel technique to measure synovial fluid mechanics using magnetic nanoparticles is introduced. Briefly, microspheres embedded with superparamagnetic iron oxide nanoparticles, termed magnetic particles, are distributed through a 100μL synovial fluid sample. Then, a permanent magnet inside a protective sheath is inserted into the synovial fluid sample. Magnetic particles translate toward the permanent magnet and the percentage of magnetic particles collected by the magnet in a given time can be related to synovial fluid viscosity. To validate this relationship, magnetic particle translation was demonstrated in three phases. First, magnetic particle translation was assessed in glycerol solutions with known viscosities, demonstrating that as fluid viscosity increased, magnetic particle translation decreased. Next, the relationship between magnetic particle translation and synovial fluid viscosity was assessed using bovine synovial fluid that was progressively degenerated via ultrasonication. Here, particle collection in a given amount of time increased as fluid degenerated, demonstrating that the relationship between particle collection and fluid mechanics holds in non-Newtonian synovial fluid. Finally, magnetic particle translation was used to assess differences between healthy and OA affected joints in equine synovial fluid. Here, particle collection in a given time was higher in OA joints relative to healthy horses (pfluid mechanics in limited volumes of synovial fluid sample. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular insights into the differences in anti-inflammatory activities of green tea catechins on IL-1β signaling in rheumatoid arthritis synovial fibroblasts.

Science.gov (United States)

Fechtner, Sabrina; Singh, Anil; Chourasia, Mukesh; Ahmed, Salahuddin

2017-08-15

In this study, we found that catechins found in green tea (EGCG, EGC, and EC) differentially interfere with the IL-1β signaling pathway which regulates the expression of pro-inflammatory mediators (IL-6 and IL-8) and Cox-2 in primary human rheumatoid arthritis synovial fibroblasts (RASFs). EGCG and EGC inhibited IL-6, IL-8, and MMP-2 production and selectively inhibited Cox-2 expression. EC did not exhibit any inhibitory effects. When we looked at the expression of key signaling proteins in the IL-1β signaling pathway, we found all the tested catechins could inhibit TAK-1 activity. Therefore, the consumption of green tea offers an overall anti-inflammatory effect. Molecular docking analysis confirms that EGCG, EGC, and EC all occupy the active site of the TAK1 kinase domain. However, EGCG occupies the majority of the TAK1 active site. In addition to TAK1 inhibition, EGCG can also inhibit P38 and nuclear NF-κB expression whereas EC and EGC were not effective inhibitors. Our findings suggest one of the main health benefits associated with the consumption of green tea are due to the activity of EGCG and EGC which are both present at higher amounts. Although EGCG is the most effective catechin at inhibiting downstream inflammatory signaling, its effectiveness could be hindered by the presence of EC. Therefore, varying EC content in green tea may reduce the anti-inflammatory effects of other potential catechins in green tea. Copyright © 2017. Published by Elsevier Inc.

Synovial sarcoma

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Sucari S.C. Vlok

2014-12-01

Full Text Available Synovial sarcoma is a malignant, predominantly juxta-articular, soft-tissue tumour representing approximately 10% of all soft-tissue sarcomas. Frequently initially incorrectly diagnosed as a benign lesion, it should be considered as a diagnosis when a young adult patient presents with a calcified juxta-articular soft-tissue mass of insidious onset.

MR imaging of abnormal synovial processes

International Nuclear Information System (INIS)

Quinn, S.F.; Sanchez, R.; Murray, W.T.; Silbiger, M.L.; Ogden, J.; Cochran, C.

1987-01-01

MR imaging can directly image abnormal synovium. The authors reviewed over 50 cases with abnormal synovial processes. The abnormalities include Baker cysts, semimembranous bursitis, chronic shoulder bursitis, peroneal tendon ganglion cyst, periarticular abscesses, thickened synovium from rheumatoid and septic arthritis, and synovial hypertrophy secondary to Legg-Calve-Perthes disease. MR imaging has proved invaluable in identifying abnormal synovium, defining the extent and, to a limited degree, characterizing its makeup

Bilateral generalised synovial chondromatosis of the knee: Bone scintigraphic demonstration with radiologic correlation

International Nuclear Information System (INIS)

Elri, Tarik; Cabuk, Mehmet; Salihoglu, Yavuz Sami; Erdemir, Rabiye Uslu; Serifoglu, Ismail

2016-01-01

A 67-year-old woman with a history of bilateral progressive knee pain and swelling was referred for 99m Tc-methyl diphosphonate bone scintigraphy. Flow and blood pool images showed bilateral heterogeneous increased uptake and delayed phase revealed mass-looking lobulated heterogeneous increased activity in both of knees extending distal part of the femoral shaft, but no other pathologic uptake was found in rest of the body. A diagnosis of synovial chondromatosis was made when correlated with X-ray and computed tomography.(CT) images. This is a rare presentation of generalized synovial chondromatosis involving both knees which demonstrated on bone scintigraphy with X-ray and CT correlation

The Histone Deacetylase Inhibitors MS-275 and SAHA Suppress the p38 Mitogen-Activated Protein Kinase Signaling Pathway and Chemotaxis in Rheumatoid Arthritic Synovial Fibroblastic E11 Cells

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Hai-Shu Lin

2013-11-01

Full Text Available MS-275 (entinostat and SAHA (vorinostat, two histone deacetylase (HDAC inhibitors currently in oncological trials, have displayed potent anti-rheumatic activities in rodent models of rheumatoid arthritis (RA. To further elucidate their anti-inflammatory mechanisms, the impact of MS-275 and SAHA on the p38 mitogen-activated protein kinase (MAPK signaling pathway and chemotaxis was assessed in human rheumatoid arthritic synovial fibroblastic E11 cells. MS-275 and SAHA significantly suppressed the expression of p38α  MAPK, but induced the expression of MAPK phosphatase-1 (MKP-1, an endogenous suppressor of p38α  in E11 cells. At the same time, the association between p38α and MKP-1 was up-regulated and consequently, the activation (phosphorylation of p38α  was inhibited. Moreover, MS-275 and SAHA suppressed granulocyte chemotactic protein-2 (GCP-2, monocyte chemotactic protein-2 (MCP-2 and macrophage migration inhibitory factor (MIF in E11 cells in a concentration-dependent manner. Subsequently, E11-driven migration of THP-1 and U937 monocytes was inhibited. In summary, suppression of the p38 MAPK signaling pathway and chemotaxis appear to be important anti-rheumatic mechanisms of action of these HDAC inhibitors.

Involvement of the mitochondrial compartment in human NCL fibroblasts

International Nuclear Information System (INIS)

Pezzini, Francesco; Gismondi, Floriana; Tessa, Alessandra; Tonin, Paola; Carrozzo, Rosalba; Mole, Sara E.; Santorelli, Filippo M.; Simonati, Alessandro

2011-01-01

Highlights: ► Mitochondrial reticulum fragmentation occurs in human CLN1 and CLN6 fibroblasts. ► Likewise mitochondrial shift-to periphery and decreased mitochondrial density are seen. ► Enhanced caspase-mediated apoptosis occurs following STS treatment in CLN1 fibroblasts. -- Abstract: Neuronal ceroid lipofuscinosis (NCL) are a group of progressive neurodegenerative disorders of childhood, characterized by the endo-lysosomal storage of autofluorescent material. Impaired mitochondrial function is often associated with neurodegeneration, possibly related to the apoptotic cascade. In this study we investigated the possible effects of lysosomal accumulation on the mitochondrial compartment in the fibroblasts of two NCL forms, CLN1 and CLN6. Fragmented mitochondrial reticulum was observed in all cells by using the intravital fluorescent marker Mitotracker, mainly in the perinuclear region. This was also associated with intense signal from the lysosomal markers Lysotracker and LAMP2. Likewise, mitochondria appeared to be reduced in number and shifted to the cell periphery by electron microscopy; moreover the mitochondrial markers VDCA and COX IV were reduced following quantitative Western blot analysis. Whilst there was no evidence of increased cell death under basal condition, we observed a significant increase in apoptotic nuclei following Staurosporine treatment in CLN1 cells only. In conclusion, the mitochondrial compartment is affected in NCL fibroblasts invitro, and CLN1 cells seem to be more vulnerable to the negative effects of stressed mitochondrial membrane than CLN6 cells.

Receptor protein tyrosine phosphatase alpha enhances rheumatoid synovial fibroblast signaling and promotes arthritis in mice

NARCIS (Netherlands)

Stanford, Stephanie M; Svensson, Mattias N D; Sacchetti, Cristiano; Pilo, Caila A; Wu, Dennis J; Kiosses, William B; Hellvard, Annelie; Bergum, Brith; Aleman Muench, German R; Elly, Christian; Liu, Yun-Cai; den Hertog, Jeroen; Elson, Ari; Sap, Jan; Mydel, Piotr; Boyle, David L; Corr, Maripat; Firestein, Gary S; Bottini, Nunzio

2016-01-01

OBJECTIVE: During rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) critically promote disease pathogenesis by aggressively invading the joint extracellular matrix. The focal adhesion kinase (FAK) signaling pathway is emerging as a contributor to RA FLS anomalous behavior. The receptor

Thymoquinone inhibits TNF-α-induced inflammation and cell adhesion in rheumatoid arthritis synovial fibroblasts by ASK1 regulation

Energy Technology Data Exchange (ETDEWEB)

Umar, Sadiq; Hedaya, Omar; Singh, Anil K.; Ahmed, Salahuddin, E-mail: salah.ahmed@wsu.edu

2015-09-15

Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine produced by monocytes/macrophage that plays a pathological role in rheumatoid arthritis (RA). In this study, we investigate the effect of thymoquinone (TQ), a phytochemical found in Nigella sativa, in regulating TNF-α-induced RA synovial fibroblast (RA-FLS) activation. Treatment with TQ (1–5 μM) had no marked effect on the viability of human RA-FLS. Pre-treatment of TQ inhibited TNF-α-induced interleukin-6 (IL-6) and IL-8 production and ICAM-1, VCAM-1, and cadherin-11 (Cad-11) expression in RA-FLS (p < 0.01). Evaluation of the signaling events showed that TQ inhibited TNF-α-induced phospho-p38 and phospho-JNK expression, but had no inhibitory effect on NF-κB pathway, in RA-FLS (p < 0.05; n = 4). Interestingly, we observed that selective down-regulation of TNF-α-induced phospho-p38 and phospho-JNK activation by TQ is elicited through inhibition of apoptosis-regulated signaling kinase 1 (ASK1). Furthermore, TNF-α selectively induced phosphorylation of ASK1 at Thr845 residue in RA-FLS, which was inhibited by TQ pretreatment in a dose dependent manner (p < 0.01). Pre-treatment of RA-FLS with ASK1 inhibitor (TC ASK10), blocked TNF-α induced expression of ICAM-1, VCAM-1, and Cad-11. Our results suggest that TNF-α-induced ASK1-p38/JNK pathway is an important mediator of cytokine synthesis and enhanced expression of adhesion molecule in RA-FLS and TQ, by selectively inhibiting this pathway, may have a potential therapeutic value in regulating tissue destruction observed in RA. - Highlights: • Evolving evidence suggests that ASK1 plays a central role in rheumatic arthritis (RA). • TNF-α activates ASK1, which regulate downstream signaling through JNK/p38 activation in RA-FLS. • ASK1 may be used as a potential therapeutic target in RA. • Thymoquinone was able to selectively inhibit TNF-α-induced phosphorylation of ASK1 in RA-FLS. • Thymoquinone might serve as a potential small

Imaging appearances of synovial plicae syndrome of the knee

OpenAIRE

Osama Abdalla Mabrouk Kheiralla

2016-01-01

Synovial plicae are synovial folds that may be found as intraarticular structures within the knee joint. They are remnants of incomplete resorption of mesenchymal tissue during fetal development. Synovial plicae, if present, are supposed to be non-pathological and asymptomatic, however if they are exposed to special events like direct trauma or repeated activities, they may be inflamed and become fibrosed and rigid and irritates the synovium of the underlying femoral condyle resul...

A double patella-like condition secondary to synovial osteochondromatosis

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Kajikawa Yoshiteru

2012-09-01

Full Text Available Abstract To our knowledge, this is the first case of synovial osteochondromatosis in a patient presenting with a double patella-like condition. The true duplication of the patella, which is called double patella, is extremely rare. In our case, the operative and histopathological findings showed that the double patella-like condition was secondarily induced by synovial osteochondromatosis. Synovial osteochondromatosis should be considered as a differential diagnosis for congenital double patella.

Role of reactive oxygen species in rheumatoid arthritis synovial T lymphocytes

NARCIS (Netherlands)

Remans, Philip Herman Jozef

2006-01-01

In rheumatoid arthritis, an inflammatory infiltrate accumulates and persists in the synovial membrane. Synovial T cells display a number of particular characteristics. While displaying markers of recent activation, synovial T lymphocytes respond poorly to mitogenic stimuli and their cytokine

IL-34 Upregulated Th17 Production through Increased IL-6 Expression by Rheumatoid Fibroblast-Like Synoviocytes

OpenAIRE

Wang, Bing; Ma, Zijian; Wang, Miaomiao; Sun, Xiaotong; Tang, Yawei; Li, Ming; Zhang, Yan; Li, Fang; Li, Xia

2017-01-01

Rheumatoid arthritis (RA) is a chronic autoimmune disease which is characterized by synovial inflammation and cartilage damage for which causes articular dysfunction. Activation of fibroblast-like synoviocytes (FLS) is a critical step that promotes disease progression. In this study, we aimed to explore the effect of interleukin-34 (IL-34) on RA FLS as a proinflammatory factor and IL-34-stimulated FLS on the production of Th17. We found that serum IL-34 levels were increased compared to those...

Synovial sarcoma mechanisms

DEFF Research Database (Denmark)

Svejstrup, Jesper Q

2013-01-01

Human synovial sarcoma is caused by a chromosome translocation, which fuses DNA encoding SSX to that encoding the SS18 protein. Kadoch and Crabtree now show that the resulting cellular transformation stems from disruption of the normal architecture and function of the human SWI/SNF (BAF) complex....

Possible involvement of loss of imprinting in immortalization of human fibroblasts.

Science.gov (United States)

Okamura, Kotaro; Ohno, Maki; Tsutsui, Takeki

2011-04-01

Disruption of the normal pattern of parental origin-specific gene expression is referred to as loss of imprinting (LOI), which is common in various cancers. To investigate a possible role of LOI in the early stage of human cell transformation, we studied LOI in 18 human fibroblast cell lines immortalized spontaneously, by viral oncogenes, by chemical or physical carcinogens, or by infection with a retrovirus vector encoding the human telomerase catalytic subunit, hTERT cDNA. LOI was observed in all the 18 immortal cell lines. The gene most commonly exhibiting LOI was NDN which displayed LOI in 15 of the 18 cell lines (83%). The other genes exhibiting LOI at high frequencies were PEG3 (50%), MAGE-L2 (61%) and ZNF 127 (50%). Expression of NDN that was lost in the immortal cell lines was restored by treatment with 5-aza-2'-deoxycytidine. The ratio of histone H3 lysine 9 methylation to histone H3 lysine 4 methylation of the chromatin containing the NDN promoter in the immortal WI-38VA13 cells was greater than that in the parental cells, suggesting chromatin structure-mediated regulation of NDN expression. We previously demonstrated that inactivation of the p16INK4a/pRb pathway is necessary for immortalization of human cells. Human fibroblasts in the pre-crisis phase and cells with an extended lifespan that eventually senesce, both of which have the normal p16INK4a/pRb pathway, did not show LOI at any imprinted gene examined. Although it is not clear if LOI plays a causal role in immortalization of human cells or is merely coincidental, these findings indicate a possible involvement of LOI in immortalization of human cells or a common mechanism involved in both processes.

Synovial explant inflammatory mediator production corresponds to rheumatoid arthritis imaging hallmarks

DEFF Research Database (Denmark)

Andersen, Martin; Boesen, Mikael; Ellegaard, Karen

2014-01-01

was to compare site-specific release of inflammatory mediators and evaluate the corresponding anatomical sites by examining colour Doppler ultrasound (CDUS) and MRI scans. METHODS: RA patients were evaluated on the basis of CDUS and 3-T MRI scans and subsequently underwent synovectomy using a needle arthroscopic.......02, approximate Spearman's ρ = 0.63). IL-8 associations with imaging outcome measures did not reach statistical significance. CONCLUSIONS: The association between imaging activity and synovial inflammatory mediators underscores the high sensitivity of CDUS and MRI in the evaluation of RA disease activity....... The associations found in our present study have different implications for synovial mediator releases and corresponding imaging signs. For example, MCP-1 and IL-6 were associated with both general inflammation and bone destruction, in contrast to MIP-1β, which was involved solely in general synovitis. The lack...

Intraosseus and extraosseus juxtaarticular calcification: Osteopoikilosis with synovial osteochondromatosis - an association

Directory of Open Access Journals (Sweden)

Parangama Chatterjee

2009-03-01

Full Text Available

Osteopoikilosis presents as round or ovoid sclerotic lesions with an appearance like enostosis on pathology. Synovial osteochondromatosis occurs due to cartilaginous metaplasia with synovial villous proliferation with calcified nodules in proximity to joints. A case of osteopoikilosis associated with synovial osteochondromatosis is described. Intraosseus and juxta osseus sclerotic bone lesions were identified on radiographs and computed tomography in a patient with knee pain. The association of osteopoikilosis with synovial osteochondromatosis is rare and to our knowledge has received little attention in the literature.

Extensor and flexor digit synovial sheath, sac and synovial capsule in the distal part of the limbs in buffalos and camels and its relation of surgical interference

Directory of Open Access Journals (Sweden)

S. AL-sadi

2010-01-01

Full Text Available Sixty one samples of the distal parts of limbs were obtained from different ages of buffalo and camels of both sex to study the synovial structures to determine the suitable sites for injection of surgical interference. The result showed that extensor digit synovial sheath was extend between middle or distal part of metacarpal (metatarsal to the extensor processes and this formed with synovial capsule dorsal pouches which serve in surgical interference. The flexor digit synovial sheath extended to palmar (planter between distal extremity of metacarpal (metatarsal to the middle of second phalanx in buffalo while in camel it extended to the proximal extremity of second phalanx, that sheath was formed with suspensory ligament and sessamoid bone palmar or planter pouches which were serve the surgical interference. Fourth synovial bursa observed situated dorsally between the extensor digit laterals tendon and capsule of fetlock joint, forms site of injection during surgical interference, while the other two synovial bursa were located to palmer (planter between deep flexor tendon and distal sessamoid bone in buffalo while in camel these bursa were located between deep flexor tendon and cartilage of the second phalanx, these bursa were served for surgical interference. The synovial capsule which serve the surgical interference through digit cushion these were shown extended from the claw capsule. The result show that surgical interference was form six pouches in buffalo and eight pouches in camel, which formed by synovial structures and the tissue associated with them.

A case of synovial sarcoma in the submandibular region

International Nuclear Information System (INIS)

Sakata, Chie; Kinoshita, Toshibumi; Kaminou, Toshio; Adachi, Akira; Kinoshita, Fumiko; Ogawa, Toshihide

2005-01-01

Synovial sarcomas are a less common cervical tumor in young patients. We report a 23-year-old man with synovial sarcoma in the submandibular region. T2-weighted MR images demonstrated a mixed-intensity tumor attached to the submandibular gland. T1-weighted MR images revealed a focal area with mildly increased signal intensity, indicating intratumoral hemorrhage. MR images were also useful for visualization of tumor extension. Synovial sarcoma should be considered in the differential diagnosis of well-defined in homogeneous tumors adjacent to the submandibular gland in young adults. (author)

Primary Cystic Pleuropulmonary Synovial Sarcoma Presenting as Recurrent Pneumothorax

Directory of Open Access Journals (Sweden)

Eric D. Johnson

2017-07-01

Full Text Available Primary pleuropulmonary synovial sarcomas are quite rare, representing 0.1–0.5% of all pulmonary malignancies. We report an entirely cystic monophasic synovial sarcoma in a 25-year-old male who presented with recurrent pneumothorax and no evidence of a mass lesion on imaging. The purpose of this case report is to increase awareness of neoplasms clinically presenting as a pneumothorax with no imagining evidence of a mass-forming lesion and emphasize the significance of fluorescent in situ hybridization testing in nontypical synovial sarcoma cases.

Synovial Sarcoma-A Rare Tumor of the Larynx

Directory of Open Access Journals (Sweden)

Ghodrat Mohammadi

2016-05-01

Full Text Available Introduction: Malignant mesenchymal tumors of the larynx are rare. One type of malignant mesenchymal tumor is synovial sarcoma with unknown histogenesis, which occurs predominantly in the lower extremities of young adults. The head and neck region is a relatively rare location. There are few cases of malignant mesenchymal tumors with laryngeal localization in literature.  Case Report: In this report, a new case in a 23-year-old man, which was referred with increasing hoarseness for eight months, and dysphagia, odynophagia, and dyspnea since nearly one year ago, is reported. Indirect laryngoscopy revealed a laryngeal submucosal mass. The patient was operated and the histopathological diagnosis of synovial sarcoma was confirmed by IHC (Immunohistochemisry.  Conclusion:  Synovial sarcoma occurs predominantly in the lower extremities of young adults. Because very few cases of laryngeal synovial sarcoma are reported, every new case will bring some new information about diagnosis and therapy. It is of utmost importance to get to know new aspects and therapeutical modalities of this rare tumor.

Complete human serum maintains viability and chondrogenic potential of human synovial stem cells: suitable conditions for transplantation.

Science.gov (United States)

Mizuno, Mitsuru; Katano, Hisako; Otabe, Koji; Komori, Keiichiro; Kohno, Yuji; Fujii, Shizuka; Ozeki, Nobutake; Horie, Masafumi; Tsuji, Kunikazu; Koga, Hideyuki; Muneta, Takeshi; Sekiya, Ichiro

2017-06-13

In our clinical practice, we perform transplantations of autologous synovial mesenchymal stem cells (MSCs) for cartilage and meniscus regenerative medicine. One of the most important issues to ensuring clinical efficacy involves the transport of synovial MSCs from the processing facility to the clinic. Complete human serum (100% human serum) is an attractive candidate material in which to suspend synovial MSCs for their preservation during transport. The purpose of this study was to investigate whether complete human serum maintained MSC viability and chondrogenic potential and to examine the optimal temperature conditions for the preservation of human synovial MSCs. Human synovium was harvested from the knees of 14 donors with osteoarthritis during total knee arthroplasty. Passage 2 synovial MSCs were suspended at 2 million cells/100 μL in Ringer's solution or complete human serum at 4, 13, and 37 °C for 48 h. These cells were analyzed for live cell rates, cell surface marker expression, metabolic activity, proliferation, and adipogenic, calcification, and chondrogenic differentiation potentials before and after preservation. After preservation, synovial MSCs maintained higher live cell rates in human serum than in Ringer's solution at 4 and 13 °C. Synovial MSCs preserved in human serum at 4 and 13 °C also maintained high ratios of propidium iodide - and annexin V - cells. MSC surface marker expression was not altered in cells preserved at 4 and 13 °C. The metabolic activities of cells preserved in human serum at 4 and 13 °C was maintained, while significantly reduced in other conditions. Replated MSCs retained their proliferation ability when preserved in human serum at 4 and 13 °C. Adipogenesis and calcification potential could be observed in cells preserved in each condition, whereas chondrogenic potential was retained only in cells preserved in human serum at 4 and 13 °C. The viability and chondrogenic potential of synovial MSCs were

Toward understanding the role of cartilage particulates in synovial inflammation.

Science.gov (United States)

Silverstein, A M; Stefani, R M; Sobczak, E; Tong, E L; Attur, M G; Shah, R P; Bulinski, J C; Ateshian, G A; Hung, C T

2017-08-01

Arthroscopy with lavage and synovectomy can remove tissue debris from the joint space and the synovial lining to provide pain relief to patients with osteoarthritis (OA). Here, we developed an in vitro model to study the interaction of cartilage wear particles with fibroblast-like synoviocytes (FLS) to better understand the interplay of cartilage particulates with cytokines on cells of the synovium. In this study sub-10 μm cartilage particles or 1 μm latex particles were co-cultured with FLS ±10 ng/mL interleukin-1α (IL-1α) or tumor necrosis factor-α (TNF-α). Samples were analyzed for DNA, glycosaminoglycan (GAG), and collagen, and media samples were analyzed for media GAG, nitric oxide (NO) and prostaglandin-E2 (PGE2). The nature of the physical interaction between the particles and FLS was determined by microscopy. Both latex and cartilage particles could be phagocytosed by FLS. Cartilage particles were internalized and attached to the surface of both dense monolayers and individual cells. Co-culture of FLS with cartilage particulates resulted in a significant increase in cell sheet DNA and collagen content as well as NO and PGE2 synthesis compared to control and latex treated groups. The proliferative response of FLS to cartilage wear particles resulted in an overall increase in extracellular matrix (ECM) content, analogous to the thickening of the synovial lining observed in OA patients. Understanding how cartilage particles interface with the synovium may provide insight into how this interaction contributes to OA progression and may guide the role of lavage and synovectomy for degenerative disease. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Synovial haemangioma presenting as monarticular arthritis of the knee.

OpenAIRE

Hawley, W L; Ansell, B M

1981-01-01

Two children with haemangioma of the synovial membrane presenting as swelling of a knee joint are described; in one patient this was associated with epiphyseal overgrowth. This condition should be considered if blood synovial fluid is obtained and clotting studies are normal.

Recurrent Mycobacterium marinum tenosynovitis of the wrist mimicking extraarticular synovial chondromatosis on MR images

Energy Technology Data Exchange (ETDEWEB)

Lee, Edward Y.; Rubin, David A. [Department of Radiology, Mallinckrodt Institute of Radiology, St. Louis, MO (United States); Brown, David M. [The Orthopedic Center of St. Louis, St. Louis, MO (United States)

2004-07-01

Tenosynovitis caused by atypical mycobacterial infections may produce rice bodies within affected tendon sheaths. We report a case of recurrent M. marinum infection involving the flexor tendons within the carpal tunnel in which the rice bodies were mistaken for synovial chondromatosis on MR images. (orig.)

Recurrent Mycobacterium marinum tenosynovitis of the wrist mimicking extraarticular synovial chondromatosis on MR images

International Nuclear Information System (INIS)

Lee, Edward Y.; Rubin, David A.; Brown, David M.

2004-01-01

Tenosynovitis caused by atypical mycobacterial infections may produce rice bodies within affected tendon sheaths. We report a case of recurrent M. marinum infection involving the flexor tendons within the carpal tunnel in which the rice bodies were mistaken for synovial chondromatosis on MR images. (orig.)

Synovial osteochondromatosis of the temporomandibular joint; Osteocondromatosis sinovial en la articulacion temporomandibular

Energy Technology Data Exchange (ETDEWEB)

Nemnon, Jorge; Nemnon, Marcelo; Staffieri, Roberto; Villavicencio, C; Marconi, G; Masjoan, Diego [Fundacion Villavicencio, Rosario (Argentina). Diagnostico Medico

2004-07-01

Synovial osteochondromatosis (SO) is a meta plastic process by which synovial mesenchymal cells transform into chondroblasts and chondrocytes. This disease affects most frequently the knee, the hip, the elbow, and uncommonly the temporomandibular joint (TMJ). The authors present 2 cases of synovial osteochondromatosis of the TMJ. (author)

Prednisolone phosphate-containing TRX-20 liposomes inhibit cytokine and chemokine production in human fibroblast-like synovial cells: a novel approach to rheumatoid arthritis therapy.

Science.gov (United States)

Harigai, Takashi; Hagiwara, Hitomi; Ogawa, Yumi; Ishizuka, Takanobu; Kaneda, Shinichi; Kimura, Junji

2007-01-01

To evaluate the potential of using prednisolone phosphate (PSLP)-containing 3,5-dipentadecyloxybenzamidine hydrochloride (TRX-20) liposomes to treat rheumatoid arthritis (RA), we examined their ability to bind human fibroblast-like synovial (HFLS) cells and their effects in these cells. To test for binding, Lissamine rhodamine B-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (rhodamine)-labelled PSLP-containing TRX-20 liposomes were added to HFLS cells, and the fluorescence intensity of the rhodamine bound to the cells was evaluated. Rhodamine-labelled PSLP-containing liposomes without TRX-20 were used as a negative control. To evaluate the uptake of liposomes by the HFLS cells, we used TRX-20 liposomes containing 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) and p-xylene-bis-pyridinium bromide (DPX), and observed the cells by fluorescence microscopy. The effects of the PSLP in TRX-20 liposomes on HFLS cells were assessed by the inhibition of the production of two inflammatory cytokines (interleukin 6 and granulocyte macrophage colony-stimulating factor) and one inflammatory chemokine (interleukin 8). The interaction of the PSLP-containing TRX-20 liposomes with HFLS cells was approximately 40 times greater than that of PSLP-containing liposomes without TRX-20. PSLP-containing TRX-20 liposomes bound to HFLS cells primarily via chondroitin sulfate. TRX-20 liposomes taken up by the cell were localized to acidic compartments. Furthermore, the PSLP-containing TRX-20 liposomes inhibited the production of the inflammatory cytokines and the chemokine more effectively than did the PSLP-containing liposomes without TRX-20. These results indicate that PSLP-containing TRX-20 liposomes show promise as a novel drug delivery system that could enhance the clinical use of glucocorticoids for treating RA.

Poly(ADP-ribose) polymerase inhibition reduces tumor necrosis factor-induced inflammatory response in rheumatoid synovial fibroblasts

NARCIS (Netherlands)

García, S.; Bodaño, A.; Pablos, J. L.; Gómez-Reino, J. J.; Conde, C.

2008-01-01

To investigate the effect of poly(ADP-ribose) polymerase (PARP) inhibition on the production of inflammatory mediators and proliferation in tumour necrosis factor (TNF)-stimulated fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Cultured FLS from patients with RA were

Synovial chondromatosis of the elbow in a child

Directory of Open Access Journals (Sweden)

Rishi Narasimhan

2011-01-01

Full Text Available Synovial chondromatosis is cartilaginous metaplasia of mesenchymal remnants of synovial tissue of the joints. Its main characteristic is the formation of cartilaginous nodules in the synovium and inside the articular space (loose bodies. It usually presents between the third and fifth decades and is rare in children. It presents as a mono-articular pathology affecting large joints such as the knee, hip, and elbow. The main symptoms are pain, swelling, and limitation of movements in the affected joint. Diagnosis is made by panoramic radiographs, computed tomography scan, and mainly magnetic resonance imaging and on surgery. The authors describe of synovial chondromatosis presenting in the elbow of an 11 year-old girl which is unreported to the best of our knowledge.

Osteochondroma and synovial chondromatosis of the temporomandibular joint

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung Eun; Kim, Jae Duk [College of Dentistry, Chosun University, Gwangju (Korea, Republic of)

2002-03-15

Osteochondroma is a benign lesion of osseous and cartilagenous origin. It is a relatively common benign tumor of the skeleton, occurring most often in the metaphyseal region of long bone. However, it is rare in the facial bones. Reported foci in the mandible were the condyle, coronoid process, and symphysis region. Synovial chondromatosis is an uncommon benign condition of unknown etiology which affects the articular joints. Foci of cartilage develop through metaplasia in the underlying connective tissue of the synovial membrane. These cartilagenous foci and fragments may undergo calcification and ossification. We experienced 4 patients with abnormal appearance of mandibular condyle. This report describes 3 cases of osteocondroma and 1 case of synovial chondromatosis of the mandibular condyle with review of the literature

Mimicry of lyme arthritis by synovial hemangioma.

Science.gov (United States)

Hospach, Toni; Langendörfer, M; Kalle, T V; Tewald, F; Wirth, T; Dannecker, G E

2011-12-01

To report on the differential diagnosis of lyme arthritis and synovial hemangioma due to similar clinical and radiological signs and symptoms. A 15-year-old boy presented at the age of 9 with recurrent rather painless swelling of the right knee. Altogether four episodes lasting for 1-2 weeks each occurred over a period of 18 months before medical advice was sought. Physical examination revealed only a slightly limited range of motion. Living in an endemic area of borreliosis, he reported a tick bite 6 months prior to onset of his symptoms with erythema migrans and was treated for 10 days with amoxicillin. Serology revealed two positive unspecific bands in IgG immunoblot (p41 and 66) with slight positivity for ELISA. Ultrasound revealed synovial thickening and increased fluid. Despite the weak positive serology a diagnosis of lyme arthritis could not be excluded and intravenous antibiotic treatment with ceftriaxone was started. After two further relapses antiinflammatory therapy including intraarticular steroids were introduced with no long lasting effect. A chronical disease developed with alternate periods of swelling and almost complete remission. Ultrasound as well as MRI demonstrated ongoing signs of synovitis, therefore after further progression, a diagnostic arthroscopy was performed showing an inconspicuous knee joint. A second MRI showed focal suprapatellar enhancement and was followed by open arthrotomy revealing a histopathological proven synovial cavernous juxtaarticular hemangioma. To our knowledge, the differential diagnosis of lyme arthritis and synovial hemangioma has not yet been reported despite obvious clinical similarities. In conclusion, in children and adolescents synovial hemangioma has to be considered in differential diagnosis of recurrent knee swelling. Early diagnosis is important to prevent prolonged suffering from chronic joint swelling with probable joint damages, unnecessary treatment procedures and as well school and sports

Imaging appearances of synovial plicae syndrome of the knee

Directory of Open Access Journals (Sweden)

Osama Abdalla Mabrouk Kheiralla

2016-08-01

Full Text Available Synovial plicae are synovial folds that may be found as intraarticular structures within the knee joint. They are remnants of incomplete resorption of mesenchymal tissue during fetal development. Synovial plicae, if present, are supposed to be non-pathological and asymptomatic, however if they are exposed to special events like direct trauma or repeated activities, they may be inflamed and become fibrosed and rigid and irritates the synovium of the underlying femoral condyle resulting in secondary mechanical synovitis and chondromalacia leading to what is known as plica syndrome of the knee. Inspite plica syndrome is always suspected on clinical bases and can be clearly visualized by arthroscopic application, still diagnostic imaging by MRI, CT scan and Sonography play important role in the evaluation and diagnosis of this pathological condition. The aim of this article is to provide an overview of the imaging appearances of synovial plicae syndrome of the knee on ultrasound, magnetic resonance imaging (MRI and computerized tomography scan (CT scan.

Synovial sarcoma mimicking benign peripheral nerve sheath tumor

Energy Technology Data Exchange (ETDEWEB)

Larque, Ana B.; Nielsen, G.P.; Chebib, Ivan [Massachusetts General Hospital and Harvard Medical School, Department of Pathology, Boston, MA (United States); Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States)

2017-11-15

To assess the radiographic and clinicopathologic features of synovial sarcoma of the nerve that were clinically or radiologically interpreted as benign peripheral nerve sheath tumor. Five patients with synovial sarcoma arising from the peripheral nerve and interpreted clinically and radiologically as peripheral nerve sheath tumors were identified. Clinicopathologic and imaging features were evaluated. There were three females and two males, ranging in age from 28 to 50 (mean 35.8) years. Most patients (4/5) complained of a mass, discomfort or pain. MR images demonstrated a heterogeneous, enhancing, soft tissue mass contiguous with the neurovascular bundle. On histologic examination, most tumors were monophasic synovial sarcoma (4/5). At the time of surgery, all tumors were noted to arise along or within a peripheral nerve. All patients were alive with no evidence of disease with median follow-up of 44 (range 32-237) months. For comparison, approximately 775 benign peripheral nerve sheath tumors of the extremities were identified during the same time period. Primary synovial sarcoma of the nerve can mimic peripheral nerve sheath tumors clinically and on imaging and should be included in the differential diagnosis for tumors arising from peripheral nerves. (orig.)

Primary Synovial Sarcoma of External Auditory Canal: A Case Report.

Science.gov (United States)

Devi, Aarani; Jayakumar, Krishnannair L L

2017-07-20

Synovial sarcoma is a rare malignant tumor of mesenchymal origin. Primary synovial sarcoma of the ear is extremely rare and to date only two cases have been published in English medical literature. Though the tumor is reported to have an aggressive nature, early diagnosis and treatment may improve the outcome. Here, we report a rare case of synovial sarcoma of the external auditory canal in an 18-year-old male who was managed by chemotherapy and referred for palliation due to tumor progression.

Synovial hemangiomas of the knee: magnetic resonance findings in six cases

International Nuclear Information System (INIS)

Concepcion, L.; Marti-Bonmati, L. M.; Dosda, R.; Llauger, J.; Palmer, J.; Mellado, J. M.

1999-01-01

The synovial hemangioma is an uncommon benign vascular tumor that is difficult to diagnose on the basis of clinical signs Moreover, it has no characteristic radiographic features. The objective of the present report was to describe the MR findings associated with synovial hemangioma of the knee. We review the clinical and MR findings in six patients, with histologically confirmed synovial hemangioma of the Knee, studied with different MR systems and techniques. Synovial hemangiomas were isointense with respect to muscle in T1-weighted images, strongly hyperintense in T2-weighted sequences and presented wavy hypointense linear images. Gadolinium administration resulted in a marked enhancement, although it was heterogeneous in two of three cases analyzed. Although the findings are not pathognomonic, the presence of an intraarticular tumor of the knee that is isointense with respect to muscle in T1 and hyperintense in T2, and shows wavy hypointense images and a marked contrast uptake, may suggest the presence of synovial hemangioma. (Author) 11 refs

Intraarticular volume and clearance in human synovial effusions

International Nuclear Information System (INIS)

Wallis, W.J.; Simkin, P.A.; Nelp, W.B.; Foster, D.M.

1985-01-01

Intraarticular volumes were measured by radiolabeled albumin (RISA) distribution in chronic knee effusions from 11 rheumatoid arthritis patients and 9 osteoarthritis patients. Volumes of synovial fluid obtained at joint aspiration were substantially less than those found by RISA dilution. Up to 24 hours was needed for full distribution of RISA throughout the intraarticular compartment. Measured 123I and RISA radioactivity over the knee described monoexponential rate constants, lambda (minute-1). The clearance of 123I and RISA from synovial effusions was derived by the formulation volume (ml) X lambda (minute-1) = clearance (ml/minute). RISA clearance in rheumatoid effusions was significantly greater than that found in osteoarthritis effusions. Intraarticular volume and isotope clearance were easily quantified and provide measures for further evaluating the microvascular physiology of synovial effusions

Giant primary synovial sarcoma of the anterior mediastinum: A case ...

African Journals Online (AJOL)

2015-06-11

Jun 11, 2015 ... We present a case of primary monophasic synovial sarcoma of the anterior ... Here, we report a case of ... fatigue and anorexia, but no weight loss. ..... Primary intrathoracic synovial sarcoma: A clinicopathologic study of. 40 t (X ...

X-ray, CT and MRI findings of synovial tuberculosis in joints

International Nuclear Information System (INIS)

Yu Jinghong; Tao Meili; You Zhuangzhi; Yu Huazhi

2006-01-01

Objective: To analyze the X-ray, CT and MRI findings of synovial tuberculosis, and to evaluate the role of MRI in diagnosing synovial tuberculosis. Methods: Fourteen cases of synovial tuberculosis comfirmed by operation and pathology were retrospectively analyzed and summarized. All patients were examined by MRI and X-ray, and CT scans were performed in 3 cases. Results: X-ray showed joint swelling (8 cases), articular space narrowing (7 cases), marginal joint erosions (4 cases), and periarticular osteoporosis (9 cases). The joint swelling was detected on CT in all 3 cases, and bony erosion and speckled sequestra were seen in 2 cases. MRI in all of patients showed joint swelling and synovial proliferation in different drgees, demonstrated as heterogeneously low signal on T 1 WI and slight high signal (7 cases) and obvious high signal (6 cases) on T 2 WI, and diffuse synovial proliferation was demonstrated as massive and nodular signal in 8 cases. Joint effusion was present in 7 cases as low signal on T 1 WI and high signal on T 2 WI. Osseous erosion lesions were seen in 7 cases, and intra-articular cartilage thinned, partly or mostly disappeared in 11 cases. Periarticular bone marrow edema was found in 7 cases. Conclusion: MRI was superior to X-ray and CT in the diagnosis and differential diagnosis of synovial tuberculosis. (authors)

Synovial fluid lubrication of artificial joints: protein film formation and composition.

Science.gov (United States)

Fan, Jingyun; Myant, Connor; Underwood, Richard; Cann, Philippa

2012-01-01

Despite design improvements, wear of artificial implants remains a serious health issue particularly for Metal-on-Metal (MoM) hips where the formation of metallic wear debris has been linked to adverse tissue response. Clearly it is important to understand the fundamental lubrication mechanisms which control the wear process. It is usually assumed that MoM hips operate in the ElastoHydrodynamic Lubrication (EHL) regime where film formation is governed by the bulk fluid viscosity; however there is little experimental evidence of this. The current paper critically examines synovial fluid lubrication mechanisms and the effect of synovial fluid chemistry. Two composition parameters were chosen; protein content and pH, both of which are known to change in diseased or post-operative synovial fluid. Film thickness and wear tests were carried out for a series of model synovial fluid solutions. Two distinct film formation mechanisms were identified; an adsorbed surface film and a high-viscosity gel. The entrainment of this gel controls film formation particularly at low speeds. However wear of the femoral head still occurs and this is thought to be due primarily to a tribo-corrosion mechanisms. The implications of this new lubrication mechanism and the effect of different synovial fluid chemistries are examined. One important conclusion is that patient synovial fluid chemistry plays an important role in determining implant wear and the likelihood of failure.

Cystic synovial sarcomas: imaging features with clinical and histopathologic correlation

Energy Technology Data Exchange (ETDEWEB)

Nakanishi, Hirofumi; Araki, Nobuhito [Department of Orthopedic Surgery, Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-Ku, 537-8511, Osaka (Japan); Sawai, Yuka [Department of Radiology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Kudawara, Ikuo [Department of Orthopedic Surgery, Osaka National Hospital, Osaka (Japan); Mano, Masayuki; Ishiguro, Shingo [Department of Pathology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka (Japan); Ueda, Takafumi; Yoshikawa, Hideki [Department of Orthopedic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka (Japan)

2003-12-01

To characterize the radiological and clinicopathologic features of cystic synovial sarcoma. Seven patients with primary cystic synovial sarcoma were evaluated. Computed tomography (CT) and magnetic resonance (MR) imaging were undertaken at the first presentation. The diagnosis of synovial sarcoma was made on the basis of histological examinations followed by molecular analysis. Radiological and clinicopathologic findings were reviewed. CT showed well-defined soft tissue mass without cortical bone erosion and invasion. Calcification was seen at the periphery of the mass in three cases. T2-weighted MR images showed multilocular inhomogeneous intensity mass in all cases, five of which showed fluid-fluid levels. On gross appearance, old and/or fresh hematomas were detected in six cases. In the one remaining case, microscopic hemorrhage in the cystic lumen was proven. Four cases had poorly differentiated areas. In five cases prominent hemangiopericytomatous vasculature was observed. Histologic grade was intermediate in one tumor and high in six. One case had a history of misdiagnosis for tarsal tunnel syndrome, one for lymphadenopathy, two for sciatica and two for hematoma. All cystic synovial sarcomas demonstrated multilocularity with well-circumscribed walls and internal septae. Synovial sarcoma should be taken into consideration in patients with deeply situated multicystic mass with triple signal intensity on T2-weighted MR imaging. (orig.)

Cystic synovial sarcomas: imaging features with clinical and histopathologic correlation

International Nuclear Information System (INIS)

Nakanishi, Hirofumi; Araki, Nobuhito; Sawai, Yuka; Kudawara, Ikuo; Mano, Masayuki; Ishiguro, Shingo; Ueda, Takafumi; Yoshikawa, Hideki

2003-01-01

To characterize the radiological and clinicopathologic features of cystic synovial sarcoma. Seven patients with primary cystic synovial sarcoma were evaluated. Computed tomography (CT) and magnetic resonance (MR) imaging were undertaken at the first presentation. The diagnosis of synovial sarcoma was made on the basis of histological examinations followed by molecular analysis. Radiological and clinicopathologic findings were reviewed. CT showed well-defined soft tissue mass without cortical bone erosion and invasion. Calcification was seen at the periphery of the mass in three cases. T2-weighted MR images showed multilocular inhomogeneous intensity mass in all cases, five of which showed fluid-fluid levels. On gross appearance, old and/or fresh hematomas were detected in six cases. In the one remaining case, microscopic hemorrhage in the cystic lumen was proven. Four cases had poorly differentiated areas. In five cases prominent hemangiopericytomatous vasculature was observed. Histologic grade was intermediate in one tumor and high in six. One case had a history of misdiagnosis for tarsal tunnel syndrome, one for lymphadenopathy, two for sciatica and two for hematoma. All cystic synovial sarcomas demonstrated multilocularity with well-circumscribed walls and internal septae. Synovial sarcoma should be taken into consideration in patients with deeply situated multicystic mass with triple signal intensity on T2-weighted MR imaging. (orig.)

Lipid bilayer membranes: Missing link in the comprehension of synovial lubrication?

Science.gov (United States)

Packard, Ross; Cowley, Leonie; Dubief, Yves

2010-03-01

The human body hosts an extremely efficient tribological system in its synovial joints that operate under very low friction and virtually no wear. It has long been assumed that the higher molecular weight molecules present in the synovial fluid (hyaluronic acid, lubricin) are solely responsible for the mechanical properties of joint. Smaller components, unsaturated phospholipids, have a virtually an undefined role, most probably because of the cancellation of their amphiphilic properties ex vivo caused by oxidation. Using experimental observations of multilamellar arrangements in synovial joints, we formulate the assumption that self-assembling structures provide the anisotropy necessary to synovial fluid to resist drainage under normal compression. Our molecular dynamics simulations demonstrate the tremendous mechanical properties of lipid bilayers and also highlight their weakening consistent with modifications resulting from injuries or joint prosthesis.

Microarchitecture and protective mechanisms in synovial tissue from clinically and arthroscopically normal knee joints

NARCIS (Netherlands)

Smith, M. D.; Barg, E.; Weedon, H.; Papengelis, V.; Smeets, T.; Tak, P. P.; Kraan, M.; Coleman, M.; Ahern, M. J.

2003-01-01

Background: Synovial biopsies are used to study synovial immunopathology and are increasingly applied for the evaluation of new therapeutic strategies in chronic arthritis. Therefore, it is essential to be informed on the complete spectrum of synovial immunopathology. Objective: To describe the

Giant primary synovial sarcoma of the anterior mediastinum: A case ...

African Journals Online (AJOL)

Primary synovial sarcoma is a very rare tumor of the mediastinum, which is unreported in the entire subcontinent of West Africa, and presents daunting challenges from diagnosis to management with lack of standard management strategies. We present a case of primary monophasic synovial sarcoma of the anterior ...

Hip Synovial Fluid Cell Counts in Children From a Lyme Disease Endemic Area.

Science.gov (United States)

Dart, Arianna H; Michelson, Kenneth A; Aronson, Paul L; Garro, Aris C; Lee, Thomas J; Glerum, Kimberly M; Nigrovic, Peter A; Kocher, Mininder S; Bachur, Richard G; Nigrovic, Lise E

2018-05-01

Patients with septic hip arthritis require surgical drainage, but they can be difficult to distinguish from patients with Lyme arthritis. The ability of synovial fluid white blood cell (WBC) counts to help discriminate between septic and Lyme arthritis of the hip has not been investigated. We assembled a retrospective cohort of patients ≤21 years of age with hip monoarticular arthritis and a synovial fluid culture obtained who presented to 1 of 3 emergency departments located in Lyme disease endemic areas. Septic arthritis was defined as a positive synovial fluid culture result or synovial fluid pleocytosis (WBC count ≥50 000 cells per µL) with a positive blood culture result. Lyme arthritis was defined as positive 2-tiered Lyme disease serology results and negative synovial fluid bacterial culture results. All other patients were classified as having other arthritis. We compared median synovial fluid WBC counts by arthritis type. Of the 238 eligible patients, 26 (11%) had septic arthritis, 32 (13%) had Lyme arthritis, and 180 (76%) had other arthritis. Patients with septic arthritis had a higher median synovial fluid WBC count (126 130 cells per µL; interquartile range 83 303-209 332 cells per µL) than patients with Lyme arthritis (53 955 cells per µL; interquartile range 33 789-73 375 cells per µL). Eighteen patients (56%) with Lyme arthritis had synovial fluid WBC counts ≥50 000 cells per µL. Of the 94 patients who underwent surgical drainage, 13 were later diagnosed with Lyme arthritis. In Lyme disease endemic areas, synovial fluid WBC counts cannot always help differentiate septic from Lyme arthritis. Rapid Lyme diagnostics could help avoid unnecessary operative procedures in patients with Lyme arthritis. Copyright © 2018 by the American Academy of Pediatrics.

Involvement of DNA polymerase δ in DNA repair synthesis in human fibroblasts at late times after ultraviolet irradiation

International Nuclear Information System (INIS)

Dresler, S.L.; Gowans, B.J.; Robinson-Hill, R.M.; Hunting, D.J.

1988-01-01

DNA repair synthesis following UV irradiation of confluent human fibroblasts has a biphasic time course with an early phase of rapid nucleotide incorporation and a late phase of much slower nucleotide incorporation. The biphasic nature of this curve suggests that two distinct DNA repair systems may be operative. Previous studies have specifically implicated DNA polymerase δ as the enzyme involved in DNA repair synthesis occurring immediately after UV damage. In this paper, the authors describe studies of DNA polymerase involvement in DNA repair synthesis in confluent human fibroblasts at late times after UV irradiation. Late UV-induced DNA repair synthesis in both intact and permeable cells was found to be inhibited by aphidicolin, indicating the involvement of one of the aphidicolin-sensitive DNA polymerases, α or δ. In permeable cells, the process was further analyzed by using the nucleotide analogue (butylphenyl)-2'-deoxyguanosine 5'-triphosphate, which inhibits DNA polymerase α several hundred times more strongly than it inhibits DNA polymerase δ. The (butylphenyl)-2'-deoxyguanosine 5'-triphosphate inhibition curve for late UV-induced repair synthesis was very similar to that for polymerase δ. It appears that repair synthesis at late time after UV irradiation, like repair synthesis at early times, is mediated by DNA polymerase δ

Intermetatarsal bursa primary synovial chondromatosis. Case report and review of the literature

Energy Technology Data Exchange (ETDEWEB)

Trevino, Manuel; Laks, Shaked; Sundarakumar, Dinesh K.; Smith, Crysela M. [Texas Tech Univ. Health Science Center, El Paso, TX (United States). Dept. of Radiology; Kafchinski, Lisa [Texas Tech Univ. Health Science Center, El Paso, TX (United States). Dept. of Orthopedic Surgery and Rehabilitation

2017-12-15

Primary synovial chondromatosis is a benign neoplastic process, occurring mostly in large joints, more rarely in tendon sheaths, and extremely uncommonly in bursae. We describe a patient with primary synovial chondromatosis arising in the fourth intermetatarsal bursa. Knowledge of the bursal anatomy of the forefoot, and of characteristic imaging findings and the pathogenesis of synovial chondromatosis, is essential in including this uncommon entity in the differential when occurring in unusual locations. (orig.)

Autoimmune Th17 Cells Induced Synovial Stromal and Innate Lymphoid Cell Secretion of the Cytokine GM-CSF to Initiate and Augment Autoimmune Arthritis.

Science.gov (United States)

Hirota, Keiji; Hashimoto, Motomu; Ito, Yoshinaga; Matsuura, Mayumi; Ito, Hiromu; Tanaka, Masao; Watanabe, Hitomi; Kondoh, Gen; Tanaka, Atsushi; Yasuda, Keiko; Kopf, Manfred; Potocnik, Alexandre J; Stockinger, Brigitta; Sakaguchi, Noriko; Sakaguchi, Shimon

2018-06-19

Despite the importance of Th17 cells in autoimmune diseases, it remains unclear how they control other inflammatory cells in autoimmune tissue damage. Using a model of spontaneous autoimmune arthritis, we showed that arthritogenic Th17 cells stimulated fibroblast-like synoviocytes via interleukin-17 (IL-17) to secrete the cytokine GM-CSF and also expanded synovial-resident innate lymphoid cells (ILCs) in inflamed joints. Activated synovial ILCs, which expressed CD25, IL-33Ra, and TLR9, produced abundant GM-CSF upon stimulation by IL-2, IL-33, or CpG DNA. Loss of GM-CSF production by either ILCs or radio-resistant stromal cells prevented Th17 cell-mediated arthritis. GM-CSF production by Th17 cells augmented chronic inflammation but was dispensable for the initiation of arthritis. We showed that GM-CSF-producing ILCs were present in inflamed joints of rheumatoid arthritis patients. Thus, a cellular cascade of autoimmune Th17 cells, ILCs, and stromal cells, via IL-17 and GM-CSF, mediates chronic joint inflammation and can be a target for therapeutic intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

Synovial Tissue Response to Treatment with TNF Blockers in Peripheral Spondyloarthritis

NARCIS (Netherlands)

Paramarta, Jacqueline E.; Baeten, Dominique; de Rycke, Leen

2011-01-01

This review describes the synovial response to treatment in peripheral spondyloarthritis (SpA). A series of recent studies demonstrates that the synovial histopathology is largely homogenous between different SpA subtypes and can be strongly modulated by effective treatment such as tumor necrosis

Characterization of the porcine synovial fluid proteome and a comparison to the plasma proteome

Directory of Open Access Journals (Sweden)

Tue Bjerg Bennike

2015-12-01

In addition, we analyzed the proteome of human plasma, and compared the proteomes to the obtained porcine synovial fluid proteome. The proteome of the two body fluids were found highly similar, underlining the detected plasma derived nature of many synovial fluid components. The healthy porcine synovial fluid proteomics data, human rheumatoid arthritis synovial fluid proteomics data used in the method optimization, human plasma proteomics data, and search results, have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD000935.

[Passage of nonsteroidal anti-inflammatory agents across the synovial membrane].

Science.gov (United States)

Netter, P; Bannwarth, B; Monot, C; Royer, R J; Gaucher, A

1983-09-24

The therapeutic effectiveness of non-steroid anti-inflammatory (NSAI) drugs is partly determined by their passage across the synovial membrane. The synovium can be compared to a double barrier the permeability of which to NSAI drugs depends on the degree of inflammation of the joint and on the pharmacokinetic properties of the drugs (lipophilia, pka, protein-binding). A few hours after one single systemic dose, concentrations in the synovial fluid are higher than in serum. During chronic administration, concentrations of NSAI drugs with a short half-life vary less in synovial fluid than in serum. During steady state, free fractions of NSAI drugs with prolonged half-life may be similar in both compartments.

Thoracic Synovial Cyst at the Th2-3 Level Causing Myelopathy

DEFF Research Database (Denmark)

Sundskarð, Martin M; Gaini, Shahin

2017-01-01

Intraspinal synovial cyst is a rare cause of myelopathy. These cysts present most often in the lumbar and cervical parts of the spine but are more infrequent in the thoracic spine. We present a case of a 73-year-old man with an intraspinal, extradural synovial cyst at the Th2-3 level causing...... paraesthesia and weakness in the legs. A laminectomy and excision of the cyst were performed and the patient recovered fully. In the thoracic spine, synovial cysts are almost exclusively found in the lower part. Laminectomy, with excision, is the treatment of choice, although steroid injections have been...

Condromatose sinovial Synovial chondromatosis

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Neylor Pace Lasmar

2010-01-01

the site. He was referred to a knee specialist with a suspected meniscal injury. Upon examination, we detected severe swelling of the joint with limitation of motion, pain exacerbated, and negative joint aspiration. Since simple radiographic results were normal, an MRI of the knee was requested. The MRI revealed massive accumulation of synovial fluid, together with marked synovial proliferation, especially focal thickening clumps with intermediate signal on T1 and T2, a hypointense signal on T2, and discreet suggestive of pigmented villonodular synovitis with intact meniscus and ligaments. The patient underwent arthroscopy of the left knee, which revealed whitish irregular fragments, and underwent arthrotomy with removal of the lesion and extensive synovectomy. The material was submitted to pathological examination, which showed the presence of synovial chondromatosis. Eight months after surgery, the patient presents with no complaints, with a 130° range in the left knee without joint bleeding or signs of inflammation. Synovial chondromatosis is a rare benign metaplasia of the synovial membrane, leading to the formation of cartilaginous loose bodies in the joint space. It is difficult to diagnose because 95% of the nodules, when not calcified, can be overlooked radiologically.

Differential involvement of synovial adipokines in pain and physical function in female patients with knee osteoarthritis. A cross-sectional study.

Science.gov (United States)

Calvet, J; Orellana, C; Albiñana Giménez, N; Berenguer-Llergo, A; Caixàs, A; García-Manrique, M; Galisteo Lencastre, C; Navarro, N; Larrosa, M; Gratacós, J

2018-02-01

Adipokines have been reported to play a role in the development, progression and severity of knee osteoarthritis but the influence of the different adipokines are not well known. The aim of this study was to evaluate the association between different synovial fluid adipokines with pain and disability knee osteoarthritis patients. Cross-sectional study with systematic inclusion of 115 symptomatic primary knee osteoarthritis female patients with ultrasound-confirmed joint effusion. Age, physical exercise, symptoms duration and different anthropometric measurements were collected. Radiographic severity was evaluated according to Kellgren-Lawrence scale. Pain and disability were assessed by WOMAC-total, -pain, -function subscales and Knee injury and Osteoarthritis Outcome Score (KOOS) pain and function scales. Seven adipokines and three inflammatory markers were measured by ELISA in synovial fluid. Partial Correlation Coefficient (PCC) and corresponding 95% confidence interval were used as a measure of association. Leptin, osteopontin and inflammatory factors, especially TNF-alpha, were associated to pain and function. After adjustment for potential confounders including inflammatory factors and all adipokines, an association was found for adiponectin with pain (PCC 0.240 [0.012, 0.444]) and for resistin and visfatin with function (PCC 0.336 [0.117, 0.524] and -0.262 [-0.463, -0.036]). No other adipokines or inflammatory markers were statistically and independently associated. An association between physical exercise and pain and disability remained after adjustment, whereas an attenuation of the influence of anthropometric measurements was observed. Different patterns of association between synovial fluid adipokines were observed regarding pain and disability in knee osteoarthritis patients. Specifically, adiponectin was associated to pain while resistin and visfatin were mainly related to function. Copyright © 2017 Osteoarthritis Research Society International

Receptor Protein Tyrosine Phosphatase α-Mediated Enhancement of Rheumatoid Synovial Fibroblast Signaling and Promotion of Arthritis in Mice

NARCIS (Netherlands)

Stanford, Stephanie M; Svensson, Mattias N D; Sacchetti, Cristiano; Pilo, Caila A; Wu, Dennis J; Kiosses, William B; Hellvard, Annelie; Bergum, Brith; Muench, German R Aleman; Elly, Christian; Liu, Yun-Cai; den Hertog, Jeroen; Elson, Ari; Sap, Jan; Mydel, Piotr; Boyle, David L; Corr, Maripat; Firestein, Gary S; Bottini, Nunzio

OBJECTIVE: During rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) critically promote disease pathogenesis by aggressively invading the extracellular matrix of the joint. The focal adhesion kinase (FAK) signaling pathway is emerging as a contributor to the anomalous behavior of RA FLS.

TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants and arrests downstream differentiation at an early stage of hypertrophy.

Science.gov (United States)

Shintani, Nahoko; Siebenrock, Klaus A; Hunziker, Ernst B

2013-01-01

Synovial explants furnish an in-situ population of mesenchymal stem cells for the repair of articular cartilage. Although bone morphogenetic protein 2 (BMP-2) induces the chondrogenesis of bovine synovial explants, the cartilage formed is neither homogeneously distributed nor of an exclusively hyaline type. Furthermore, the downstream differentiation of chondrocytes proceeds to the stage of terminal hypertrophy, which is inextricably coupled with undesired matrix mineralization. With a view to optimizing BMP-2-induced chondrogenesis, the modulating influences of fibroblast growth factor 2 (FGF-2) and transforming growth factor beta 1 (TGF-ß1) were investigated. Explants of bovine calf metacarpal synovium were exposed to BMP-2 (200 ng/ml) for 4 (or 6) weeks. FGF-2 (10 ng/ml) or TGF-ß1 (10 ng/ml) was introduced at the onset of incubation and was present either during the first week of culturing alone or throughout its entire course. FGF-2 enhanced the BMP-2-induced increase in metachromatic staining for glycosaminoglycans (GAGs) only when it was present during the first week of culturing alone. TGF-ß1 enhanced not only the BMP-2-induced increase in metachromasia (to a greater degree than FGF-2), but also the biochemically-assayed accumulation of GAGs, when it was present throughout the entire culturing period; in addition, it arrested the downstream differentiation of cells at an early stage of hypertrophy. These findings were corroborated by an analysis of the gene- and protein-expression levels of key cartilaginous markers and by an estimation of individual cell volume. TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants, improves the hyaline-like properties of the neocartilage, and arrests the downstream differentiation of cells at an early stage of hypertrophy. With the prospect of engineering a mature, truly articular type of cartilage in the context of clinical repair, our findings will be of importance in fine-tuning the

TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants and arrests downstream differentiation at an early stage of hypertrophy.

Directory of Open Access Journals (Sweden)

Nahoko Shintani

Full Text Available Synovial explants furnish an in-situ population of mesenchymal stem cells for the repair of articular cartilage. Although bone morphogenetic protein 2 (BMP-2 induces the chondrogenesis of bovine synovial explants, the cartilage formed is neither homogeneously distributed nor of an exclusively hyaline type. Furthermore, the downstream differentiation of chondrocytes proceeds to the stage of terminal hypertrophy, which is inextricably coupled with undesired matrix mineralization. With a view to optimizing BMP-2-induced chondrogenesis, the modulating influences of fibroblast growth factor 2 (FGF-2 and transforming growth factor beta 1 (TGF-ß1 were investigated.Explants of bovine calf metacarpal synovium were exposed to BMP-2 (200 ng/ml for 4 (or 6 weeks. FGF-2 (10 ng/ml or TGF-ß1 (10 ng/ml was introduced at the onset of incubation and was present either during the first week of culturing alone or throughout its entire course. FGF-2 enhanced the BMP-2-induced increase in metachromatic staining for glycosaminoglycans (GAGs only when it was present during the first week of culturing alone. TGF-ß1 enhanced not only the BMP-2-induced increase in metachromasia (to a greater degree than FGF-2, but also the biochemically-assayed accumulation of GAGs, when it was present throughout the entire culturing period; in addition, it arrested the downstream differentiation of cells at an early stage of hypertrophy. These findings were corroborated by an analysis of the gene- and protein-expression levels of key cartilaginous markers and by an estimation of individual cell volume.TGF-ß1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants, improves the hyaline-like properties of the neocartilage, and arrests the downstream differentiation of cells at an early stage of hypertrophy. With the prospect of engineering a mature, truly articular type of cartilage in the context of clinical repair, our findings will be of importance in fine-tuning the

Scintigraphic presentation of hip joint synovial chondromatosis

Energy Technology Data Exchange (ETDEWEB)

Zwas, S T; Friedman, B; Nerubay, J

1988-09-01

A case of hip joint synovial chondromatosis with an unusual scintigraphic pattern is described. This pattern was suggestive of a hip joint destructive reactive articular process or late manifestations of avascular necrosis of the femoral head. Concurrent radiographs were normal, as were laboratory investigations. Follow-up radiographs six months later showed radiolucencies and erosive bone changes in the diseased joint. Surgical and histopathological findings revealed well developed hip synovial chondromatosis (HSC) with thickened synovium and large, loose, cartilaginous bodies occupying and widening the tightened joint space, with destructive secondary juxta articular pressure and bone erosions. This and other scintigraphic patterns in HSC, and the differential diagnosis of the findings in patients with painful hip presentations are discussed.

Synovial calprotectin: a potential biomarker to exclude a prosthetic joint infection.

Science.gov (United States)

Wouthuyzen-Bakker, M; Ploegmakers, J J W; Kampinga, G A; Wagenmakers-Huizenga, L; Jutte, P C; Muller Kobold, A C

2017-05-01

Recently, several synovial biomarkers have been introduced into the algorithm for the diagnosis of a prosthetic joint infection (PJI). Alpha defensin is a promising biomarker, with a high sensitivity and specificity, but it is expensive. Calprotectin is a protein that is present in the cytoplasm of neutrophils, is released upon neutrophil activation and exhibits anti-microbial activity. Our aim, in this study, was to determine the diagnostic potential of synovial calprotectin in the diagnosis of a PJI. In this pilot study, we prospectively collected synovial fluid from the hip, knee, shoulder and elbow of 19 patients with a proven PJI and from a control group of 42 patients who underwent revision surgery without a PJI. PJI was diagnosed according to the current diagnostic criteria of the Musculoskeletal Infection Society. Synovial fluid was centrifuged and the supernatant was used to measure the level of calprotectin after applying a lateral flow immunoassay. The median synovial calprotectin level was 991 mg/L (interquartile range (IQR) 154 to 1787) in those with a PJI and 11 mg/L (IQR 3 to 29) in the control group (p infection. With a lateral flow immunoassay, a relatively rapid quantitative diagnosis can be made. The measurement is cheap and is easy to use. Cite this article: Bone Joint J 2017;99-B:660-5. ©2017 The British Editorial Society of Bone & Joint Surgery.

Development of a Synthetic Synovial Fluid for Tribological Testing

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Emely Lea Bortel

2015-12-01

Full Text Available Wear tests of joint prostheses are usually performed using bovine calf serum. The results from different laboratories are hardly ever comparable as, for example, the protein concentration and the protein composition of the serum-based test liquids vary. In addition, the viscosity of these test liquids is similar to that of water and does not match the more viscous synovial fluid. The present work was aimed at developing a synthetic synovial fluid as an alternative to the existing test liquids. Improved consistency and reproducibility of results at a similar price were required. Hyaluronic acid (HA, the lyophilized proteins bovine serum albumin (BSA and immunoglobulin G (IgG, the phospholipid lecithin (PL and salts were applied in a stepwise approach to replace the actually used test liquid based on newborn calf serum. The in vitro results obtained with ultra-high-molecular-weight polyethylene (UHMWPE pins sliding against CoCrMo discs revealed that the developed synthetic synovial fluid fulfils the set requirements: increase of viscosity, reasonable cost, improved consistency and wear particles which resemble the ones found in vivo. The developed synthetic synovial fluid with 3 g/L HA, 19 g/L BSA, 11 g/L IgG, 0.1 g/L PL and Ringer solution is a more realistic alternative to the used serum-based test liquid.

Fibroblasts in fibrosis: novel roles and mediators

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Ryan Thomas Kendall

2014-05-01

Full Text Available Fibroblasts are the most common cell type of the connective tissues found throughout the body and the principal source of the extensive extracellular matrix (ECM characteristic of these tissues. They are also the central mediators of the pathological fibrotic accumulation of ECM and the cellular proliferation and differentiation that occurs in response to prolonged tissue injury and chronic inflammation. The transformation of the fibroblast cell lineage involves classical developmental signaling programs and includes a surprisingly diverse range of precursor cell types—most notably, myofibroblasts that are the apex of the fibrotic phenotype. Myofibroblasts display exaggerated ECM production; constitutively secrete and are hypersensitive to chemical signals such as cytokines, chemokines, and growth factors; and are endowed with a contractile apparatus allowing them to manipulate the ECM fibers physically to close open wounds. In addition to ECM production, fibroblasts have multiple concomitant biological roles, such as in wound healing, inflammation, and angiogenesis, which are each interwoven with the process of fibrosis. We now recognize many common fibroblast-related features across various physiological and pathological protracted processes. Indeed, a new appreciation has emerged for the role of noncancerous fibroblast interactions with tumors in cancer progression. Although the predominant current clinical treatments of fibrosis involve nonspecific immunosuppressive and anti-proliferative drugs, a variety of potential therapies under investigation specifically target fibroblast biology.

A rare case of synovial sarcoma of the prostate | Dhabalia | African ...

African Journals Online (AJOL)

Prostatic synovial sarcomas are exceedingly rare. To our knowledge, only six primary cases have been reported so far. We herein describe a primary synovial sarcoma of the prostate seen in a 25- year-old male patient, the youngest patient seen with this disease to date. He was referred to our department with the diagnosis ...

Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis.

Science.gov (United States)

Zhang, Wenyao; Li, Xuezhong; Xu, Tong; Ma, Mengru; Zhang, Yong; Gao, Ming-Qing

2016-11-15

Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. Copyright © 2016 Elsevier Inc. All rights reserved.

Transforming growth factor β1 enhances heme oxygenase 1 expression in human synovial fibroblasts by inhibiting microRNA 519b synthesis.

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Shu-Jui Kuo

Full Text Available Osteoarthritis (OA is manifested by synovial inflammation and cartilage destruction that is directly linked to synovitis, joint swelling and pain. In the light of the role of synovium in the pathogenesis and the symptoms of OA, synovium-targeted therapy is a promising strategy to mitigate the symptoms and progression of OA. Transforming growth factor beta 1 (TGF-β1, a secreted homodimeric protein, possesses unique and potent anti-inflammatory and immune-regulatory properties in many cell types. Heme oxygenase 1 (HO-1 is an inducible anti-inflammatory and stress responsive enzyme that has been proven to prevent injuries caused by many diseases. Despite the similar anti-inflammatory profile and their involvement in the pathogenesis of arthritic diseases, no studies have as yet explored the possibility of any association between the expression of TGF-β1 and HO-1.TGF-β1-induced HO-1 expression was examined by HO-1 promoter assay, qPCR, and Western blotting. The siRNAs and enzyme inhibitors were utilized to determine the intermediate involved in the signal transduction pathway. We showed that TGF-β1 stimulated the synthesis of HO-1 in a concentration- and time-dependent manner, which can be mitigated by blockade of the phospholipase (PLCγ/protein kinase C alpha (PKCα pathway. We also showed that the expression of miRNA-519b, which blocks HO-1 transcription, is inhibited by TGF-β1, and the suppression of miRNA 519b could be reversed via blockade of the PLCγ/PKCα pathway.TGF-β1 stimulated the expression of HO-1 via activating the PLCγ/PKCα pathway and suppressing the downstream expression of miRNA-519b. These results may shed light on the pathogenesis and treatment of OA.

Value of CT scan in synovial diseases

Energy Technology Data Exchange (ETDEWEB)

Tamisier, J.N.; Regent, D.; Thomas, P.; Pere, P.; Gaucher, A.; Capesius, P.

1986-02-01

The authors have developed a technique of CT arthroscan which, by the use of a gas or opaque contrast medium, is able to demonstrate the synovial structures of the knee, the shoulder and the hip. Among the essential indications, they include the demonstration of neoplasia of the synovium and the evaluation of the pannus in rheumatoid arthritis. Their secondary indications include the demonstration of fluid effusions in the hip, the precise evaluation of hyperostotic lesions in the same joint, the detection of ossification phenomena in the capsule of the inter-apophyseal joints in ankylosing spondylitis and, in some cases, following negative or doubtful arthrography for the detection of synovial plica. They also recall the usefulness or the arthroscan in the diagnosis of lesions of the labrum glenoidale.

MiR-338-5p Promotes Inflammatory Response of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Targeting SPRY1.

Science.gov (United States)

Yang, Yan; Wang, Yanfeng; Liang, Qingwei; Yao, Lutian; Gu, Shizhong; Bai, Xizhuang

2017-08-01

Our purpose is to study the roles of microRNA-338-5p (miR-338-5p) on the proliferation, invasion, and inflammatory response of fibroblast-like synoviocytes (SFs) in rheumatoid arthritis patients by regulating SPRY1. The target relationship between miR-338-5p and SPRY1 was validated through luciferase reporter system. The expression of miR-338-5p and SPRY1 in synovial tissues and synovial cells were detected using RT-PCR and western blot. The mimics and inhibitors of miR-338-5p were transfected into SFs. MTT, Transwell, and ELISA assays were used to analyze cell proliferation, invasiveness, and the secreted extracellular pro-inflammatory cytokines (such as IL-1a, IL-6, COX2) levels of SFs. MiR-338-5p was highly expressed in rheumatoid arthritis tissues and cells, and directly down-regulated the expression of SPRY1 in the SFs of rheumatoid arthritis patients. Cell proliferation, invasiveness and the expression level of pro-inflammatory cytokines in synovial cells increased after the transfection of miR-338-5p mimics, while the proliferation, invasion and expression level of pro-inflammatory cytokines decreased after the transfection of miR-338-5p inhibitors. In conclusion,miR-338-5p promoted the proliferation, invasion and inflammatory reaction in SFs of rheumatoid arthritis by directly down-regulating SPRY1 expression. J. Cell. Biochem. 118: 2295-2301, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Hydrogen sulphide decreases IL-1β-induced activation of fibroblast-like synoviocytes from patients with osteoarthritis

Science.gov (United States)

Sieghart, Daniela; Liszt, Melissa; Wanivenhaus, Axel; Bröll, Hans; Kiener, Hans; Klösch, Burkhard; Steiner, Günter

2015-01-01

Balneotherapy employing sulphurous thermal water is still applied to patients suffering from diseases of musculoskeletal system like osteoarthritis (OA) but evidence for its clinical effectiveness is scarce. Since the gasotransmitter hydrogen sulphide (H2S) seems to affect cells involved in degenerative joint diseases, it was the objective of this study to investigate the effects of exogenous H2S on fibroblast-like synoviocytes (FLS), which are key players in OA pathogenesis being capable of producing pro-inflammatory cytokines and matrix degrading enzymes. To address this issue primary FLS derived from OA patients were stimulated with IL-1β and treated with the H2S donor NaHS. Cellular responses were analysed by ELISA, quantitative real-time PCR, phospho-MAPkinase array and Western blotting. Treatment-induced effects on cellular structure and synovial architecture were investigated in three-dimensional extracellular matrix micromasses. NaHS treatment reduced both spontaneous and IL-1β-induced secretion of IL-6, IL-8 and RANTES in different experimental settings. In addition, NaHS treatment reduced the expression of matrix metallo-proteinases MMP-2 and MMP-14. IL-1β induced the phosphorylation of several MAPkinases. NaHS treatment partially reduced IL-1β-induced activation of several MAPK whereas it increased phosphorylation of pro-survival factor Akt1/2. When cultured in spherical micromasses, FLS intentionally established a synovial lining layer-like structure; stimulation with IL-1β altered the architecture of micromasses leading to hyperplasia of the lining layer which was completely inhibited by concomitant exposure to NaHS. These data suggest that H2S partially antagonizes IL-1β stimulation via selective manipulation of the MAPkinase and the PI3K/Akt pathways which may encourage development of novel drugs for treatment of OA. PMID:25312962

Synovial chondromatosis and osteochondroma in TMJ with CBCT images

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Seo, Yo Seob; Lee, Gun Sun; Kim, Jin Soo; Kim, Jae Duk [Department of Oral and Maxilloficial Radiology, School of Dentistry, Oral Biology Research Institute, Chosun University, Gwangju (Korea, Republic of)

2010-03-15

Synovial chondromatosis is an uncommon disorder characterized by metaplastic formation of multiple cartilaginous and osteocartilaginous nodules within connective tissue of the synovial membrane of joints. Osteochondroma is a benign lesion of osseous and cartilagenous origin. It is frequently found in the general skeleton, but is rare in the mandibular condyle. We experienced 2 patients with abnormal appearance of temporomandibular joint. Histologic diagnoses were not obtained, because surgery was unwarranted in view of the lack of symptoms and the benign differential diagnosis. We describes 2 cases that show the characteristics of both disease simultaneously.

Persistent Amplification of DNA Damage Signal Involved in Replicative Senescence of Normal Human Diploid Fibroblasts

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Masatoshi Suzuki

2012-01-01

Full Text Available Foci of phosphorylated histone H2AX and ATM are the surrogate markers of DNA double strand breaks. We previously reported that the residual foci increased their size after irradiation, which amplifies DNA damage signals. Here, we addressed whether amplification of DNA damage signal is involved in replicative senescence of normal human diploid fibroblasts. Large phosphorylated H2AX foci (>1.5 μm diameter were specifically detected in presenescent cells. The frequency of cells with large foci was well correlated with that of cells positive for senescence-associated β-galactosidase staining. Hypoxic cell culture condition extended replicative life span of normal human fibroblast, and we found that the formation of large foci delayed in those cells. Our immuno-FISH analysis revealed that large foci partially localized at telomeres in senescent cells. Importantly, large foci of phosphorylated H2AX were always colocalized with phosphorylated ATM foci. Furthermore, Ser15-phosphorylated p53 showed colocalization with the large foci. Since the treatment of senescent cells with phosphoinositide 3-kinase inhibitor, wortmannin, suppressed p53 phosphorylation, it is suggested that amplification of DNA damage signaling sustains persistent activation of ATM-p53 pathway, which is essential for replicative senescence.

Primary synovial sarcoma of the abdominal wall: A case report and review of the literature

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Alsaif H Saif

2008-01-01

Full Text Available Synovial sarcoma is a malignant mesenchymal neoplasm which commonly occurs in the extremities of adults, in close association with joint capsules, tendon sheaths, bursae and fascial structures. Only a few cases of synovial sarcoma occurring in the abdominal wall have been reported. A case of a primary synovial sarcoma arising from the anterior abdominal wall fascial aponeurosis is presented.

Evaluation of the anti-inflammatory actions of various functional food materials including glucosamine on synovial cells.

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Yamagishi, Yoshie; Someya, Akimasa; Imai, Kensuke; Nagao, Junji; Nagaoka, Isao

2017-08-01

The anti-inflammatory actions of glucosamine (GlcN) on arthritic disorders involve the suppression of inflammatory mediator production from synovial cells. GlcN has also been reported to inhibit the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. The present study aimed to determine the cooperative and anti‑inflammatory actions of functional food materials and evaluated the production of interleukin (IL)‑8 and phosphorylation of p38 MAPK in IL-1β-activated synovial cells, incubated with the combination of GlcN and various functional food materials containing L‑methionine (Met), undenatured type II collagen (UC‑II), chondroitin sulfate (CS), methylsulfonylmethane (MSM) and agaro-oligosaccharide (AO). The results indicated that Met, UC‑II, CS, MSM and AO slightly or moderately suppressed the IL-1β-stimulated IL‑8 production by human synovial MH7A cells. The same compounds further decreased the IL‑8 level lowered by GlcN. Similarly, they slightly suppressed the phosphorylation level of p38 MAPK and further reduced the phosphorylation level lowered by GlcN. These observations suggest a possibility that these functional food materials exert an anti‑inflammatory action (inhibition of IL‑8 production) in combination with GlcN by cooperatively suppressing the p38 MAPK signaling (phosphorylation).

Increased uptake of sup(99m)Tc-MDP in calcified synovial sarcoma

International Nuclear Information System (INIS)

Horne, T.; Mogle, P.; Finsterbush, A.; Gordin, M.; Hadassah Univ. Hospital, Mount Scopus; Hadassah Univ. Hospital, Mount Scopus

1983-01-01

We present a case of a partially calcified synovial sarcoma of the soft tissues of the thigh in a young girl. The roentgenographic, arteriographic and radio-nuclide scans were unusual. The finding and possible causes of increased uptake of sup(99m)Tc-MDP in synovial sarcoma are discussed. (orig.)

SYNOVIAL CHONDROMATOSIS OF THE TEMPORO-MANDIBULAR JOINT. A CASE REPORT

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V. MALANCHUK

2015-09-01

Full Text Available The study describes a rare clinical case of synovial chondromatosis of the temporo-mandibular joint, in a 53 year-old patient. In the prehospital stage, the patient was examined by additional diagnostic methods – 3D CT and subsequent computer simulation, in view of subsequent surgery. In January 2015, partial synovektomy of the right temporo-mandibular joint with removal of cartilaginous impurities was performed under general anesthesia. After histopathological confirmation of the clinical diagnosis, the patient was discharged in satisfactory condition, with recommendations for further examination and radiological control. Synovial chondromatosis of the temporo-mandibular joint is a disease characterized by impaired formation of cartilage or of intraarticular, cartilaginous, and relatively rare bone impurities. An important role in the diagnosis of joints’ synovial chondromatosis is played by the instrumental research methods, especially X-ray. Surgical treatment is recommended as a function of the prevalence of lesions.

Value of CT scan in synovial diseases

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Tamisier, J.N.; Regent, D.; Thomas, P.; Pere, P.; Gaucher, A.; Capesius, P.

1986-01-01

The authors have developed a technique of CT arthroscan which, by the use of a gas or opaque contrast medium, is able to demonstrate the synovial structures of the knee, the shoulder and the hip. Among the essential indications, they include the demonstration of neoplasia of the synovium and the evaluation of the pannus in rheumatoid arthritis. Their secondary indications include the demonstration of fluid effusions in the hip, the precise evaluation of hyperostotic lesions in the same joint, the detection of ossification phenomena in the capsule of the inter-apophyseal joints in ankylosing spondylitis and, in some cases, following negative or doubtful arthrography for the detection of synovial plica. They also recall the usefulness or the arthroscan in the diagnosis of lesions of the labrum glenoidale [fr

The effect of contrast media on the synovial membrane

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Papacharalampous, Xenophon [Department of Radiology, University of Athens, Vasilissis Sofias 76 Ave., GR-115 28 Athens (Greece)]. E-mail: medgraph@otenet.gr; Patsouris, Efstratios [Department of Pathology, University of Athens, Mikras Asias 75 str., GR-115 27 Athens (Greece); Mundinger, Alexander [Clinic of Radiology, Marienhospital Osnabrueck, Johannisfreiheit 2-4, D-49074 Osnabruek (Germany); Beck, Andreas [Clinic of Radiology, Konstanz, Luisenstrasse 7, D-78461 Konstanz (Germany); Kouloulias, Vasilios [Department of Radiotherapy, University of Athens, Vasilissis Sofias 76 Ave., GR-115 28 Athens (Greece); Primetis, Elias [Department of Radiology, University of Athens, Vasilissis Sofias 76 Ave., GR-115 28 Athens (Greece); Koureas, Andreas [Department of Radiology, University of Athens, Vasilissis Sofias 76 Ave., GR-115 28 Athens (Greece); Vlahos, Lambros [Department of Radiology, University of Athens, Vasilissis Sofias 76 Ave., GR-115 28 Athens (Greece)

2005-09-01

Objective: To examine the effect of intra-articular injection of contrast media, sorbitol and normal saline on the synovial membrane. Materials and methods: Sixty three rabbits (126 knees) were used in this study. We injected the knees with amidotrizoate, ioxaglate, iopamidol, iotrol and diluted gadolinium-DTPA (2 mmol/l). Normal saline and sorbitol 27.25% were used for comparison. A histological and histochemical examination of the knees was carried out 1, 2, 10, 20, 30, 40 and 60 days after the injection. Results: On histological examination, the knees injected with normal saline, ioxaglate and gadolinium-DTPA had a normal appearance. Intra-articular injection of amidotrizoate, iopamidol, iotrol and sorbitol caused early, mild and transient histological changes of the synovium (synovial hyperplasia, infiltration by leucocytes). Furthermore, the knees injected with amidotrizoate presented with late, extensive histological changes (severe synovial hyperplasia, moderate vascular dilatation, severe infiltration by leukocytes). Conclusion: The results suggest that the chemical structure and not the osmolality of the contrast media is the main cause for the histological changes of the synovium.

Synovial chondromatosis of the temporomandibular joint.

Science.gov (United States)

Reyes Macías, Juan Francisco; Sánchez Prieto, Martín

2007-01-01

Synovial Chondromatosis (SC) is a disease whose etiology is unknown, can be defined as a benign synovial process characterized by the formation of metaplastic cartilaginous nodes inside connective tissue of articular surfaces, is considered an active metaplastic phenomenon better than a neoplastic process; it presents a greater preference to affect women who constitute almost 70% of reported cases, the age range is wide and oscillates between 18-75 years (average 44.6 years). Between the main clinical findings are: pain, crackle, volume augmentation and a limited buccal opening. SC is an unusual state and the reports in the English literature are no more than 75 cases, only 66 of those where histologically verified, most of those were affecting great joints like hip, knee and shoulder, but if SC is not frequent in this sites, is even more infrequent on temporomandibular joint. The aim of this paper is to report a clinical case and at the same time to realize a brief review of the literature.

Feasibility of a tetracycline-binding method for detecting synovial fluid basic calcium phosphate crystals.

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Rosenthal, Ann K; Fahey, Mark; Gohr, Claudia; Burner, Todd; Konon, Irina; Daft, Laureen; Mattson, Eric; Hirschmugl, Carol; Ryan, Lawrence M; Simkin, Peter

2008-10-01

Basic calcium phosphate (BCP) crystals are common components of osteoarthritis (OA) synovial fluid. Progress in understanding the role of these bioactive particles in clinical OA has been hampered by difficulties in their identification. Tetracyclines stain calcium phosphate mineral in bone. The aim of this study was to investigate whether tetracycline staining might be an additional or alternative method for identifying BCP crystals in synovial fluid. A drop of oxytetracycline was mixed with a drop of fluid containing synthetic or native BCP, calcium pyrophosphate dihydrate (CPPD), or monosodium urate (MSU) crystals and placed on a microscope slide. Stained and unstained crystals were examined by light microscopy, with and without a portable broad-spectrum ultraviolet (UV) pen light. A small set of characterized synovial fluid samples were compared by staining with alizarin red S and oxytetracycline. Synthetic BCP crystals in synovial fluid were quantified fluorimetrically using oxytetracycline. After oxytetracycline staining, synthetic and native BCP crystals appeared as fluorescent amorphous aggregates under UV light. Oxytetracycline did not stain CPPD or MSU crystals or other particulates. Oxytetracycline staining had fewer false-positive test results than did alizarin red S staining and could provide estimates of the quantities of synthetic BCP crystals in synovial fluid. With further validation, oxytetracycline staining may prove to be a useful adjunct or alternative to currently available methods for identifying BCP crystals in synovial fluid.

Inhibition of oncostatin M in osteoarthritic synovial fluid enhances GAG production in osteoarthritic cartilage repair

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M Beekhuizen

2013-09-01

Full Text Available Mediators in the synovial fluid are thought to play a major role in osteoarthritic cartilage turnover. The purpose of the current study was to investigate the role of oncostatin M (OSM in osteoarthritis (OA by evaluating the presence of the cytokine and its receptors in the OA joint and interfering with its activity in synovial fluid co-cultured with cartilage explants. OSM levels were increased in the synovial fluid of osteoarthritic patients compared to healthy donors. Immunohistochemistry confirmed the presence of both the leukaemia inhibitory factor (LIF and OSM receptors for OSM throughout the whole depth of osteoarthritic cartilage and synovial tissue, whereas in healthy cartilage their presence seemed more restricted to the superficial zone. Blocking OSM activity, using an activity inhibiting antibody, in 25 % osteoarthritic synovial fluid added to OA cartilage explant cultures increased glycosaminoglycan (GAG content from 18.6 mg/g to 24.3 mg/g (P < 0.03 and total production from 7.0 mg/g to 11.9 mg/g (P < 0.003. However, OSM exogenously added to cartilage explant cultures reflecting low and high concentrations in the synovial fluid (5 and 50 pg/mL did not affect cartilage matrix turnover, suggesting that factors present in the synovial fluid act in concert with OSM to inhibit GAG production. The current study indicates the potential to enhance cartilage repair in osteoarthritis by modulating the joint environment by interfering with OSM activity.

Doppler ultrasound imaging techniques for assessment of synovial inflammation

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Filippucci E

2013-09-01

Full Text Available Emilio Filippucci,1 Fausto Salaffi,1 Marina Carotti,2 Walter Grassi1 1Rheumatology Department, Polytechnic University of the Marche, Ancona, Italy; 2Department of Radiology, Polytechnic University of the Marche, Ancona, Italy Abstract: Ultrasound is an evolving technique, and the rapid progress made in ultrasound technology over the past ten years has dramatically increased its range of applications in rheumatology. One of the most exciting advances is the use of Doppler ultrasound imaging in the assessment of blood flow abnormalities at the synovial tissue level in patients with chronic inflammatory arthritis. This review describes the Doppler techniques available and their main applications in patients with inflammatory arthritis, discusses the evidence supporting their use, and outlines the latest advances in hardware and software. Spectral, color, and power Doppler allow sensitive assessment of vascular abnormalities at the synovial tissue level. Use of contrast agents enhances visualization of the small synovial vessels using color or power Doppler ultrasound and allows for accurate characterization of the rheumatoid pannus. Doppler techniques represent a unique method for assessment of synovial inflammation, showing blood flow characteristics in real time. They are safe, noninvasive, cost-effective, and have high sensitivity in revealing and monitoring synovitis. However, several questions still need to be answered. In the near future, the Doppler techniques described here, together with upcoming hardware and software facilities, will be investigated further and a consensus will be reached on their feasibility and appropriate use in daily rheumatologic practice. Keywords: power and color Doppler techniques, ultrasound, contrast media, synovitis, rheumatoid arthritis

β1-Integrin Expression in the Rheumatoid Synovial-Pannus Formation

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Ishikawa, Hitoshi; Hirata, Soichiro; Isobe, Takashi; Nishibayashi, Yasurou; Kubo, Hitoshi; Nannbae, Masahiro; Nakagawa, Natsuko; Andoh, Yoshihiro

1994-01-01

In order to investigate the mechanism of synovial pannus formation in rheumatoid arthritis, using an immunohistochemical staining technique with monoclonal antibodies against adhesion molecules, anti-CDw49a (VLA-1), CDw49b (VLA-2), CDw49c (VLA-3), CDw49d (VLA-4) and CDw49e (VLA-5), the pattern of distribution of these molecules at the rheumatoid synovial cartilage junction has been investigated. Twelve samples of rheumatoid articular cartilage covered with pannus were examined. Treatment with...

Synovial sarcoma of the kidney in a young patient with a review of the literature

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Mahmoud Abbas

2014-06-01

Full Text Available Synovial sarcoma (SS is a soft tissue, generally deep seated neoplasms that occurs generally in the proximity of large joints. We report of a case of a 33-year-old man who was diagnosed with primary SS of the kidney which is an extremely rare tumor that accounts for less than 2% of malignant renal tumors. Contemporary management of renal synovial sarcoma includes surgical resection and ifosfamide-based chemotherapy and they remain the mainstay of therapy of synovial sarcoma, which is often applied, combined as part of an aggressive treatment approach. Fewer than 50 patients have been described in the English literature. Physicians should be aware of the possibility of malignancy in cystic renal masses and raise the suspicion of synovial sarcoma, especially when patients with renal masses are young adults. Along with the case report a literature review on primary synovial sarcomas of the kidney is provided with focus on the renal tumors’ differential diagnosis.

Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis

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Zhang, Wenyao; Li, Xuezhong; Xu, Tong; Ma, Mengru [College of Veterinary Medicine, Northwest A& F University, Yangling 712100, Shaanxi (China); Zhang, Yong, E-mail: zhangyong1956@nwsuaf.edu.cn [College of Veterinary Medicine, Northwest A& F University, Yangling 712100, Shaanxi (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100, Shaanxi (China); Gao, Ming-Qing, E-mail: gaomingqing@nwsuaf.edu.cn [College of Veterinary Medicine, Northwest A& F University, Yangling 712100, Shaanxi (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100, Shaanxi (China)

2016-11-15

Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. - Highlights: • Inflammatory BMEs affect the properties of BMFs during mastitis. • BMEs inhibited the proliferation and promoted the migration of BMFs. • BMEs enhanced secretion of inflammatory mediators and deposition of ECM in BMFs. • Changes of the properties of BMFs were mediated by specific signal molecules.

Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis

International Nuclear Information System (INIS)

Zhang, Wenyao; Li, Xuezhong; Xu, Tong; Ma, Mengru; Zhang, Yong; Gao, Ming-Qing

2016-01-01

Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. - Highlights: • Inflammatory BMEs affect the properties of BMFs during mastitis. • BMEs inhibited the proliferation and promoted the migration of BMFs. • BMEs enhanced secretion of inflammatory mediators and deposition of ECM in BMFs. • Changes of the properties of BMFs were mediated by specific signal molecules.

Plasma pharmacokinetics and synovial concentrations of S-flurbiprofen plaster in humans.

Science.gov (United States)

Yataba, Ikuko; Otsuka, Noboru; Matsushita, Isao; Kamezawa, Miho; Yamada, Ichimaro; Sasaki, Sigeru; Uebaba, Kazuo; Matsumoto, Hideo; Hoshino, Yuichi

2016-01-01

The purpose of this study is to investigate the pharmacokinetics and deep tissue penetration capability of the newly developed S-flurbiprofen plaster (SFPP) in humans. Study 1: SFPP tape-type patch (2-60 mg) was applied to the lower back for 24 h in healthy adult volunteers. S-flurbiprofen (SFP) plasma concentration was measured over time to examine SFP pharmacokinetics. Study 2: SFPP (20 mg) was applied for 12 h to the affected knee of osteoarthritis (OA) patients who were scheduled for total knee arthroplasty. Deep tissues (synovial tissue and synovial fluid) were collected during surgery to compare SFP concentrations after application of SFPP or a commercially available flurbiprofen (FP) gel-type patch. Study 1: The plasma concentration of SFP was sustained during 24-h topical application of the SFPP, showing a high percutaneous absorption ratio of 51.4-72.2 %. Cmax and AUC0-∞ were dose-proportional. Study 2: After application of the SFPP for 12 h, SFP concentrations in the synovial tissue and synovial fluid were 14.8-fold (p = 0.002) and 32.7-fold (p < 0.001) higher, respectively, than those achieved by the FP patch. Sustained plasma concentration of SFP and high percutaneous absorption ratio was observed after 24-h topical application of the SFPP. Compared to the FP patch, the SFPP showed superior percutaneous absorption and greater tissue penetration of SFP into the synovial tissue. Greater tissue penetration of the SFPP seemed to be primarily due to its formulation. Thus, SFPP is expected to show higher efficacy for the treatment of knee OA.

Arthroscopic resection of humeroradial synovial plica for persistent lateral elbow pain.

Science.gov (United States)

Rajeev, Aysha; Pooley, Joesph

2015-04-01

To review the outcome of 121 patients who underwent arthroscopic resection of a humeroradial synovial plica for persistent lateral elbow pain. 92 men and 29 women aged 24 to 56 (mean, 38) years with chronic lateral elbow pain underwent arthroscopic resection of a humeroradial synovial plica using a motorised soft tissue shaver, followed by intensive physiotherapy. The modified elbow score and range of motion were assessed, as were wound healing, infection, soft tissue swelling or effusion, tenderness, ligamentous instability, and motor strength. No patient had any ligamentous instability. 80 patients were pain-free at 3 months; only 3 patients were taking pain medication at 6 months. All patients had full pronation and supination; the mean range of motion was 3º to 135º of flexion. The mean modified elbow score at 12 months was 93.2 (range, 72-100). The percentages of patients with excellent, good, fair, and poor score were 70%, 17%, 8%, and 5% at 3 months, 74%, 20%, 3%, and 3% at 6 months, and 76%, 18%, 3%, and 3% at 12 months, respectively. A humeroradial synovial plica is one of the causes of chronic lateral elbow pain. Arthroscopic resection of the synovial plica followed by intensive physiotherapy achieved good outcome.

JOINT INVOLVEMENT IN SYPHILIS

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T. I. Zlobina

2016-01-01

Full Text Available Joint involvement in syphilis has been considered as casuistry in recent years. At the same time, the high incidence of primary syphilis and the notified cases of late neurosyphilis may suggest that joint involvement in this disease is by no means always verified. Traditionally there are two forms of syphilitic arthritis: primary synovial (involving the articular membranes and sac and primary bone (involving the articular bones and cartilages ones. The paper describes the authors' clinical case of the primary bone form of articular syphilis in a 34-year-old man. 

Gadolinium Contrast Agent is of Limited Value for Magnetic Resonance Imaging Assessment of Synovial Hypertrophy in Hemophiliacs

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Lundin, B.; Berntorp, E.; Pettersson, H.; Wirestam, R.; Jonsson, K.; Staahlberg, F.; Ljung, R. [Dept. of Radiology, Univ Hospital of Lund, Lund (Sweden)

2007-07-15

Purpose: To examine the influence of different doses of gadolinium contrast agent on synovial enhancement, to compare magnetic resonance imaging (MRI) findings of synovial hypertrophy and radiographic joint changes in hemophiliacs, and to investigate the value of gadolinium in MRI assessment of synovial hypertrophy in hemophiliacs using dynamic MRI and MRI scoring. Material and Methods: Twenty-one hemophiliacs on prophylactic factor treatment without recent bleeds were subjected to radiography and gadolinium contrast-enhanced dynamic and static MRI of the knee using a standard dose of 0.1 mmol/kg b.w. gadoteridol. In 17 of the patients, the MRI procedure was repeated after a triple dose of gadoteridol. Results: MRI findings of synovial hypertrophy were significantly correlated with Pettersson radiographic scores. In 19 of the 21 MRI investigated joints, administration of contrast agent did not alter the result of the evaluation of synovial hypertrophy. Conclusion: The optimal time interval for volume assessment of synovial hypertrophy after injection of gadolinium contrast agent is dose dependent. Hemophiliacs without recent bleeds have minor to abundant synovial hypertrophy in joints with pronounced radiographic changes. Dynamic MRI is not useful for evaluating hemophilic arthropathy, and gadolinium contrast agent is not routinely indicated for MRI scoring of joints in hemophiliacs.

Gadolinium Contrast Agent is of Limited Value for Magnetic Resonance Imaging Assessment of Synovial Hypertrophy in Hemophiliacs

International Nuclear Information System (INIS)

Lundin, B.; Berntorp, E.; Pettersson, H.; Wirestam, R.; Jonsson, K.; Staahlberg, F.; Ljung, R.

2007-01-01

Purpose: To examine the influence of different doses of gadolinium contrast agent on synovial enhancement, to compare magnetic resonance imaging (MRI) findings of synovial hypertrophy and radiographic joint changes in hemophiliacs, and to investigate the value of gadolinium in MRI assessment of synovial hypertrophy in hemophiliacs using dynamic MRI and MRI scoring. Material and Methods: Twenty-one hemophiliacs on prophylactic factor treatment without recent bleeds were subjected to radiography and gadolinium contrast-enhanced dynamic and static MRI of the knee using a standard dose of 0.1 mmol/kg b.w. gadoteridol. In 17 of the patients, the MRI procedure was repeated after a triple dose of gadoteridol. Results: MRI findings of synovial hypertrophy were significantly correlated with Pettersson radiographic scores. In 19 of the 21 MRI investigated joints, administration of contrast agent did not alter the result of the evaluation of synovial hypertrophy. Conclusion: The optimal time interval for volume assessment of synovial hypertrophy after injection of gadolinium contrast agent is dose dependent. Hemophiliacs without recent bleeds have minor to abundant synovial hypertrophy in joints with pronounced radiographic changes. Dynamic MRI is not useful for evaluating hemophilic arthropathy, and gadolinium contrast agent is not routinely indicated for MRI scoring of joints in hemophiliacs

Sciatica as the first manifestation of synovial sarcoma. Contribution of magnetic resonance imaging to the diagnosis

International Nuclear Information System (INIS)

Veillard, E.; Le Dantec, P.; Chales, G.; Jean, S.; Pawlotsky, Y.

1995-01-01

A 38-year-old man presented with paralyzing sciatica as the first manifestation of synovial sarcoma of his right leg. Although neurologic symptoms sometimes occur as manifestations of synovial sarcoma, they are exceptionally inaugural. Magnetic resonance imaging is a valuable tool in patients with synovial tumors, both for establishing the diagnosis and for evaluating the extent of the lesion. (authors). 13 refs., 3 figs

CDCP1 identifies a CD146 negative subset of marrow fibroblasts involved with cytokine production.

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Mineo Iwata

Full Text Available In vitro expanded bone marrow stromal cells contain at least two populations of fibroblasts, a CD146/MCAM positive population, previously reported to be critical for establishing the stem cell niche and a CD146-negative population that expresses CUB domain-containing protein 1 (CDCP1/CD318. Immunohistochemistry of marrow biopsies shows that clusters of CDCP1+ cells are present in discrete areas distinct from areas of fibroblasts expressing CD146. Using a stromal cell line, HS5, which approximates primary CDCP1+ stromal cells, we show that binding of an activating antibody against CDCP1 results in tyrosine-phosphorylation of CDCP1, paralleled by phosphorylation of Src Family Kinases (SFKs Protein Kinase C delta (PKC-δ. When CDCP1 expression is knocked-down by siRNA, the expression and secretion of myelopoietic cytokines is increased. These data suggest CDCP1 expression can be used to identify a subset of marrow fibroblasts functionally distinct from CD146+ fibroblasts. Furthermore the CDCP1 protein may contribute to the defining function of these cells by regulating cytokine expression.

The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis

Science.gov (United States)

Boyle, D L; Soma, K; Hodge, J; Kavanaugh, A; Mandel, D; Mease, P; Shurmur, R; Singhal, A K; Wei, N; Rosengren, S; Kaplan, I; Krishnaswami, S; Luo, Z; Bradley, J; Firestein, G S

2015-01-01

Objective Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). The pathways affected by tofacitinib and the effects on gene expression in situ are unknown. Therefore, tofacitinib effects on synovial pathobiology were investigated. Methods A randomised, double-blind, phase II serial synovial biopsy study (A3921073; NCT00976599) in patients with RA with an inadequate methotrexate response. Patients on background methotrexate received tofacitinib 10 mg twice daily or placebo for 28 days. Synovial biopsies were performed on Days -7 and 28 and analysed by immunoassay or quantitative PCR. Clinical response was determined by disease activity score and European League Against Rheumatism (EULAR) response on Day 28 in A3921073, and at Month 3 in a long-term extension study (A3921024; NCT00413699). Results Tofacitinib exposure led to EULAR moderate to good responses (11/14 patients), while placebo was ineffective (1/14 patients) on Day 28. Tofacitinib treatment significantly reduced synovial mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-3 (pTofacitinib significantly decreased plasma CXCL10 (pTofacitinib reduces metalloproteinase and interferon-regulated gene expression in rheumatoid synovium, and clinical improvement correlates with reductions in STAT1 and STAT3 phosphorylation. JAK1-mediated interferon and interleukin-6 signalling likely play a key role in the synovial response. Trial registration number NCT00976599. PMID:25398374

Percutaneous biopsy of the synovial membrane of large joints

International Nuclear Information System (INIS)

Begule, V.

1989-01-01

Using flouroscopy, the authors have developed new techniques of percutaneous synovial biopsy (PSB) of large joints of limbs (other than the knee). PSB was performed on outpatients under local anesthesia. They have performed 84 biopsies (hips: 57), shoulders: 10, elbows: six, wrists: five, ankles: six). The PSB technique was gradually improved. Main technical refinements were use of a Tru-Cut needle introduced through a Jamshidi trephine needle, placement of the cutting window parallel to the anterior aspect of the joint, and selection of an optimal approach and biopsy site. With these improvements, the success rate of attaining synovial membrane was raised from 49% to 81%. No complications were encountered

Synovial Osteochondromatosis at the Carpometacarpal Joint of the Thumb

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Satoru Yonekura

2017-01-01

Full Text Available Synovial osteochondromatosis (SOC is a benign tumor characterized by synovial connective tissue metaplasia. SOC commonly affects major joints including the knee followed by the hip, elbow, and wrist. SOC cases in the hand are not reported as often as SOC of major joints. Particularly SOC of the carpometacarpal joint of the thumb is rare. We report on a 57-year-old female with primary SOC of the carpometacarpal joint of her left thumb. Surgical excision was performed and the patient had no symptoms with full range of motion of her left thumb. At 3 years of follow-up, there was no recurrence.

Invasiveness of fibroblast-like synoviocytes is an individual patient characteristic associated with the rate of joint destruction in patients with rheumatoid arthritis.

Science.gov (United States)

Tolboom, Tanja C A; van der Helm-Van Mil, Annette H M; Nelissen, Rob G H H; Breedveld, Ferdinand C; Toes, René E M; Huizinga, Tom W J

2005-07-01

Rheumatoid arthritis (RA) is characterized by inflammation and destruction of synovial joints. Fibroblast-like synoviocytes (FLS) harvested from synovial tissue of patients with RA can invade normal human cartilage in severe combined immunodeficient (SCID) mice and Matrigel basement membrane matrix in vitro. This study was undertaken to investigate the association of these in vitro characteristics with disease characteristics in patients with RA. Synovial tissue samples from 72 RA and 49 osteoarthritis (OA) patients were obtained. Samples of different joints were collected from 7 patients with RA. The FLS invasiveness in Matrigel was studied, and the intraindividual and interindividual differences were compared. From the patients with FLS who exhibited the most extreme differences in in vitro ingrowth (most and least invasive FLS), radiographs of the hands and feet were collected and scored according to the Sharp/van der Heijde method to determine the relationship between in vitro invasion data and estimated yearly joint damage progression. FLS from patients with RA were more invasive than FLS from patients with OA (P patient characteristic. The mean +/- SEM Sharp score on radiographs of the hands or feet divided by the disease duration was 4.4 +/- 1.1 units per year of disease duration in patients with the least invasive FLS (n = 9), which was much lower compared with the 21.8 +/- 3.1 units per year of disease duration in patients with the most invasive FLS (n = 9) (P patient characteristic, given the much smaller intraindividual than interindividual FLS variation.

Fibroblast growth factor 23

African Journals Online (AJOL)

Dr Olaleye

Systemic phosphate homeostasis is maintained through several hormonal mechanisms which involve fibroblast growth factor 23 (FGF-23), α-klotho, vitamin D and parathyroid hormone. FGF-23 is known to be the major regulator of phosphate balance (Mirams et al., 2004). FGF-23 is a phosphaturic hormone, which is.

Mesenchymal Stem/Progenitor Cells Derived from Articular Cartilage, Synovial Membrane and Synovial Fluid for Cartilage Regeneration: Current Status and Future Perspectives.

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Huang, Yi-Zhou; Xie, Hui-Qi; Silini, Antonietta; Parolini, Ornella; Zhang, Yi; Deng, Li; Huang, Yong-Can

2017-10-01

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.

A rapid screen for four corticosteroids in equine synovial fluid.

Science.gov (United States)

Agrawal, Karan; Ebel, Joseph G; Bischoff, Karyn

2014-06-01

Most antidoping method development in the equine industry has been for plasma and urine, though there has been recent interest in the analysis of synovial fluid for evidence of doping by intra-articular corticosteroid injection. Published methods for corticosteroid analysis in synovial fluid are primarily singleplex methods, do not screen for all corticosteroids of interest and are not adequately sensitive. The purpose of this study is to develop a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) screening method for the detection of four of the most common intra-articularly administered corticosteroids--betamethasone, methylprednisolone, methylprednisolone acetate and triamcinolone acetonide. Sample preparation consisted of protein precipitation followed by a basified liquid-liquid extraction. LC-MS-MS experiments consisted of a six-min isocratic separation using a Phenomenex Polar-RP stationary phase and a mobile phase consisting of 35% acetonitrile, 5 mM ammonium acetate and 0.1% formic acid in nanopure water. The detection system used was a triple quadrupole mass analyzer with thermospray ionization, and compounds were identified using selective reaction monitoring. The method was validated to the ISO/IEC 17025 standard, and real synovial fluid samples were analyzed to demonstrate the application of the method in an antidoping context. The method was highly selective for the four corticosteroids with limits of detection of 1-3 ng/mL. The extraction efficiency was 50-101%, and the matrix effects were 14-31%. These results indicate that the method is a rapid and sensitive screen for the four corticosteroids in equine synovial fluid, fit for purpose for equine antidoping assays.

Ultrasound guided synovial biopsy of the wrist

NARCIS (Netherlands)

van Vugt, R. M.; van Dalen, A.; Bijlsma, J. W.

1997-01-01

Seven patients (4 female and 3 male, mean age 46) with arthritis of the wrist (n = 7) without known etiology were evaluated. High-definition ultrasound equipment was used for localization of synovial hypertrophy, suitable for ultrasound guided biopsy without risk. A 18-gauge diameter Tru-cut biopsy

Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress

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Olga Loseva

2014-07-01

Full Text Available The risks of non-cancerous diseases associated with exposure to low doses of radiation are at present not validated by epidemiological data, and pose a great challenge to the scientific community of radiation protection research. Here, we show that premature senescence is induced in human fibroblasts when exposed to chronic low dose rate (LDR exposure (5 or 15 mGy/h of gamma rays from a 137Cs source. Using a proteomic approach we determined differentially expressed proteins in cells after chronic LDR radiation compared to control cells. We identified numerous proteins involved in protection against oxidative stress, suggesting that these pathways protect against premature senescence. In order to further study the role of oxidative stress for radiation induced premature senescence, we also used human fibroblasts, isolated from a patient with a congenital deficiency in glutathione synthetase (GS. We found that these GS deficient cells entered premature senescence after a significantly shorter time of chronic LDR exposure as compared to the GS proficient cells. In conclusion, we show that chronic LDR exposure induces premature senescence in human fibroblasts, and propose that a stress induced increase in reactive oxygen species (ROS is mechanistically involved.

Matrix metalloproteinase activity and prostaglandin E2 are elevated in the synovial fluid of meniscus tear patients.

Science.gov (United States)

Liu, Betty; Goode, Adam P; Carter, Teralyn E; Utturkar, Gangadhar M; Huebner, Janet L; Taylor, Dean C; Moorman, Claude T; Garrett, William E; Kraus, Virginia B; Guilak, Farshid; DeFrate, Louis E; McNulty, Amy L

Meniscus tears are a common knee injury and are associated with the development of post-traumatic osteoarthritis (OA). The purpose of this study is to evaluate potential OA mediators in the synovial fluid and serum of meniscus tear subjects compared to those in the synovial fluid of radiographic non-OA control knees. Sixteen subjects with an isolated unilateral meniscus injury and six subjects who served as reference controls (knee Kellgren-Lawrence grade 0-1) were recruited. Twenty-one biomarkers were measured in serum from meniscus tear subjects and in synovial fluid from both groups. Meniscus tear subjects were further stratified by tear type to assess differences in biomarker levels. Synovial fluid total matrix metalloproteinase (MMP) activity and prostaglandin E2 (PGE2) were increased 25-fold and 290-fold, respectively, in meniscus tear subjects as compared to reference controls (p meniscus tear subjects (R = 0.83, p meniscus tear subjects, synovial fluid levels of MMP activity, MMP-2, MMP-3, sGAG, COMP, IL-6, and PGE2 were higher than serum levels (p meniscus tears had higher synovial fluid MMP-10 (p meniscus injury may be targets to promote meniscus repair and prevent OA development.

Blockade of Toll-like receptor 2 prevents spontaneous cytokine release from rheumatoid arthritis ex vivo synovial explant cultures

LENUS (Irish Health Repository)

Nic An Ultaigh, Sinead

2011-02-23

Abstract Introduction The aim of this study was to examine the effect of blocking Toll-like receptor 2 (TLR2) in rheumatoid arthritis (RA) synovial cells. Methods RA synovial tissue biopsies, obtained under direct visualization at arthroscopy, were established as synovial explant cultures ex vivo or snap frozen for immunohistology. Mononuclear cell cultures were isolated from peripheral blood and synovial fluid of RA patients. Cultures were incubated with the TLR1\\/2 ligand, Pam3CSK4 (200 ng, 1 and 10 μg\\/ml), an anti-TLR2 antibody (OPN301, 1 μg\\/ml) or an immunoglobulin G (IgG) (1 μg\\/ml) matched control. The comparative effect of OPN301 and adalimumab (anti-tumour necrosis factor alpha) on spontaneous release of proinflammatory cytokines from RA synovial explants was determined using quantitative cytokine MSD multiplex assays or ELISA. OPN301 penetration into RA synovial tissue explants cultures was assessed by immunohistology. Results Pam3CSK4 significantly upregulated interleukin (IL)-6 and IL-8 in RA peripheral blood mononuclear cells (PBMCs), RA synovial fluid mononuclear cells (SFMCs) and RA synovial explant cultures (P < 0.05). OPN301 significantly decreased Pam3CSK4-induced cytokine production of tumour necrosis factor alpha (TNF-α), IL-1β, IL-6, interferon (IFN)-γ and IL-8 compared to IgG control in RA PBMCs and SFMCs cultures (all P < 0.05). OPN301 penetration of RA synovial tissue cultures was detected in the lining layer and perivascular regions. OPN301 significantly decreased spontaneous cytokine production of TNF-α, IL-1β, IFN-γ and IL-8 from RA synovial tissue explant cultures (all P < 0.05). Importantly, the inhibitory effect of OPN on spontaneous cytokine secretion was comparable to inhibition by anti-TNFα monoclonal antibody adalimumab. Conclusions These findings further support targeting TLR2 as a potential therapeutic agent for the treatment of RA.

Analysis of synovial fluid components of hydrarthrosis in long-term hemodialysis patients.

Science.gov (United States)

Shiota, E; Maekawa, M; Ohtani, M

1999-01-01

The synovial fluid components in long-term hemodialysis patients (HD; 43 knees in 43 patients) were investigated and compared with those in patients with osteoarthritis (OA; 21 knees in 21 patients) and rheumatoid arthritis (RA; 26 knees in 26 patients). The average ages in the three groups were, respectively, 60.7 years (range, 34-79 years), 63.2 years (range, 48-88 years), and 59.7 years (range, 37-76 years). The duration of hemodialysis in the HD group averaged 14.0 years (range, 4-24 years). The concentrations of hyaluronic acid, protein, and isomers of chondroitin sulfate (chondroitin 6-sulfate [C6S] and chondroitin 4-sulfate [C4S]) in the synovial fluid, and its viscosity were measured. Differences in each of the parameters were investigated according to disease clinical stage, roentgenological grade, and periods of dialysis in the HD group. The viscosity of the synovial fluid and the concentration of hyaluronic acid in HD patients were similar to those in OA patients; however, the C6S/C4S ratio in the synovial fluid of HD patients was similar to that in RA patients. The latter finding suggests that synovitis may be present in the hydrarthrosis of HD patients. The cause of this synovitis in HD patients remains to be elucidated.

MR tomography of hemophilic osteoarthropathy with special reference to synovial and chondrogenic alterations

International Nuclear Information System (INIS)

Erlemann, R.; Pollmann, H.; Vestring, T.; Peters, P.E.

1992-01-01

52 knee and ankle joints of hemophiliacs were examined by MRI using FLASH and FISP-3-D sequences; and the degree of synovial hypertrophy and of cartilage destruction were assessed. Findings of synovial hypertrophy varied between thin membranes and tumorous tissue destroying the joint cartilage. Degree of cartilage destruction varied between focal signal decrease and total loss. In spite of recurrent joint bleedings no synovial or cartilaginous changes were seen in 31% and 29% of joints, respectively. Changes were more frequently seen and degree was more marked in the ankle than in the knee joints. With the exception of cysts, osseous destruction was more obvious with radiographs. MRI is suitable for the investigation of joints of hemophiliacs showing no osseous destruction. (orig.) [de

OSTEOCHONDROMA OF THE PROXIMAL HUMERUS WITH FRICTIONAL BURSITIS AND SECONDARY SYNOVIAL OSTEOCHONDROMATOSIS.

Science.gov (United States)

De Groote, J; Geerts, B; Mermuys, K; Verstraete, K

2015-01-01

We report a case of multiple hereditary exostosis in a 33-year old patient with clinical symptoms of pain and impression of a growing mass of the left shoulder alerting potential risk of malignant transformation of an osteochondroma. Imaging studies illustrated perilesional bursitis surrounding an osteochondroma of the proximal humerus. Malignant transformation was excluded with MRI. Fragments of the osteochondroma were dislocated in the inflammatory synovial bursa illustrating a case of secondary synovial osteochondromatosis.

Synovial sarcoma of the foot

International Nuclear Information System (INIS)

Beus, J.; Kreitner, K.F.; Rompe, J.D.; Riehle, H.M.

1996-01-01

The case of a 29 year-old female patient who had experienced pain in the right midfoot for 5 years which was diagnosed as a degenerative or rheumatic change and treated by physiotherapy and medication. By means of magnetic resonance imaging we identified a soft-tissue tumor of the midfoot. Histology provided the findings of a monophasic fibrous synovial sarcoma. The case history is reported together with a presentation of the disease and its radiological diagnosis. (orig.) [de

Inner Synovial Membrane Footprint of the Anterior Elbow Capsule: An Arthroscopic Boundary

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Srinath Kamineni

2015-01-01

Full Text Available Introduction. The purpose of this study is to describe the inner synovial membrane (SM of the anterior elbow capsule, both qualitatively and quantitatively. Materials and Methods. Twenty-two cadaveric human elbows were dissected and the distal humerus and SM attachments were digitized using a digitizer. The transepicondylar line (TEL was used as the primary descriptor of various landmarks. The distance between the medial epicondyle and medial SM edge, SM apex overlying the coronoid fossa, the central SM nadir, and the apex of the SM insertion overlying the radial fossa and distance from the lateral epicondyle to lateral SM edge along the TEL were measured and further analyzed. Gender and side-to-side statistical comparisons were calculated. Results. The mean age of the subjects was 80.4 years, with six male and five female cadavers. The SM had a distinctive double arched attachment overlying the radial and coronoid fossae. No gender-based or side-to-side quantitative differences were noted. In 18 out of 22 specimens (81.8%, an infolding extension of the SM was observed overlying the medial aspect of the trochlea. The SM did not coincide with the outer fibrous attachment in any specimen. Conclusion. The humeral footprint of the synovial membrane of the anterior elbow capsule is more complex and not as capacious as commonly understood from the current literature. The synovial membrane nadir between the two anterior fossae may help to explain and hence preempt technical difficulties, a reduction in working arthroscopic volume in inflammatory and posttraumatic pathologies. This knowledge should allow the surgeon to approach this aspect of the anterior elbow compartment space with the confidence that detachment of this synovial attachment, to create working space, does not equate to breaching the capsule. Alternatively, stripping the synovial attachment from the anterior humerus does not constitute an anterior capsular release.

Synovial cyst of the hip joint as a rare cause of unlateral leg edema; A case report

Energy Technology Data Exchange (ETDEWEB)

Kang, Ji Hun; Chang, Il Soo; Park, Sang Woo; Yun, Ik Jin; Park, Hyung Kyu; Kim, Wan Seop; Lee, Hui Jin; Kim, Na Ra; Moon, Sung Gyu [Konkuk University School of Medicine, Seoul (Korea, Republic of)

2015-06-15

A synovial cyst of the hip joint is a rare cause of unilateral leg edema, and it is usually associated with arthropathies such as rheumatoid arthritis and osteoarthritis. An asymptomatic synovial cyst of the hip joint that is not associated with an arthritic condition occurs infrequently. In this paper, we described the case of a 52-year-old woman who presented with unilateral right leg edema caused by a synovial cyst of the hip joint.

Pathology of experimental Ebola virus infection in African green monkeys. Involvement of fibroblastic reticular cells.

Science.gov (United States)

Davis, K J; Anderson, A O; Geisbert, T W; Steele, K E; Geisbert, J B; Vogel, P; Connolly, B M; Huggins, J W; Jahrling, P B; Jaax, N K

1997-08-01

Ebola virus has been responsible for explosive lethal outbreaks of hemorrhagic fever in both humans and nonhuman primates. Previous studies showed a predilection of Ebola virus for cells of the mononuclear phagocyte system and endothelial cells. To examine the distribution of lesions and Ebola virus antigen in the tissues of six adult male African green monkeys (Cercopithecus aethiops) that died 6 to 7 days after intraperitoneal inoculation of Ebola-Zaire (Mayinga) virus. Tissues were examined histologically, immunohistochemically, and ultrastructurally. A major novel finding of this study was that fibroblastic reticular cells were immunohistochemically and ultrastructurally identified as targets of Ebola virus infection. The role of Ebola virus-infected fibroblastic reticular cells in the pathogenesis of Ebola hemorrhagic fever warrants further investigation. This is especially important because of recent observations indicating that fibroblastic reticular cells, along with the reticular fibers they produce, maximize the efficiency of the immune response.

Quantitative assessment of synovial inflammation by dynamic gadolinium-enhanced magnetic resonance imaging. A study of the effect of intra-articular methylprednisolone on the rate of early synovial enhancement

DEFF Research Database (Denmark)

Østergaard, Mikkel; Stoltenberg, M; Henriksen, O

1996-01-01

The effect of temporary inflammatory suppression on synovial membrane enhancement, as determined by dynamic and static gadolinium-DTPA enhanced magnetic resonance imaging (MRI), was studied. MRI of 18 arthritic knees was performed before and 1, 7, 30 and 180 days after intra-articular methylpredn......The effect of temporary inflammatory suppression on synovial membrane enhancement, as determined by dynamic and static gadolinium-DTPA enhanced magnetic resonance imaging (MRI), was studied. MRI of 18 arthritic knees was performed before and 1, 7, 30 and 180 days after intra...

Synovial cysts of the hip joint and iliopsoas bursitis: A spectrum of imaging abnormalities

International Nuclear Information System (INIS)

Sartoris, D.J.; Resnick, D.; Greenway, G.

1985-01-01

Synovium-related soft tissue disease around the hip constitutes a spectrum ranging from isolated iliopsoas bursitis to pure articular synovial herniations without bursal involvement. The clinical, pathologic, and radiographic features of these entities are discussed as they pertain to the variety of underlying disorder which predispose to their occurrence. Nine case reports are utilized to illustrate the variable clinical and radiographic presentations which may be encountered. Based upon these cases as well as those in the literature, an imaging algorithm has been developed which should eliminate unnecessary studies and allow prompt and accurate diagnosis. (orig.)

Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease

Science.gov (United States)

Gourdie, Robert G.; Dimmeler, Stefanie; Kohl, Peter

2016-01-01

Our understanding of cardiac fibroblast functions has moved beyond their roles in heart structure and extracellular matrix generation, and now includes contributions to paracrine, mechanical and electrical signalling during ontogenesis and normal cardiac activity. Fibroblasts have central roles in pathogenic remodelling during myocardial ischaemia, hypertension and heart failure. As key contributors to scar formation, they are crucial for tissue repair after interventions including surgery and ablation. Novel experimental approaches targeting cardiac fibroblasts are promising potential therapies for heart disease. Indeed, several existing drugs act, at least partially, through effects on cardiac connective tissue. This Review outlines the origins and roles of fibroblasts in cardiac development, homeostasis and disease; illustrates the involvement of fibroblasts in current and emerging clinical interventions; and identifies future targets for research and development. PMID:27339799

[Analysis of factors related to the number of mesenchymal stem cells derived from synovial fluid of the temporomandibular joint].

Science.gov (United States)

Sun, Y P; Zheng, Y H; Zhang, Z G

2017-06-09

Objective: To analyze related factors on the number of mesenchymal stem cells in the synovial fluid of the temporomandibular joint (TMJ) and provide an research basis for understanding of the source and biological role of mesenchymal stem cells derived from synovial fluid in TMJ. Methods: One hundred and twenty-two synovial fluid samples from 91 temporomandibular disorders (TMD) patients who visited in Department of TMJ Center, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University from March 2013 to December 2013 were collected in this study, and 6 TMJ synovial fluid samples from 6 normal volunteers who were studying in the North Campus of Sun Yat-sen University were also collected, so did their clinical information. Then the relation between the number of mesenchymal stem cells derived from synovial fluid and the health status of the joints, age of donor, disc perforation, condylar bony destruction, blood containing and visual analogue scale score of pain were investigated using Mann-Whitney U test and Spearman rank correlation test. Results: The number of mesenchymal stem cells derived from synovial fluid had no significant relation with visual analogue scale score of pain ( r= 0.041, P= 0.672), blood containing ( P= 0.063), condylar bony destruction ( P= 0.371). Linear correlation between the number of mesenchymal stem cells derived from synovial fluid and age of donor was very week ( r= 0.186, P= 0.043). The number of mesenchymal stem cells up-regulated when the joint was in a disease state ( P= 0.001). The disc perforation group had more mesenchymal stem cells in synovial fluid than without disc perforation group ( P= 0.042). Conclusions: The number of mesenchymal stem cells derived from synovial fluid in TMJ has no correlation with peripheral blood circulation and condylar bony destruction, while has close relation with soft tissue structure damage of the joint.

Synovial fluid multiplex PCR is superior to culture for detection of low-virulent pathogens causing periprosthetic joint infection.

Science.gov (United States)

Morgenstern, Christian; Cabric, Sabrina; Perka, Carsten; Trampuz, Andrej; Renz, Nora

2018-02-01

Analysis of joint aspirate is the standard preoperative investigation for diagnosis of periprosthetic joint infection (PJI). We compared the diagnostic performance of culture and multiplex polymerase chain reaction (PCR) of synovial fluid for diagnosis of PJI. Patients in whom aspiration of the prosthetic hip or knee joint was performed before revision arthroplasty were prospectively included. The performance of synovial fluid culture and multiplex PCR was compared by McNemar's chi-squared test. A total of 142 patients were included, 82 with knee and 60 with hip prosthesis. PJI was diagnosed in 77 patients (54%) and aseptic failure in 65 patients (46%). The sensitivity of synovial fluid culture and PCR was 52% and 60%, respectively, showing concordant results in 116 patients (82%). In patients with PJI, PCR missed 6 high-virulent pathogens (S. aureus, streptococci, E. faecalis, E. coli) which grew in synovial fluid culture, whereas synovial fluid culture missed 12 pathogens detected by multiplex PCR, predominantly low-virulent pathogens (Cutibacterium acnes and coagulase-negative staphylococci). In patients with aseptic failure, PCR detected 6 low-virulent organisms (predominantly C. acnes). While the overall performance of synovial fluid PCR was comparable to culture, PCR was superior for detection of low-virulent bacteria such as Cutibacterium spp. and coagulase-negative staphylococci. In addition, synovial fluid culture required several days for growth, whereas multiplex PCR provided results within 5hours in an automated manner. Copyright © 2017 Elsevier Inc. All rights reserved.

Pannus invasion and cartilage degradation in rheumatoid arthritis: involvement of MMP-3 and interleukin-1beta.

Science.gov (United States)

Ainola, M M; Mandelin, J A; Liljeström, M P; Li, T F; Hukkanen, M V J; Konttinen, Y T

2005-01-01

Synovial inflammation in rheumatoid arthritis (RA) leads to pannus tissue invasion and destruction of cartilage/bone matrix by proteinases. Our intention was to analyze some of the key matrix metalloproteinases (MMPs) in pannus tissue overlying evolving cartilage erosions in RA. Frozen tissue samples of pannus and synovium from advanced RA and synovium from osteoarthritic patients were used for immunohistochemical, western blotting and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis of MMP-1, -3, -13 and -14. Synovial fibroblast cultures, stimulated with tumour necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), were analyzed with enzyme-linked immunosorbent assays (ELISA) and quantitative RT-PCR. MMP-3 was highly expressed in pannus tissue compared with significantly lower expression levels of MMP-1, -13 and -14. In fibroblast cultures IL-1beta was a potent stimulus for MMP-3, whereas TNF-alpha was more potent for MMP-1. This is the first study to demonstrate quantitatively in real time that MMP-3 mRNA expression is clearly higher in advanced RA pannus tissue compared to parallel RA or osteoarthritic synovium. MMP-3 mRNA levels were also clearly overexpressed in RA pannus compared to MMP-1, -13 and -14. Advanced RA has previously been found to overexpress IL-1beta. The high expression of MMP-3 in pannus and IL-1beta, mediated stimulation of MMP-3 suggest that MMP-3 plays a significant role in the progression of erosions through the proteoglycan-rich cartilage matrix.

Anterior mediastinal synovial sarcoma: A case report and literature review

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Wen-xiang YUE

2015-01-01

Full Text Available Objective　To study the clinical manifestations, pathologic features, diagnosis, treatment and prognosis of primary synovial sarcoma in the anterior mediastinum. Methods　A case of primary synovial sarcoma in the anterior mediastinum was reported. Clinical features, imaging manifestations, pathology features and therapeutic effect were analysed and the relevant literature was reviewed. Results　A 48-year-male patient was admitted with complaint of right chest pain for 4 days. Chest computerized tomography revealed a large mass located at the right anterior mediastinum, and it was primarily diagnosed as invasive thymoma. Pathological examination by CT-guided percutaneous needle biopsy manifested that, under microscope, the tumor cells were short and spindle in shape forming a nest structure, suggested it was a thymoma. The patient then underwent resection of thymoma with removal of fat and connective tissue in the anterior mediastinum. During the operation the size of the tumor was 15cm×15cm×10cm, being located at the anterior mediastinum, and it tended to bleed. The diagnosis of primary monophasic synovial sarcoma in the mediastinum was confirmed by postoperative/pathology examination. Immunohistochemistry staining showed that the tumor cells were positive for the markers Bcl-2 and EMA, but negative for the markers CK (pan and S100. The patient suffered from local recurrence with metastases to lung 4 months after surgery. The patient received 2 chemotherapeutic courses with ifosfamide, epirubicin and cisplatin. He died 6 months after surgery. Conclusion　Primary synovial sarcoma in the anterior mediastinum is an extremely rare and highly malignant tumor with poor prognosis. The diagnosis depends on the pathological features, immunohistochemistry and RT-PCR. Radical resection combined with comprehensive treatment may improve the survival rate. DOI: 10.11855/j.issn.0577-7402.2014.12.12

Fibroblast-matrix interplay: Nintedanib and pirfenidone modulate the effect of IPF fibroblast-conditioned matrix on normal fibroblast phenotype.

Science.gov (United States)

Epstein Shochet, Gali; Wollin, Lutz; Shitrit, David

2018-03-12

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. Activated fibroblasts are the key effector cells in fibrosis, producing excessive amounts of collagen and extracellular matrix (ECM) proteins. Whether the ECM conditioned by IPF fibroblasts determines the phenotype of naïve fibroblasts is difficult to explore. IPF-derived primary fibroblasts were cultured on Matrigel and then cleared using ammonium hydroxide, creating an IPF-conditioned matrix (CM). Normal fibroblast CM served as control. Normal fibroblasts were cultured on both types of CM, and cell count, cell distribution and markers of myofibroblast differentiation; transforming growth factor beta (TGFβ) signalling; and ECM expression were assessed. The effects of the anti-fibrotic drugs nintedanib and pirfenidone at physiologically relevant concentrations were also explored. Normal fibroblasts cultured on IPF-CM arranged in large aggregates as a result of increased proliferation and migration. Moreover, increased levels of pSmad3, pSTAT3 (phospho signal transducer and activator of transcription 3), alpha smooth muscle actin (αSMA) and Collagen1a were found, suggesting a differentiation towards a myofibroblast-like phenotype. SB505124 (10 μmol/L) partially reversed these alterations, suggesting a TGFβ contribution. Furthermore, nintedanib at 100 nmol/L and, to a lesser extent, pirfenidone at 100 μmol/L prevented the IPF-CM-induced fibroblast phenotype alterations, suggesting an attenuation of the ECM-fibroblast interplay. IPF fibroblasts alter the ECM, thus creating a CM that further propagates an IPF-like phenotype in normal fibroblasts. This assay demonstrated differences in drug activities for approved IPF drugs at clinically relevant concentrations. Thus, the matrix-fibroblast phenotype interplay might be a relevant assay to explore drug candidates for IPF treatment. © 2018 Asian Pacific Society of Respirology.

Monophasic Synovial Sarcoma of Prostatic Fascia: Case Report and Literature Review

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Lucio Olivetti

2015-01-01

Full Text Available Synovial sarcoma (SS primarily occurs in the para-articular soft tissue of the lower extremities in young adults and it is extremely rare in the prostatic region. We report a case of a 46-year-old man who presented with urinary retention. Pelvic ultrasound (US examination, computed tomography (CT, and magnetic resonance imaging (MRI demonstrated an 8.5 cm mass that appeared to originate in the prostatic fascia of the right lobe. Preoperative prostatic ultrasound transrectal needle biopsy revealed mesenchymal neoplastic tissue. Patient underwent surgery. The final pathologic findings were consistent with the diagnosis of monophasic synovial sarcoma.

Monophasic Synovial Sarcoma of Prostatic Fascia: Case Report and Literature Review.

Science.gov (United States)

Olivetti, Lucio; Benecchi, Luigi; Corti, Serena; Del Boca, Carlo; Ferrari, Matteo; Sergio, Pietro; Bercich, Luisa; Tanzi, Giulia

2015-01-01

Synovial sarcoma (SS) primarily occurs in the para-articular soft tissue of the lower extremities in young adults and it is extremely rare in the prostatic region. We report a case of a 46-year-old man who presented with urinary retention. Pelvic ultrasound (US) examination, computed tomography (CT), and magnetic resonance imaging (MRI) demonstrated an 8.5 cm mass that appeared to originate in the prostatic fascia of the right lobe. Preoperative prostatic ultrasound transrectal needle biopsy revealed mesenchymal neoplastic tissue. Patient underwent surgery. The final pathologic findings were consistent with the diagnosis of monophasic synovial sarcoma.

KNEE CARTILAGE AND SYNOVIAL MEMBRANE STRUCTURAL CHANGES DURING TIBIA DISTRACTION WITH PLATING

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T. A. Stupina

2017-01-01

Full Text Available Purpose of the study — to analyze the changes in knee articular cartilage and synovial membrane during distraction external fixation of the tibia in combination with plating.Material and methods. Articular cartilage and synovial membrane of the knee joint were studied using histomorphometry methods in 9 mongrel dogs during distraction external fixation of the tibia combined with plating. Tibia and fibula osteotomies were performed at the border of middle and upper third, plate was fixed on tibia diaphysis. Lengthening was achieved at rate of 1 mm per day in four stages during 21–28 days. Animals were withdrawn from experiment in 30 and 90 days. After autopsy of knee joints the authors excised sections of synovial membrane from suprapatellar area, articular cartilage with underlying subchondral bone from loadable surface of femoral condyles. Thickness of articular cartilage, its area and volumetric density of chondrocytes was measured, proportion of chondrocytes within isogenic groups from the overall number of chondrocytes as well as proportion of empty lacunae. In synovial membrane the authors measured thickness of surface layer and numeric density of micro vessels. Articular cartilage of 5 intact animals was used as a control group.Results. After 30 days of plate fixation a hyperplasia of the integument layer, mild synovitis, and hypervascularization were observed in synovial membrane. Density of micro vessels increased to 363.93±33.71 (control group — 335.05±28.88. The authors also observed subperineural and endoneural edema as well as destruction of nerve fibers in subsynovial layer. Articular cartilage retained the zonal structure. Destructive changes were manifested by fibers separation in the superficial part of surface zone and by partial loss of chondrocytes. The following parameters were reduced: cartilage thickness, area and volumetric density of chondrocytes, proportion of isogenic groups; empty lacunae exceeded the values in

Symptomatic intraspinal synovial cysts: Opacification and treatment by percutaneous injection

International Nuclear Information System (INIS)

Bjorkengren, A.G.; Resnick, D.; Kurz, L.T.; Garfin, S.R.; Sartoris, D.J.

1986-01-01

Synovial cysts in an intraspinal location, associated with facet joint osteoarthritis, have been diagnosed using CT. Surgical removal of the cyst, when believed to be the cause of radiculopathy, has resulted in symptomatic relief. The authors have applied a nonoperative treatment method consisting of CT-guided needle placement in the facet joint adjacent to the cyst, followed by injection of contrast material and corticosteroids. Three patients were treated without complications and with complete relief of symptoms in two cases and partial relief in one, although no decrease in the size of the cysts was demonstrated on follow-up CT scans. The preliminary results indicate a possible role for this treatment technique in patients with intraspinal synovial cysts

Effect of intraarticular osmic acid on synovial membrane volume and inflammation, determined by magnetic resonance imaging

DEFF Research Database (Denmark)

Østergaard, Mikkel; Stoltenberg, M; Gideon, P

1995-01-01

The changes in MR-determined synovial membrane volume, early synovial enhancement, and cartilage and bone erosions after osmic acid knee synovectomy were studied. Gadolinium-DTPA enhanced magnetic resonance imaging (MRI) of 18 knees with persistent arthritis was performed before and 1 month after...

Cervical Synovial Sarcoma In a Young Boy

African Journals Online (AJOL)

Synovial sarcomas comprise about 8% of all tumours of somatic soft-tissues, and are the most common sar- comas of the 'hands and feet. Occasionally they may occur in the trunk, but they have rarely been reported in the neck. We present a case of cervical soft-tissue mass pro- ducing symptoms in a 12-year-old-boy.

Response to pazopanib in two pediatric patients with pretreated relapsing synovial sarcoma.

Science.gov (United States)

Casanova, Michela; Basso, Eleonora; Magni, Chiara; Bergamaschi, Luca; Chiaravalli, Stefano; Carta, Roberto; Tirtei, Elisa; Massimino, Maura; Fagioli, Franca; Ferrari, Andrea

2017-01-21

Pazopanib is an oral multikinase inhibitor that has proved effective in adults treated for relapsing soft tissue sarcoma and synovial sarcoma in particular. Two cases are reported here of pediatric patients with pretreated relapsing synovial sarcoma whose tumors showed a prolonged response to pazopanib given on compassionate grounds. These results suggest that new agents found effective in adult patients might achieve similar results in adolescents with the same disease. Facilitating the availability of new drugs for children and adolescents is a major challenge for pediatric oncologists.

Synovial chondromatosis of the shoulder: imaging findings; Osteocondromatose sinovial no ombro: achados por metodos de imagem

Energy Technology Data Exchange (ETDEWEB)

Terazaki, Carlos Renato Ticianelli; Trippia, Carlos Henrique; Caboclo, Maria Fernanda Sales Ferreira; Medaglia, Carla Regina Miranda, E-mail: reticianelli@hotmail.com [Hospital Sao Vicente (FUNEF), Curitiba, PR (Brazil). Servico de Radiologia e Diagnostico por Imagem; Trippia, Cesar Rodrigo [Hospital Sao Vicente (FUNEF), Curitiba, PR (Brazil)

2014-01-15

Synovial chondromatosis is a benign condition characterized by synovial proliferation and metaplasia, with development of cartilaginous or osteocartilaginous nodules within a joint, bursa or tendon sheath. In the shoulder, synovial osteochondromatosis may occur within the glenohumeral joint and its recesses (including the tendon sheath of the biceps long head), and in the subacromial-deltoid bursa. Such condition can be identified either by radiography, ultrasonography or magnetic resonance imaging, showing typical features according to each method. Radiography commonly shows ring-shaped calcified cartilages and periarticular soft tissues swelling with erosion of joint margins. Ultrasonography demonstrates hypoechogenic cartilaginous nodules with progressive increase in echogenicity as they become calcified, with development of posterior acoustic shadow in case of ossification. Besides identifying cartilaginous nodules, magnetic resonance imaging can also demonstrate the degree of synovial proliferation. The present study is aimed at describing the imaging findings of this entity in the shoulder. (author)

What drives osteoarthritis?-synovial versus subchondral bone pathology.

Science.gov (United States)

Hügle, Thomas; Geurts, Jeroen

2017-09-01

Subchondral bone and the synovium play an important role in the initiation and progression of OA. MRI often permits an early detection of synovial hypertrophy and bone marrow lesions, both of which can precede cartilage damage. Newer imaging modalities including CT osteoabsorptiometry and hybrid SPECT-CT have underlined the importance of bone in OA pathogenesis. The subchondral bone in OA undergoes an uncoupled remodelling process, which is notably characterized by macrophage infiltration and osteoclast formation. Concomitant increased osteoblast activity leads to spatial remineralization and osteosclerosis in end-stage disease. A plethora of metabolic and mechanical factors can lead to synovitis in OA. Synovial tissue is highly vascularized and thus exposed to systemic influences such as hypercholesterolaemia or low grade inflammation. This review aims to describe the current understanding of synovitis and subchondral bone pathology and their connection in OA. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A role for the high-density lipoprotein receptor SR-B1 in synovial inflammation via serum amyloid-A.

LENUS (Irish Health Repository)

Mullan, Ronan Hugh

2012-02-01

Acute phase apoprotein Serum Amyloid A (A-SAA), which is strongly expressed in rheumatoid arthritis synovial membrane (RA SM), induces angiogenesis, adhesion molecule expression, and matrix metalloproteinase production through the G-coupled receptor FPRL-1. Here we report alternative signaling through the high-density lipoprotein receptor scavenger receptor-class B type 1 (SR-B1). Quantitative expression\\/localization of SR-B1 in RA SM, RA fibroblast-like cells (FLCs), and microvascular endothelial cells (ECs) was assessed by Western blotting and immunohistology\\/fluorescence. A-SAA-mediated effects were examined using a specific antibody against SR-B1 or amphipathic alpha-Helical Peptides (the SR-B1 antagonists L-37pA and D-37pA), in RA FLCs and ECs. Adhesion molecule expression and cytokine production were quantified using flow cytometry and ELISA. SR-B1 was strongly expressed in the RA SM lining layer and endothelial\\/perivascular regions compared with osteoarthritis SM or normal control synovium. Differential SR-B1 expression in RA FLC lines (n = 5) and ECs correlated closely with A-SAA, but not tumor necrosis factor alpha-induced intercellular adhesion molecule-1 upregulation. A-SAA-induced interleukin-6 and -8 production was inhibited in the presence of anti-SR-B1 in human microvascular endothelial cells and RA FLCs. Moreover, D-37pA and L-37pA inhibited A-SAA-induced vascular cell adhesion molecule-1 and intercellular adhesion molecule expression from ECs in a dose-dependent manner. As SR-B1 is expressed in RA synovial tissue and mediates A-SAA-induced pro-inflammatory pathways, a better understanding of A-SAA-mediated inflammatory pathways may lead to novel treatment strategies for RA.

Innovative Surgical Management of the Synovial Chondromatosis of Temporo-Mandibular Joints: Highly Conservative Surgical Technique.

Science.gov (United States)

Ionna, Franco; Amantea, Massimiliano; Mastrangelo, Filiberto; Ballini, Andrea; Maglione, Maria Grazia; Aversa, Corrado; De Cecio, Rossella; Russo, Daniela; Marrelli, Massimo; Tatullo, Marco

2016-07-01

Synovial chondromatosis (SC) is an uncommon disease characterized by a benign nodular cartilaginous proliferation arising from the joint synovium, bursae, or tendon sheaths. Although the temporomandibular joint is rarely affected by neoplastic lesions, SC is the most common neoplastic lesion of this joint. The treatment of this disease consists in the extraoral surgery with a wide removal of the lesion; in this study, the authors described a more conservative intraoral surgical approach. Patient with SC of temporomandibular joint typically refer a limitation in the mouth opening, together with a persistent not physiological mandibular protrusion and an appearance of a neoformation located at the right preauricular region: the authors reported 1 scholar patient. After biopsy of the neoformation, confirming the synovial chondromatosis, the patient underwent thus to the surgical excision of the tumor, via authors' conservative transoral approach, to facilitate the enucleation of the neoformation. The mass fully involved the pterygo-maxillary fossa with involvement of the parotid lodge and of the right TMJ: this multifocal extension suggested for a trans-oral surgical procedure, in the light of the suspicion of a possible malignant nature of the neoplasm. Our intraoral conservative approach to surgery is aimed to reduce the presence of unaesthetic scars in preauricular and facial regions, with surgical results undoubtedly comparable to the traditional surgical techniques much more aggressive. Our technique could be a valid, alternative, and safe approach to treat this rare and complex kind of oncological disease.

Synovial Cyst: A Culprit for Recalcitrant Iliotibial Band Syndrome: A Case Report

Directory of Open Access Journals (Sweden)

Yeoh CSN

2015-11-01

Full Text Available We present the case of a 56-year old gentleman who presented with recalcitrant iliotibial band (ITB friction syndrome which did not improve with various modalities of conservative treatment. Magnetic Resonance Imaging (MRI of the affected knee did not show pathology typical of ITB friction syndrome. However, open exploration revealed a synovial cyst deep to the iliotibial band, abutting against the anterolateral capsule. The presence of distinctive clinical signs on physical examination should alert clinicians to consider knee synovial cyst as a differential diagnosis when dealing with recalcitrant ITB syndrome.

A Challenging Case of Metastatic Intra-Abdominal Synovial Sarcoma with Unusual Immunophenotype and Its Differential Diagnosis

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Yi-Che Changchien

2012-01-01

Full Text Available The primary and metastatic gastrointestinal synovial sarcoma is rare with a wide differential diagnosis. It usually expresses cytokeratins EMA, BCL2 with an occasional CD99, and S100 positivity but not desmin. We present a case of metastatic synovial sarcoma with unusual immunophenotype causing diagnostic challenges. The tumor cells showed focal cytokeratin, EMA, and, unexpectedly, desmin positivity. Additional intranuclear TLE-1 positivity and negativity for CD34 and DOG-1 were also identified. A diagnosis of monophasic synovial sarcoma was confirmed by using FISH break-apart probe. RT-PCR revealed the SYT-SSX1 fusion gene. Intra-abdominal synovial sarcoma, either primary or metastatic, with unusual desmin positivity raises the diagnostic challenge, since a wide range of differential diagnoses could show a similar immunophenotype (leiomyosarcoma, desmoid tumor, myofibroblastic tumor, and rarely GIST etc.. Typical morphology and focal cytokeratin/EMA positivity should alert to this tumor, and FISH and RT-PCR remain the gold standard for the confirmation.

MRI features of three paediatric intra-articular synovial lesions: a comparative study

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Kan, J.H. [Monroe Carell Jr. Children' s Hospital at Vanderbilt, Nashville, TN (United States)], E-mail: herman.kan@vanderbilt.edu; Hernanz-Schulman, M. [Monroe Carell Jr. Children' s Hospital at Vanderbilt, Nashville, TN (United States); Damon, B.M.; Yu, Chang [Vanderbilt University, Nashville, TN (United States); Connolly, S.A. [Boston Children' s Hospital, Boston, IL (United States)

2008-07-15

Aim: To determine reliable magnetic resonance imaging (MRI) features differentiating three paediatric intra-articular congenital or neoplastic synovial lesions that contain blood products, from post-traumatic or haemorrhagic inflammatory processes. Materials and methods: This was a retrospective review of MRI findings of 22 paediatric intra-articular congenital or neoplastic synovial lesions, including venous malformation (VM) (n = 12), pigmented villonodular synovitis (PVNS; n = 8), and synovial sarcoma (SS; n = 2). These MRI features were compared with 22 paediatric post-traumatic or inflammatory intra-articular processes containing blood products and producing mass effect. The following imaging features were assessed: presence of a discrete mass, extension, extra-articular oedema, susceptibility, joint effusion, and size. Fisher's exact test was used and results were considered statistically significant when p < 0.05. Results: The three intra-articular synovial lesions, compared with controls, were more likely to directly invade osseous structures when a discrete mass was present (13/16, 81.3% versus 1/9, 11.1%; p < 0.002) and extend into extra-articular soft tissues (13/21, 61.9% versus 2/17, 11.8%; p < 0.003), but were less likely to show extra-articular oedema (3/22, 13.6% versus 13/22, 59.1%; p < 0.004), a joint effusion (10/22,45.5% versus 19/22, 86.4%, p < 0.01), susceptibility within a joint effusion (0/22, 0% versus 11/22, 40.9%; p = 0.00), osseous oedema (3/16, 18.8% versus 7/9, 77.8%; p < 0.009), and synovial enhancement (8/21, 38.1% versus 14/16, 87.5%; p < 0.003). VMs had characteristic tubular vessels with internal fluid-fluid levels (11/12) that extended into bone (10/12) and extracapsular soft tissues (11/12). Conclusion: Our study indicates that, despite the overlapping presence of haemorrhagic products, intra-articular VM, PVNS, and SS show MRI features that permit distinction from acquired post-traumatic and haemorrhagic inflammatory

Degranulating mast cells in fibrotic regions of human tumors and evidence that mast cell heparin interferes with the growth of tumor cells through a mechanism involving fibroblasts

International Nuclear Information System (INIS)

Samoszuk, Michael; Kanakubo, Emi; Chan, John K

2005-01-01

The purpose of this study was to test the hypothesis that mast cells that are present in fibrotic regions of cancer can suppress the growth of tumor cells through an indirect mechanism involving peri-tumoral fibroblasts. We first immunostained a wide variety of human cancers for the presence of degranulated mast cells. In a subsequent series of controlled in vitro experiments, we then co-cultured UACC-812 human breast cancer cells with normal fibroblasts in the presence or absence of different combinations and doses of mast cell tryptase, mast cell heparin, a lysate of the human mast cell line HMC-1, and fibroblast growth factor-7 (FGF-7), a powerful, heparin-binding growth factor for breast epithelial cells. Degranulating mast cells were localized predominantly in the fibrous tissue of every case of breast cancer, head and neck cancer, lung cancer, ovarian cancer, non-Hodgkin's lymphoma, and Hodgkin's disease that we examined. Mast cell tryptase and HMC-1 lysate had no significant effect on the clonogenic growth of cancer cells co-cultured with fibroblasts. By contrast, mast cell heparin at multiple doses significantly reduced the size and number of colonies of tumor cells co-cultured with fibroblasts, especially in the presence of FGF-7. Neither heparin nor FGF-7, individually or in combination, produced any significant effect on the clonogenic growth of breast cancer cells cultured without fibroblasts. Degranulating mast cells are restricted to peri-tumoral fibrous tissue, and mast cell heparin is a powerful inhibitor of clonogenic growth of tumor cells co-cultured with fibroblasts. These results may help to explain the well-known ability of heparin to inhibit the growth of primary and metastatic tumors

Degranulating mast cells in fibrotic regions of human tumors and evidence that mast cell heparin interferes with the growth of tumor cells through a mechanism involving fibroblasts

Directory of Open Access Journals (Sweden)

Kanakubo Emi

2005-09-01

Full Text Available Abstract Background The purpose of this study was to test the hypothesis that mast cells that are present in fibrotic regions of cancer can suppress the growth of tumor cells through an indirect mechanism involving peri-tumoral fibroblasts. Methods We first immunostained a wide variety of human cancers for the presence of degranulated mast cells. In a subsequent series of controlled in vitro experiments, we then co-cultured UACC-812 human breast cancer cells with normal fibroblasts in the presence or absence of different combinations and doses of mast cell tryptase, mast cell heparin, a lysate of the human mast cell line HMC-1, and fibroblast growth factor-7 (FGF-7, a powerful, heparin-binding growth factor for breast epithelial cells. Results Degranulating mast cells were localized predominantly in the fibrous tissue of every case of breast cancer, head and neck cancer, lung cancer, ovarian cancer, non-Hodgkin's lymphoma, and Hodgkin's disease that we examined. Mast cell tryptase and HMC-1 lysate had no significant effect on the clonogenic growth of cancer cells co-cultured with fibroblasts. By contrast, mast cell heparin at multiple doses significantly reduced the size and number of colonies of tumor cells co-cultured with fibroblasts, especially in the presence of FGF-7. Neither heparin nor FGF-7, individually or in combination, produced any significant effect on the clonogenic growth of breast cancer cells cultured without fibroblasts. Conclusion Degranulating mast cells are restricted to peri-tumoral fibrous tissue, and mast cell heparin is a powerful inhibitor of clonogenic growth of tumor cells co-cultured with fibroblasts. These results may help to explain the well-known ability of heparin to inhibit the growth of primary and metastatic tumors.

The use of native fluorescence analysis of synovial fluid in the diagnosis of medial compartment disease in medium- and large-breed dogs.

Science.gov (United States)

Bilská, Kamila; Šteffeková, Zuzana; Birková, Anna; Mareková, Mária; Ledecký, Valent; Hluchý, Marián; Kisková, Terézia

2016-05-01

We assumed that proteins are most likely responsible for synovial fluid fluorescence and that changes detected in fluorescence intensity are most likely the result of changes in the concentration of fluorescent proteins. Synchronous fluorescent matrices from synovial fluid samples were measured in the excitation wavelength range of 200-350 nm using a luminescence spectrophotometer. The synchronous matrix of synovial fluid consists of 2 dominant fluorescent centers (F1 and F2) in the ultraviolet region. The fluorescence intensities of both centers were significantly higher in pathological samples, with p = 0.001 (a 59% increase of the median value) for the F1 center and p = 0.002 (a 52% increase of the median value) for the F2 center. Receiver operating characteristic analysis confirmed that synovial fluid autofluorescence is a significant predictor of medial compartment disease in dogs, with the area under the curve at 0.776 (F1) and 0.778 (F2). We did not detect any differences in the autofluorescence of synovial fluid between male and female, or any breed-based changes. No position changes of fluorescent centers were recorded in the synovial fluid in diseased dogs compared with healthy dogs. The synovial fluid metabolic fingerprint of canine patients with medial compartment disease differed from that of healthy dogs. Our study demonstrated the feasibility of synovial fluid fingerprinting to identify disease-specific profiles of synovial fluid metabolites. © 2016 The Author(s).

Measurement of glycosaminoglycans in canine synovial fluid and its correlation with the cause of secondary osteoarthritis, age and body weight

Directory of Open Access Journals (Sweden)

Radka Andrysíková

2012-01-01

Full Text Available Glycosaminoglycans are natural components of healthy joint cartilage and they also appear in healthy synovial fluid. An increased amount of glycosaminoglycans in synovial fluid is believed to be a marker of secondary osteoarthritis, regardless of its primary cause. The aim of our study was to define the relationship between glycosaminoglycans in the synovial fluid and joint disorders, age, and body weight. The samples of synovial fluid were obtained from dogs suffering from secondary secondary osteoarthritis (n = 35 and from control dogs (n = 18; control dogs had normal body weight. The results were compared among joints of dogs with secondary osteoarthritis divided into groups according to the criteria mentioned above and control dogs. Glycosaminoglycan concentrations in synovial fluid were measured using dimethylmethylene blue assay. The lowest mean value of glycosaminoglycans in synovial fluid was measured in the control group. Significantly higher glycosaminoglycan content (P < 0.05 was found in synovial fluid isolated from obese dogs compared to control dogs. Furthermore, we observed an age-related trend, in which the highest mean values were reached either in old dogs or pups. Despite the absence of significant differences in glycosaminoglycan values among dogs suffering from various types of secondary secondary osteoarthritis, the highest mean values were measured in fragmented coronoid processus group. Our data suggest that abnormally increased body weight has an impact on glycosaminoglycan concentration in synovial fluid which may imply faster degradation and turnover of joint cartilage. Such observation has not yet been published in veterinary medicine.

Bilateral spontaneous pneumothorax with pulmonary metastases of synovial sarcoma

International Nuclear Information System (INIS)

Matushita, J.P.K.; Azevedo, C.M. de

1989-01-01

The association of bilateral spontaneous pneumothorax with pulmonary tumor is uncommon and with pulmonary metastases is rare. The clinical and radiological features of bilateral spontaneous pneumothorax from a synovial sarcoma in a 14 years old boy are described. (author) [pt

Zymographic analysis using gelatin-coated film of the effect of etanercept on the extracellular matrix-degrading activity in synovial fluids of rheumatoid arthritis patients.

Science.gov (United States)

Kamataki, Akihisa; Ishida, Mutsuko; Komagamine, Masataka; Yoshida, Masaaki; Ando, Takanobu; Sawai, Takashi

2016-04-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Most RA patients develop cartilage and bone destruction, and various proteinases are involved in the destruction of extracellular matrix of cartilage and bone. The aim of this study is to evaluate the utility of our newly developed method to measure total gelatinolytic activity. We adopted this method for measurement in synovial fluid from RA patients treated by the anti-rheumatic drug etanercept (ETN), a recombinant human soluble tumor necrosis factor receptor fusion protein, and compared the findings with clinical and laboratory data. Enzymatic activity of synovial fluid was analyzed by zymography using gelatin-coated film, and compared with the index of Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP), CRP and matrix metalloproteinase (MMP)-3 level before and after ETN therapy. Synovial fluids of 19 patients were collected before and after administration of ETN therapy. In nine of 19 patients, who showed a decrease in gelatin-degrading activity in synovial fluid, the index of DAS28-CRP (4.85-2.85, ΔDAS = -2.00) and CRP (3.30-0.94 mg/dL, ΔCRP = -2.36) was alleviated after ETN therapy, while cases with no change or an increase in gelatin-degrading activity showed a modest improvement in clinical data: DAS28-CRP (4.23-3.38, ΔDAS = -0.85) and CRP (1.70-0.74 mg/dL, ΔCRP = -0.96). Our newly developed method for measurement of gelatin-degrading activity in synovial fluid from RA patients is highly practicable and useful for predicting the effect of ETN therapy. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

CARFMAP: A Curated Pathway Map of Cardiac Fibroblasts.

Directory of Open Access Journals (Sweden)

Hieu T Nim

Full Text Available The adult mammalian heart contains multiple cell types that work in unison under tightly regulated conditions to maintain homeostasis. Cardiac fibroblasts are a significant and unique population of non-muscle cells in the heart that have recently gained substantial interest in the cardiac biology community. To better understand this renaissance cell, it is essential to systematically survey what has been known in the literature about the cellular and molecular processes involved. We have built CARFMAP (http://visionet.erc.monash.edu.au/CARFMAP, an interactive cardiac fibroblast pathway map derived from the biomedical literature using a software-assisted manual data collection approach. CARFMAP is an information-rich interactive tool that enables cardiac biologists to explore the large body of literature in various creative ways. There is surprisingly little overlap between the cardiac fibroblast pathway map, a foreskin fibroblast pathway map, and a whole mouse organism signalling pathway map from the REACTOME database. Among the use cases of CARFMAP is a common task in our cardiac biology laboratory of identifying new genes that are (1 relevant to cardiac literature, and (2 differentially regulated in high-throughput assays. From the expression profiles of mouse cardiac and tail fibroblasts, we employed CARFMAP to characterise cardiac fibroblast pathways. Using CARFMAP in conjunction with transcriptomic data, we generated a stringent list of six genes that would not have been singled out using bioinformatics analyses alone. Experimental validation showed that five genes (Mmp3, Il6, Edn1, Pdgfc and Fgf10 are differentially regulated in the cardiac fibroblast. CARFMAP is a powerful tool for systems analyses of cardiac fibroblasts, facilitating systems-level cardiovascular research.

CARFMAP: A Curated Pathway Map of Cardiac Fibroblasts.

Science.gov (United States)

Nim, Hieu T; Furtado, Milena B; Costa, Mauro W; Kitano, Hiroaki; Rosenthal, Nadia A; Boyd, Sarah E

2015-01-01

The adult mammalian heart contains multiple cell types that work in unison under tightly regulated conditions to maintain homeostasis. Cardiac fibroblasts are a significant and unique population of non-muscle cells in the heart that have recently gained substantial interest in the cardiac biology community. To better understand this renaissance cell, it is essential to systematically survey what has been known in the literature about the cellular and molecular processes involved. We have built CARFMAP (http://visionet.erc.monash.edu.au/CARFMAP), an interactive cardiac fibroblast pathway map derived from the biomedical literature using a software-assisted manual data collection approach. CARFMAP is an information-rich interactive tool that enables cardiac biologists to explore the large body of literature in various creative ways. There is surprisingly little overlap between the cardiac fibroblast pathway map, a foreskin fibroblast pathway map, and a whole mouse organism signalling pathway map from the REACTOME database. Among the use cases of CARFMAP is a common task in our cardiac biology laboratory of identifying new genes that are (1) relevant to cardiac literature, and (2) differentially regulated in high-throughput assays. From the expression profiles of mouse cardiac and tail fibroblasts, we employed CARFMAP to characterise cardiac fibroblast pathways. Using CARFMAP in conjunction with transcriptomic data, we generated a stringent list of six genes that would not have been singled out using bioinformatics analyses alone. Experimental validation showed that five genes (Mmp3, Il6, Edn1, Pdgfc and Fgf10) are differentially regulated in the cardiac fibroblast. CARFMAP is a powerful tool for systems analyses of cardiac fibroblasts, facilitating systems-level cardiovascular research.

Synovial chondromatosis in a lumbar apophyseal joint

Energy Technology Data Exchange (ETDEWEB)

Burrafato, V.; Campanacci, D.A.; Capanna, R. [Department of Orthopedic Oncology, Centro Traumatologico Ortopedico, Florence (Italy); Franchi, A. [Institute of Pathology, University of Florence, Florence (Italy)

1998-07-01

A 31-year-old woman presented with painful swelling in the right paravertebral region that had been present for 2 years. Radiography and CT revealed an area of increased density due to multiple calcifications localized at the fourth lumbar vertebra. Histological examination revealed that the lesion consisted of nodules of hyaline cartilage, with focal areas of calcification, growing within synovial tissue. (orig.) With 5 figs., 11 refs.

Arthroscopic Transplantation of Synovial Stem Cells Improves Clinical Outcomes in Knees With Cartilage Defects.

Science.gov (United States)

Sekiya, Ichiro; Muneta, Takeshi; Horie, Masafumi; Koga, Hideyuki

2015-07-01

Transplantation of mesenchymal stem cells (MSCs) is one possible strategy to achieve articular cartilage repair. We previously reported that synovial MSCs were highly proliferative and able to undergo chondrogenesis. We also found that placing a suspension of synovial MSCs on a cartilage defect for 10 minutes promoted cartilage repair in rabbit and pig models. However, the in vivo efficacy of this approach has not been tested clinically. We asked whether transplantation of synovial MSCs improves (1) MRI features, (2) histologic features, and (3) clinical evaluation scores in patients with cartilage defects in the knee? Patients with a symptomatic single cartilage lesion of the femoral condyle were indicated for inclusion in our study, and between April 2008 and April 2011, 10 patients were enrolled in this study. All patients completed followups of 3 years or more. The average followup period was 52 months (range, 37-80 months). Synovial MSCs were expanded with 10% autologous human serum for 14 days after digestion. For transplantation, the patient was positioned so that the cartilage defect was facing upward, and synovial MSC suspension was placed on the cartilage defect with a syringe under arthroscopic control. The defect with the applied suspension then was held in the upward position for 10 minutes. Five patients underwent concomitant ACL reconstructions, among whom two had meniscus suturing performed simultaneously. For MRI quantification, the cartilage defect was scored from 0 to 5. Second-look arthroscopy was performed for four patients and biopsy specimens were evaluated histologically. Clinical outcome was assessed using the Lysholm score and Tegner Activity Level Scale at final followup. Comparisons of MRI and Lysholm scores before and after treatment for each patient were analyzed using the Wilcoxon signed-rank test. MRI score (median ± 95% CI) was 1.0 ± 0.3 before and 5.0 ± 0.7 after, and increased after treatment in each patient (p = 0.005). Second

Synovial Mesenchymal Stem Cells Promote Meniscus Regeneration Augmented by an Autologous Achilles Tendon Graft in a Rat Partial Meniscus Defect Model

Science.gov (United States)

Ozeki, Nobutake; Muneta, Takeshi; Matsuta, Seiya; Koga, Hideyuki; Nakagawa, Yusuke; Mizuno, Mitsuru; Tsuji, Kunikazu; Mabuchi, Yo; Akazawa, Chihiro; Kobayashi, Eiji; Saito, Tomoyuki; Sekiya, Ichiro

2015-01-01

Although meniscus defects and degeneration are strongly correlated with the later development of osteoarthritis, the promise of regenerative medicine strategies is to prevent and/or delay the disease's progression. Meniscal reconstruction has been shown in animal models with tendon grafting and transplantation of mesenchymal stem cells (MSCs); however, these procedures have not shown the same efficacy in clinical studies. Here, our aim was to investigate the ability of tendon grafts pretreated with exogenous synovial-derived MSCs to prevent cartilage degeneration in a rat partial meniscus defect model. We removed the anterior half of the medial meniscus and grafted autologous Achilles tendons with or without a 10-minute pretreatment of the tendon with synovial MSCs. The meniscus and surrounding cartilage were evaluated at 2, 4, and 8 weeks (n = 5). Tendon grafts increased meniscus size irrespective of synovial MSCs. Histological scores for regenerated menisci were better in the tendon + MSC group than in the other two groups at 4 and 8 weeks. Both macroscopic and histological scores for articular cartilage were significantly better in the tendon + MSC group at 8 weeks. Implanted synovial MSCs survived around the grafted tendon and native meniscus integration site by cell tracking assays with luciferase+, LacZ+, DiI+, and/or GFP+ synovial MSCs and/or GFP+ tendons. Flow cytometric analysis showed that transplanted synovial MSCs retained their MSC properties at 7 days and host synovial tissue also contained cells with MSC characteristics. Synovial MSCs promoted meniscus regeneration augmented by autologous Achilles tendon grafts and prevented cartilage degeneration in rats. Stem Cells 2015;33:1927–1938 PMID:25993981

Primary Renal Synovial Sarcoma: A Rare Case Report

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Taha Numan Yıkılmaz

2016-12-01

Full Text Available Synovial sarcoma (SS is mainly derived from soft tissues. Primary renal SS is a very rare malignancy with around 60 cases reported in the literature. We report a renal mass which was undistinguishable from urothelial carcinoma clinically and pathologically but diagnosed as a primary renal SS at the definitive pathological diagnosis.

Synovial sarcoma with relevant immunocytochemistry and special emphasis on the monophasic fibrous variant

Directory of Open Access Journals (Sweden)

Kottu Radhika

2010-01-01

Full Text Available Background: Monophasic fibrous synovial sarcoma (SS is the most common variant of SS. Only a few cytological studies are available on this entity. Bcl-2 protein expression has been described as a characteristic marker of SS and is useful for its differentiation from other sarcomas. Cytokeratin and CD99 are also used in detecting SS. Aims: To evaluate synovial sarcoma and its variants cytomorphologically. Materials and Methods: During a period of 10 years 7 months, i.e. from January 1998 to July 2008, 12 cytologic specimens diagnosed as synovial sarcoma were reviewed. Ten cases were diagnosed as SS on aspiration alone but two cases required ancillary technique i.e., immunocytochemistry staining with bcl-2 and cytokeratin. The smears were stained with Papanicolaou and May-Grόnwald-Giemsa stains. Results: All cytologic specimens in our study had similar appearance. Most smears were highly cellular and were made up of densely packed tri-dimensional groups and singly scattered round to oval cells. Cellular monomorphism and vascular channels within the cell groups were the remarkable findings. Only one case showed cytologic evidence of epithelial differentiation. Bcl-2, cytokeratin, CD99 positivity was seen on immunohistochemistry staining. Results were categorized according to age, sex and morphologic variants. Conclusions: Although cytomorphologic features of synovial sarcomas are characteristic enough to permit its recognition, clinical correlation is necessary for accurate diagnosis. Monophasic variant is the most common entity observed in the present study.

Dynamic gadolinium-enhanced magnetic resonance imaging allows accurate assessment of the synovial inflammatory activity in rheumatoid arthritis knee joints: a comparison with synovial histology

DEFF Research Database (Denmark)

Axelsen, Mette Bjørndal; Stoltenberg, M.; Poggenborg, R.

2012-01-01

, the average grade of histological synovial inflammation was determined from four biopsies obtained during surgery. A preoperative series of T(1)-weighted dynamic fast low-angle shot (FLASH) MR images was obtained. Parameters characterizing contrast uptake dynamics, including the initial rate of enhancement...... capsule of the knee joint (Precise ROI). Intra- and interreader agreement was assessed using the intra-class correlation coefficient (ICC). Results: The IRE from the Quick ROI and the Precise ROI revealed high correlations to the grade of histological inflammation (Spearman's correlation coefficient (rho......) = 0.70, p = 0.001 and rho = 0.74, p = 0.001, respectively). Intraand inter-reader ICCs were very high (0.93-1.00). No Whole slice parameters were correlated to histology. Conclusion: DCE-MRI provides fast and accurate assessment of synovial inflammation in RA patients. Manual outlining of the joint...

Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

Energy Technology Data Exchange (ETDEWEB)

Tashiro, Kanae [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Shishido, Mayumi [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Fujimoto, Keiko [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Organelle Homeostasis Research Center, Kyushu University, Fukuoka (Japan); Hirota, Yuko [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Yo, Kazuyuki; Gomi, Takamasa [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Tanaka, Yoshitaka, E-mail: tanakay@bioc.phar.kyushu-u.ac.jp [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Organelle Homeostasis Research Center, Kyushu University, Fukuoka (Japan)

2014-01-03

Highlights: •Autophagosomes accumulate in aged dermal fibroblasts. •Autophagic degradation is impaired in aged dermal fibroblasts. •Autophagy disruption affects extracellular matrix components in dermal fibroblasts. -- Abstract: Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5—genes essential for autophagosome formation—was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility.

Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

International Nuclear Information System (INIS)

Tashiro, Kanae; Shishido, Mayumi; Fujimoto, Keiko; Hirota, Yuko; Yo, Kazuyuki; Gomi, Takamasa; Tanaka, Yoshitaka

2014-01-01

Highlights: •Autophagosomes accumulate in aged dermal fibroblasts. •Autophagic degradation is impaired in aged dermal fibroblasts. •Autophagy disruption affects extracellular matrix components in dermal fibroblasts. -- Abstract: Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5—genes essential for autophagosome formation—was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility

Characterization of the porcine synovial fluid proteome and a comparison to the plasma proteome

DEFF Research Database (Denmark)

Bennike, Tue Bjerg; Barnaby, Omar; Steen, Hanno

2015-01-01

Synovial fluid is present in all joint cavities, and protects the articular cartilage surfaces in large by lubricating the joint, thus reducing friction. Several studies have described changes in the protein composition of synovial fluid in patients with joint disease. However, the protein concen...... data used in the method optimization, human plasma proteomics data, and search results, have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD000935....

Synovial Calprotectin: An Inexpensive Biomarker to Exclude a Chronic Prosthetic Joint Infection.

Science.gov (United States)

Wouthuyzen-Bakker, Marjan; Ploegmakers, Joris J W; Ottink, Karsten; Kampinga, Greetje A; Wagenmakers-Huizenga, Lucie; Jutte, Paul C; Kobold, Anneke C M

2018-04-01

To diagnose or exclude a chronic prosthetic joint infection (PJI) can be a clinical challenge. Therefore, sensitive and specific biomarkers are needed in the diagnostic work-up. Calprotectin is a protein with antimicrobial properties and is released by activated neutrophils, making it a specific marker for infection. Because of its low costs and ability to obtain a quantitative value as a point of care test, it is an attractive marker to use in clinical practice. In addition, the test is already used in routine care in most hospitals for other indications and therefore easy to implement. Between June 2015 and June 2017 we collected synovial fluid of all consecutive patients who underwent revision surgery of a prosthetic joint because of chronic pain with or without prosthetic loosening. Synovial calprotectin was measured using a lateral flow immunoassay. A PJI was defined by the diagnostic criteria described by the Musculoskeletal Infection Society. Fifty-two patients with chronic pain were included. A PJI was diagnosed in 15 of 52 (29%) patients. The median calprotectin in the PJI group was 859 mg/L (interquartile range 86-1707) vs 7 mg/L (interquartile range 3-25) in the control group (P < .001). With a cut-off value of 50 mg/L, synovial calprotectin showed a sensitivity, specificity, positive predictive value, and negative predictive value of 86.7%, 91.7%, 81.3%, and 94.4%, respectively. Synovial calprotectin is a useful and cheap biomarker to use in the diagnostic work-up of patients with chronic pain, especially to exclude a PJI prior to revision surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Synovial cysts of the lumbar spine

International Nuclear Information System (INIS)

Rosa, Ana Claudia Ferreira; Machado, Marcio Martins; Figueiredo, Marco Antonio Junqueira; Cerri, Giovanni Guido

2002-01-01

Intraspinal synovial cysts of the lumbar spine are rare and commonly associated with osteoarthritis of the facet joints, particularly at level L4-L5. Symptoms are uncommon and may include low-back pain or sciatica. These cysts are accurately diagnosed by using computed tomography and magnetic resonance imaging. Diagnosis is essential for the correct management of the cysts. Several treatment options are available including rest and immobilization, computed tomography guided corticosteroid injection, and surgery in patients that are nonresponsive to other treatment methods. (author)

Triple DMARD treatment in early rheumatoid arthritis modulates synovial T cell activation and plasmablast/plasma cell differentiation pathways.

Science.gov (United States)

Walsh, Alice M; Wechalekar, Mihir D; Guo, Yanxia; Yin, Xuefeng; Weedon, Helen; Proudman, Susanna M; Smith, Malcolm D; Nagpal, Sunil

2017-01-01

This study sought to investigate the genome-wide transcriptional effects of a combination of disease modifying anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine and hydroxychloroquine) in synovial tissues obtained from early rheumatoid arthritis (RA) patients. While combination DMARD strategies have been investigated for clinical efficacy, very little data exists on the potential molecular mechanism of action. We hypothesized that tDMARD would impact multiple biological pathways, but the specific pathways were unknown. Paired synovial biopsy samples from early RA patients before and after 6 months of tDMARD therapy were collected by arthroscopy (n = 19). These biopsies as well as those from subjects with normal synovium (n = 28) were profiled by total RNA sequencing. Large differences in gene expression between RA and control biopsies (over 5000 genes) were identified. Despite clinical efficacy, the expression of a restricted set of less than 300 genes was reversed after 6 months of treatment. Many genes remained elevated, even in patients who achieved low disease activity. Interestingly, tDMARD downregulated genes included those involved in T cell activation and signaling and plasmablast/plasma cell differentiation and function. We have identified transcriptomic signatures that characterize synovial tissue from RA patients with early disease. Analysis after 6 months of tDMARD treatment highlight consistent alterations in expression of genes related to T cell activation and plasmablast/plasma cell differentiation. These results provide novel insight into the biology of early RA and the mechanism of tDMARD action and may help identify novel drug targets to improve rates of treatment-induced disease remission.

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

Energy Technology Data Exchange (ETDEWEB)

Zhu, Zhong Xin [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Sun, Cong Cong [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zheng, Jia Yong [Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Zhou, Xuan [Ningbo First Hospital, Ningbo, Zhejiang (China); Cong, Wei Tao [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Xiao Kun, E-mail: proflxk@163.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Jin, Li Tai, E-mail: jin_litai@126.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

2017-06-15

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

International Nuclear Information System (INIS)

Zhu, Zhong Xin; Sun, Cong Cong; Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui; Zheng, Jia Yong; Zhou, Xuan; Cong, Wei Tao; Li, Xiao Kun; Jin, Li Tai

2017-01-01

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

Ablation of synovial pannus using microbubble-mediated ultrasonic cavitation in antigen-induced arthritis in rabbits.

Science.gov (United States)

Qiu, Li; Jiang, Yong; Zhang, Lingyan; Wang, Lei; Luo, Yan

2012-12-01

To investigate the ablative effectiveness of microbubble-mediated ultrasonic cavitation for treating synovial pannus and to determine a potential mechanism using the antigen-induced arthritis model (AIA). Ultrasonic ablation was performed on the knee joints of AIA rabbits using optimal ultrasonic ablative parameters. Rabbits with antigen-induced arthritis were randomly assigned to 4 groups: (1) the ultrasound (US) + microbubble group; (2) the US only group; (3) the microbubble only group, and (4) the control group. At 1 h and 14 days after the first ablation, contrast-enhanced ultrasonography (CEUS) monitoring and pathology synovitis score were used to evaluate the therapeutic effects. Synovial necrosis and microvascular changes were also measured. After the ablation treatment, the thickness of synovium and parameters of time intensity curve including derived peak intensity and area under curve were measured using CEUS, and the pathology synovitis score in the ultrasound + microbubble group was significantly lower than that found in the remaining groups. No damage was observed in the surrounding normal tissues. The mechanism underlying the ultrasonic ablation was related to microthrombosis and microvascular rupture that resulted in synovial necrosis. The results suggest that microbubble-mediated ultrasonic cavitation should be applied as a non-invasive strategy for the treatment of synovial pannus in arthritis under optimal conditions.

On the matter of synovial fluid lubrication: implications for Metal-on-Metal hip tribology.

Science.gov (United States)

Myant, Connor; Cann, Philippa

2014-06-01

Artificial articular joints present an interesting, and difficult, tribological problem. These bearing contacts undergo complex transient loading and multi axes kinematic cycles, over extremely long periods of time (>10 years). Despite extensive research, wear of the bearing surfaces, particularly metal-metal hips, remains a major problem. Comparatively little is known about the prevailing lubrication mechanism in artificial joints which is a serious gap in our knowledge as this determines film formation and hence wear. In this paper we review the accepted lubrication models for artificial hips and present a new concept to explain film formation with synovial fluid. This model, recently proposed by the authors, suggests that interfacial film formation is determined by rheological changes local to the contact and is driven by aggregation of synovial fluid proteins. The implications of this new mechanism for the tribological performance of new implant designs and the effect of patient synovial fluid properties are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Quantification of synovistis by MRI: correlation between dynamic and static gadolinium-enhanced magnetic resonance imaging and microscopic and macroscopic signs of synovial inflammation

DEFF Research Database (Denmark)

Østergaard, Mikkel; Stoltenberg, M; Løvgreen-Nielsen, P

1998-01-01

injection, as the highest correlation coefficients to histologic inflammation were observed in this interval. Dynamic MRI can be used to determine synovial inflammation. Evaluation of large synovial areas one-half to one minute after Gd injection best reflects joint inflammation....... as at the four biopsy sites, and compared to synovial pathology. The rate of early enhancement of the total synovial membrane of the preselected slice, determined by dynamic MRI, was highly correlated with microscopic evidence of active inflammation (Spearman p = 0.73; p ... knees with and without synovial inflammation with a high predictive value (0.81-0.90). Moderate and severe inflammation could not be differentiated. The early enhancement rate was correlated with histologic features of active inflammation, particularly vessel proliferation and mononuclear leucocyte...

Magnetic resonance imaging-determined synovial membrane and joint effusion volumes in rheumatoid arthritis and osteoarthritis: comparison with the macroscopic and microscopic appearance of the synovium

DEFF Research Database (Denmark)

Østergaard, Mikkel; Stoltenberg, M; Løvgreen-Nielsen, P

1997-01-01

OBJECTIVE: To evaluate the relationship between synovial membrane and joint effusion volumes determined by magnetic resonance imaging (MRI) and macroscopic and microscopic synovial pathologic findings in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial biopsies...... were performed, and macroscopic grades of synovitis assigned, at preselected knee sites during arthroscopy or arthrotomy in 17 knees with RA and 25 with OA. Synovial inflammation and 9 separate tissue characteristics were graded histologically. Synovial membrane and joint effusion volumes were...... membrane and effusion volumes may be sensitive markers and/or predictors of disease activity and treatment outcome in RA....

Biochemical Analysis of Synovial Fluid, Cerebrospinal Fluid and Vitreous Humor at Early Postmortem Intervals in Donkeys

Directory of Open Access Journals (Sweden)

Doha Yahia

2014-01-01

Full Text Available Biochemical analysis of body fluids after death is a helpful tool in veterinary forensic medicine. Synovial fluid, cerebrospinal fluid (CSF and vitreous humor are easily accessible and well preserved from contamination. Five donkeys (Equus africanus asinus aged 1 - 2 years old were subjected to the study. Samples (Synovial fluid, CSF and vitreous humor were collected before death (antimortem and then at 2, 4, 6, 8, 10 and 12 hours postmortem. Samples were analyzed for glucose, chloride, sodium, magnesium, potassium, enzymes and total protein. Synovial fluid analysis showed that glucose concentration started to decrease at 6 hours postmortem, while magnesium level increased with time. Other parameters were more stable. CSF analysis showed several changes related to time after death as the decrease in glucose and sodium levels, and the increased levels of potassium, magnesium, calcium and total protein. Vitreous analysis revealed a reduction in glucose level and increased potassium and magnesium concentrations. The present study concluded that biochemical analysis of synovial fluid, vitreous humor and CSF can help in determination of time since death in donkeys. This study recommend using CSF for determination of early post-mortem intervals.

Research Paper: The Impact of Synovial NF-ĸB Activation on Apoptosis Pattern Change During Adjuvant-induced Inflammation

Directory of Open Access Journals (Sweden)

Sahar Golabi

2017-05-01

Conclusion: It seems that apoptosis pattern change plays an important role in the progression and modulation of CFA-induced inflammation and its related symptoms. Also, it can be concluded that synovial NF-ĸB had a crucial role in synovial apoptosis change during the study period.

PPAR-δ Agonist With Mesenchymal Stem Cells Induces Type II Collagen-Producing Chondrocytes in Human Arthritic Synovial Fluid.

Science.gov (United States)

Heck, Bruce E; Park, Joshua J; Makani, Vishruti; Kim, Eun-Cheol; Kim, Dong Hyun

2017-08-01

Osteoarthritis (OA) is an inflammatory joint disease characterized by degeneration of articular cartilage within synovial joints. An estimated 27 million Americans suffer from OA, and the population is expected to reach 67 million in the United States by 2030. Thus, it is urgent to find an effective treatment for OA. Traditional OA treatments have no disease-modifying effect, while regenerative OA therapies such as autologous chondrocyte implantation show some promise. Nonetheless, current regenerative therapies do not overcome synovial inflammation that suppresses the differentiation of mesenchymal stem cells (MSCs) to chondrocytes and the expression of type II collagen, the major constituent of functional cartilage. We discovered a synergistic combination that overcame synovial inflammation to form type II collagen-producing chondrocytes. The combination consists of peroxisome proliferator-activated receptor (PPAR) δ agonist, human bone marrow (hBM)-derived MSCs, and hyaluronic acid (HA) gel. Interestingly, those individual components showed their own strong enhancing effects on chondrogenesis. GW0742, a PPAR-δ agonist, greatly enhanced MSC chondrogenesis and the expression of type II collagen and glycosaminoglycan (GAG) in hBM-MSC-derived chondrocytes. GW0742 also increased the expression of transforming growth factor β that enhances chondrogenesis and suppresses cartilage fibrillation, ossification, and inflammation. HA gel also increased MSC chondrogenesis and GAG production. However, neither GW0742 nor HA gel could enhance the formation of type II collagen-producing chondrocytes from hBM-MSCs within human OA synovial fluid. Our data demonstrated that the combination of hBM-MSCs, PPAR-δ agonist, and HA gel significantly enhanced the formation of type II collagen-producing chondrocytes within OA synovial fluid from 3 different donors. In other words, the novel combination of PPAR-δ agonist, hBM-MSCs, and HA gel can overcome synovial inflammation to form

Oxidative damage in synovial tissue is associated with in vivo hypoxic status in the arthritic joint.

LENUS (Irish Health Repository)

Biniecka, Monika

2012-02-01

OBJECTIVES: To assess levels of oxidative DNA damage (8-oxo-7,8-dihydro-2\\'-deoxyguanine; 8-oxo-dG) and lipid peroxidation (4-hydroxy-2-nonenal; 4-HNE) in serum, synovial fluid and tissue of patients with inflammatory arthritis in relation to in vivo hypoxia levels, disease activity and angiogenic markers. METHODS: Oxygen levels in synovial tissue were assessed using an oxygen\\/temperature probe. Nuclear and cytoplasmic 8-oxo-dG and 4-HNE levels were assessed in synovial tissue from 23 patients by immunohistochemistry. 8-Oxo-dG and 4-HNE levels in serum and synovial fluid were determined using 8-oxo-dG and hexanoyl-Lys (HEL) adduct ELISAs, respectively. Serum vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) levels were also measured by ELISA. RESULTS: The median oxygen tension in synovial tissue was profoundly hypoxic at 19.35 mm Hg (2.5%). Nuclear 8-oxo-dG levels were significantly higher than nuclear 4-HNE levels in the lining and sublining layers (all p<0.001). In contrast, cytoplasmic 4-HNE levels were higher than cytoplasmic 8-oxo-dG levels in both cell layers (all p<0.001). Reduced in vivo oxygen tension correlated with high lipid peroxidation in synovial fluid (p=0.027; r=0.54) and tissue (p=0.004; r=0.58). Serum VEGF levels were positively correlated with cytoplasmic 4-HNE expression (p=0.05; r=0.43) and intensity (p=0.006; r=0.59) in the lining layer. Serum Ang2 levels were positively correlated with nuclear 4-HNE expression and intensity in both cell layers (all p < or = 0.05). DAS28-C-reactive protein was correlated with nuclear 4-HNE expression in the sublining layer (p=0.02; r=0.48) and DAS28-erythrocyte sedimentation rate was correlated with nuclear 4-HNE expression in both cell layers (p < or = 0.03). CONCLUSIONS: Lipid peroxidation is associated with low oxygen tension in vivo, disease activity and angiogenic marker expression in inflammatory arthritis.

Changes in Nitric Oxide Level and Thickness Index of Synovial Fluid ...

African Journals Online (AJOL)

patients after intra-articular injection of sodium hyaluronate, while the effect is insignificant in severe patients. Thus, sodium hyaluronate can effectively improve nitric oxide levels in synovial fluid, reduce ..... Modern Med Health, 2014; 1:.

Changes in Nitric Oxide Level and Thickness Index of Synovial Fluid ...

African Journals Online (AJOL)

Changes in Nitric Oxide Level and Thickness Index of Synovial Fluid in Osteoarthritis Patients ... Tropical Journal of Pharmaceutical Research ... and moderate phase patients after intra-articular injection of sodium hyaluronate, while the effect ...

Persistence of collagen type II-specific T-cell clones in the synovial membrane of a patient with rheumatoid arthritis

International Nuclear Information System (INIS)

Londei, M.; Savill, C.M.; Verhoef, A.; Brennan, F.; Leech, Z.A.; Feldmann, M.; Duance, V.; Maini, R.N.

1989-01-01

Rheumatoid arthritis is an autoimmune disease characterized by T-cell infiltration of the synovium of joints. Analysis of the phenotype and antigen specificity of the infiltrating cells may thus provide insight into the pathogenesis of rheumatoid arthritis. T cells were cloned with interleukin 2, a procedure that selects for in vivo-activated cells. All clones had the CD4 CDW29 phenotype. Their antigen specificity was tested by using a panel of candidate joint autoantigens. Four of 17 reacted against autologous blood mononuclear cells. Two clones proliferated in response to collagen type II. After 21 months, another set of clones was derived from synovial tissue of the same joint. One of eight clones tested showed a strong proliferative response against collagen type II. The uncloned synovial T cells of a third operation from another joint also responded to collagen type II. The persistence of collagen type II-specific T cells in active rheumatoid joints over a period of 3 years suggests that collagen type II could be one of the autoantigens involved in perpetuating the inflammatory process in rheumatoid arthritis

A SYNOVIAL SARCOMA WITH A COMPLEX T(X/18/5/4) AND A BREAK IN THE ORNITHINE AMINOTRANSFERASE (OAT)LI CLUSTER ON XP11.2

NARCIS (Netherlands)

WEGHUIS, DO; STOEPKER, MEJ; DELEEUW, B; VANDENBERG, E; SUIJKERBUIJK, RF; MOLENAAR, WM; DEJONG, B; VANKESSEL, AG

The initial cytogenetic analysis of a biphasic synovial sarcoma revealed complex anomalies involving six different chromosomes: 46,Y,t(X;18;5;4)(p11;q11;p13;q12),t(2;5)(q35;q11). After fluorescence in situ hybridization (FISH) analysis, using chromosome X-specific plasmid library and YAC probes, the

Complementing xeroderma pigmentosum fibroblasts restore biological activity to UV-damaged DNA

International Nuclear Information System (INIS)

Day, R.S. III; Kraemer, K.H.; Robbins, J.H.

1975-01-01

UV survival curves of adenovirus 2 using fused complementing xeroderma pigmentosum fibroblast strains as virus hosts showed a component with an inactivation slope identical to that given by normal cells. This component was not observed when the fibroblasts were not fused or when fusions involved strains in the same complementing group. Extrapolation to zero dose indicated that three percent of the viral plaque-forming units had infected cells capable of normal repair; this suggested that three percent of the cells were complementing heterokaryons. Thus, heterokaryons formed from xeroderma pigmentosum fibroblasts belonging to different complementation groups are as capable of restoring biological activity to UV-damaged adenovirus 2 as are normal cells

The synovial microenvironment of osteoarthritic joints alters RNA-seq expression profiles of human primary articular chondrocytes

Science.gov (United States)

Lewallen, Eric A.; Bonin, Carolina A.; Li, Xin; Smith, Jay; Karperien, Marcel; Larson, A. Noelle; Lewallen, David G.; Cool, Simon M.; Westendorf, Jennifer J.; Krych, Aaron J.; Leontovich, Alexey A.; Im, Hee-Jeong; van Wijnen, Andre J.

2018-01-01

Osteoarthritis (OA) is a disabling degenerative joint disease that prompts pain with limited treatment options. To permit early diagnosis and treatment of OA, a high resolution mechanistic understanding of human chondrocytes in normal and diseased states is necessary. In this study, we assessed the biological effects of OA-related changes in the synovial microenvironment on chondrocytes embedded within anatomically intact cartilage from joints with different pathological grades by next generation RNA-sequencing (RNA-seq). We determined the transcriptome of primary articular chondrocytes derived from pristine knees and ankles, as well as from joints affected by OA. The GALAXY bioinformatics platform was used to facilitate biological interpretations. Comparisons of patient samples by k-means, hierarchical clustering and principal component analysis reveal that primary chondrocytes exhibit OA grade-related differences in gene expression, including genes involved in cell-adhesion, ECM production and immune response. We conclude that diseased synovial microenvironments in joints with different histopathological OA grades directly alter gene expression in chondrocytes. One ramification of this finding is that sampling anatomically intact cartilage from OA joints is not an ideal source of healthy chondrocytes, nor should they be used to generate a normal baseline for the molecular characterization of diseased joints. PMID:27378743

N-cadherin is overexpressed in Crohn's stricture fibroblasts and promotes intestinal fibroblast migration.

LENUS (Irish Health Repository)

Burke, John P

2012-02-01

BACKGROUND: Intestinal fibroblasts mediate stricture formation in Crohn\\'s disease (CD). Transforming growth factor-beta (TGF-beta) is important in fibroblast activation, while cell attachment and migration is regulated by the adhesion molecule N-cadherin. The aim of this study was to investigate the expression and function of N-cadherin in intestinal fibroblasts in patients with fibrostenosing CD. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies from patients undergoing resection for terminal ileal fibrostenosing CD (n = 14) or controls patients (n = 8). N-cadherin expression was assessed using Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Fibroblasts were stimulated with TGF-beta and selective pathway inhibitors Y27632, PD98050, and LY294002 were used to examine the Rho\\/ROCK, ERK-1\\/2, and Akt signaling pathways, respectively. Cell migration was assessed using a scratch wound assay. N-cadherin was selectively overexpressed using a plasmid. RESULTS: Fibroblasts from fibrostenosing CD express increased constitutive N-cadherin mRNA and protein and exhibit enhanced basal cell migration relative to those from directly adjacent normal bowel. Control fibroblasts treated with TGF-beta induced N-cadherin in a dose-dependent manner which was inhibited by Rho\\/ROCK and Akt pathway modulation. Control fibroblasts exhibited enhanced cell migration in response to treatment with TGF-beta or transfection with an N-cadherin plasmid. CONCLUSIONS: Fibroblasts from strictures in CD express increased constitutive N-cadherin and exhibit enhanced basal cell migration. TGF-beta is a potent inducer of N-cadherin in intestinal fibroblasts resulting in enhanced cell migration. The TGF-beta-mediated induction of N-cadherin may potentiate Crohn\\'s stricture formation.

Magnetic Capture of a Molecular Biomarker from Synovial Fluid in a Rat Model of Knee Osteoarthritis.

Science.gov (United States)

Yarmola, Elena G; Shah, Yash; Arnold, David P; Dobson, Jon; Allen, Kyle D

2016-04-01

Biomarker development for osteoarthritis (OA) often begins in rodent models, but can be limited by an inability to aspirate synovial fluid from a rodent stifle (similar to the human knee). To address this limitation, we have developed a magnetic nanoparticle-based technology to collect biomarkers from a rodent stifle, termed magnetic capture. Using a common OA biomarker--the c-terminus telopeptide of type II collagen (CTXII)--magnetic capture was optimized in vitro using bovine synovial fluid and then tested in a rat model of knee OA. Anti-CTXII antibodies were conjugated to the surface of superparamagnetic iron oxide-containing polymeric particles. Using these anti-CTXII particles, magnetic capture was able to estimate the level of CTXII in 25 μL aliquots of bovine synovial fluid; and under controlled conditions, this estimate was unaffected by synovial fluid viscosity. Following in vitro testing, anti-CTXII particles were tested in a rat monoiodoacetate model of knee OA. CTXII could be magnetically captured from a rodent stifle without the need to aspirate fluid and showed tenfold changes in CTXII levels from OA-affected joints relative to contralateral control joints. Combined, these data demonstrate the ability and sensitivity of magnetic capture for post-mortem analysis of OA biomarkers in the rat.

Rho family GTP binding proteins are involved in the regulatory volume decrease process in NIH3T3 mouse fibroblasts

DEFF Research Database (Denmark)

Pedersen, Stine F; Beisner, Kristine H; Willumsen, Berthe M

2002-01-01

The role of Rho GTPases in the regulatory volume decrease (RVD) process following osmotic cell swelling is controversial and has so far only been investigated for the swelling-activated Cl- efflux. We investigated the involvement of RhoA in the RVD process in NIH3T3 mouse fibroblasts, using wild......-type cells and three clones expressing constitutively active RhoA (RhoAV14). RhoAV14 expression resulted in an up to fourfold increase in the rate of RVD, measured by large-angle light scattering. The increase in RVD rate correlated with RhoAV14 expression. RVD in wild-type cells was unaffected by the Rho...

Wnt/beta-catenin signaling interacts differentially with Ihh signaling in controlling endochondral bone and synovial joint formation.

Science.gov (United States)

Mak, Kingston Kinglun; Chen, Miao-Hsueh; Day, Timothy F; Chuang, Pao-Tien; Yang, Yingzi

2006-09-01

Both the Wnt/beta-catenin and Ihh signaling pathways play essential roles in crucial aspects of endochondral ossification: osteoblast differentiation, chondrocyte proliferation and hypertrophy. To understand the genetic interaction between these two signaling pathways, we have inactivated the beta-catenin gene and upregulated Ihh signaling simultaneously in the same cells during endochondral skeletal development using beta-catenin and patched 1 floxed alleles. We uncovered previously unexpected roles of Ihh signaling in synovial joint formation and the essential function of Wnt/beta-catenin signaling in regulating chondrocyte survival. More importantly, we found that Wnt and Ihh signaling interact with each other in distinct ways to control osteoblast differentiation, chondrocyte proliferation, hypertrophy, survival and synovial joint formation in the developing endochondral bone. Beta-catenin is required downstream of Ihh signaling and osterix expression for osteoblast differentiation. But in chondrocyte survival, beta-catenin is required upstream of Ihh signaling to inhibit chondrocyte apoptosis. In addition, Ihh signaling can inhibit chondrocyte hypertrophy and synovial joint formation independently of beta-catenin. However, there is a strong synergistic interaction between Wnt/beta-catenin and Ihh signaling in regulating synovial joint formation.

Synovial sarcoma of primary bone origin: a rare case in a rare site with atypical features

International Nuclear Information System (INIS)

Jung, Seung Chai; Choi, Jung-Ah; Lee, Joon Woo; Kang, Heung Sik; Chung, Jin-Haeng; Oh, Joo Han

2007-01-01

Synovial sarcoma of bone origin is extremely rare and difficult to diagnose. We present a case in which the lesion arose in the cortex of the distal tibia. It showed heterogeneous intermediate signal intensity on T1-weighted images and heterogeneous intermediate to low signal intensity on T2-weighted images with heterogeneous contrast enhancement on MRI. The lesion was confirmed as synovial sarcoma using a combination of histological and molecular genetic studies. (orig.)

In vitro and in vivo spin echo diffusion imaging characteristics of synovial fluid: potential non-invasive differentiation of inflammatory and degenerative arthritis

International Nuclear Information System (INIS)

Eustace, S.; DiMasi, M.; Adams, J.; Ward, R.; Caruthers, S.; McAlindon, T.

2000-01-01

Objective. This study was undertaken to analyse the diffusion characteristics of synovial fluid in degenerative and inflammatory arthropathies.Design and patients. Ten in vitro specimens of synovial fluid from patients with both degenerative and inflammatory arthropathy were studied at body temperature with a navigator-corrected spin echo diffusion sequence (B values 0-512 s/mm 2 ), on a Philips 1.5-T Gyroscan. Subsequently synovial fluid from knee joint effusions of 25 patients (10 patients with osteoarthritis, 10 patients with effusions following trauma and 5 patients with effusions secondary to inflammatory arthritis) was evaluated with the same navigator-corrected spin echo diffusion sequence.Results. Both in vitro and in vivo study demonstrated decreased diffusion in patients with effusions secondary to degenerative joint disease (less than 2.40 x 10 -5 cm 2 /s) relative to patients with effusions accompanying knee trauma (greater than 2.75 x 10 -5 cm 2 /s) and inflammatory arthritis (in vitro and in vivo greater than 3.00 x 10 -5 cm 2 /s).Conclusion. Synovial fluid in degenerative arthritis shows less diffusion or free water movement than synovial fluid in inflammatory arthritis. Diffusion characteristics of synovial fluid may be used to predict the nature of the underlying form of arthritis in patients presenting with knee joint effusions. (orig.)

A synovial sarcoma with a complex t(X;18;5;4) and a break in the ornithine aminotransferase (OAT)L1 cluster on Xp11.2.

NARCIS (Netherlands)

Weghuis, D Olde; Stoepker, M E; Leeuw, B de; van den Berg, Eva; Suijkerbuijk, R F; Molenaar, W M; Jong, B de; Kessel, A Geurts van

1994-01-01

The initial cytogenetic analysis of a biphasic synovial sarcoma revealed complex anomalies involving six different chromosomes: 46,Y,t(X;18;5;4)(p11;q11;p13;q12),t(2;5)(q35;q11). After fluorescence in situ hybridization (FISH) analysis, using chromosome X-specific plasmid library and YAC probes, the

Nemosis, a novel way of fibroblast activation, in inflammation and cancer

Energy Technology Data Exchange (ETDEWEB)

Vaheri, Antti, E-mail: antti.vaheri@helsinki.fi [Haartman Institute, POB 21, FI-00014 University of Helsinki (Finland); Enzerink, Anna; Raesaenen, Kati; Salmenperae, Pertteli [Haartman Institute, POB 21, FI-00014 University of Helsinki (Finland)

2009-06-10

Malignant cells when grown in suspension, as a rule, proliferate and can form spheroids that have been used as a model of tumor nodules, micrometastases and avascular tumors. In contrast, normal adherent cells cannot be stimulated to grow as multicellular aggregates. Now, recent results show that normal fibroblasts if forced to cluster (spheroid formation) do not grow but undergo a new pathway of cell activation (nemosis) leading to a massive proinflammatory, proteolytic and growth factor response. The clustering and activation are initiated by fibronectin-integrin interaction. The activated fibroblasts are able to modulate the behavior of cancer cells and, furthermore malignant cells boost this activation even further. In this model, the activation of fibroblasts terminates in programmed necrosis-like cell death. Activation of the tumor stroma, especially of fibroblasts, is of critical importance for tumor progression, although mechanisms leading to their activation are still largely uncharacterized. In summary, our results suggest that this kind of fibroblast activation (nemosis) may be involved in pathological conditions such as inflammation and cancer.

Nemosis, a novel way of fibroblast activation, in inflammation and cancer

International Nuclear Information System (INIS)

Vaheri, Antti; Enzerink, Anna; Raesaenen, Kati; Salmenperae, Pertteli

2009-01-01

Malignant cells when grown in suspension, as a rule, proliferate and can form spheroids that have been used as a model of tumor nodules, micrometastases and avascular tumors. In contrast, normal adherent cells cannot be stimulated to grow as multicellular aggregates. Now, recent results show that normal fibroblasts if forced to cluster (spheroid formation) do not grow but undergo a new pathway of cell activation (nemosis) leading to a massive proinflammatory, proteolytic and growth factor response. The clustering and activation are initiated by fibronectin-integrin interaction. The activated fibroblasts are able to modulate the behavior of cancer cells and, furthermore malignant cells boost this activation even further. In this model, the activation of fibroblasts terminates in programmed necrosis-like cell death. Activation of the tumor stroma, especially of fibroblasts, is of critical importance for tumor progression, although mechanisms leading to their activation are still largely uncharacterized. In summary, our results suggest that this kind of fibroblast activation (nemosis) may be involved in pathological conditions such as inflammation and cancer.

Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy.

Science.gov (United States)

Baeten, Dominique; Kruithof, Elli; De Rycke, Leen; Boots, Anemieke M; Mielants, Herman; Veys, Eric M; De Keyser, Filip

2005-01-01

Considering the relation between synovial inflammation and global disease activity in rheumatoid arthritis (RA) and the distinct but heterogeneous histology of spondyloarthropathy (SpA) synovitis, the present study analyzed whether histopathological features of synovium reflect specific phenotypes and/or global disease activity in SpA. Synovial biopsies obtained from 99 SpA and 86 RA patients with active knee synovitis were analyzed for 15 histological and immunohistochemical markers. Correlations with swollen joint count, serum C-reactive protein concentrations, and erythrocyte sedimentation rate were analyzed using classical and multiparameter statistics. SpA synovitis was characterized by higher vascularity and infiltration with CD163+ macrophages and polymorphonuclear leukocytes (PMNs) and by lower values for lining-layer hyperplasia, lymphoid aggregates, CD1a+ cells, intracellular citrullinated proteins, and MHC-HC gp39 complexes than RA synovitis. Unsupervised clustering of the SpA samples based on synovial features identified two separate clusters that both contained different SpA subtypes but were significantly differentiated by concentration of C-reactive protein and erythrocyte sedimentation rate. Global disease activity in SpA correlated significantly with lining-layer hyperplasia as well as with inflammatory infiltration with macrophages, especially the CD163+ subset, and with PMNs. Accordingly, supervised clustering using these synovial parameters identified a cluster of 20 SpA patients with significantly higher disease activity, and this finding was confirmed in an independent SpA cohort. However, multiparameter models based on synovial histopathology were relatively poor predictors of disease activity in individual patients. In conclusion, these data indicate that inflammatory infiltration of the synovium with CD163+ macrophages and PMNs as well as lining-layer hyperplasia reflect global disease activity in SpA, independently of the SpA subtype

CTRP6 inhibits fibrogenesis in TGF-β1-stimulated human dermal fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Fan, Rong-hui, E-mail: fan_ronghuixa@163.com [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China); Zhu, Xiu-mei; Sun, Yao-wen [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China); Peng, Hui-zi [Department of Cosmetology Plastic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061 (China); Wu, Hang-li; Gao, Wen-jie [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China)

2016-07-08

Skin fibrosis is characterized by excessive proliferation of fibroblasts and overproduction of extracellular matrix (ECM). C1q/tumor necrosis factor-related protein 6 (CTRP6), a member of CTRPs, has been involved in the development of cardiac fibrosis. However, the function and detailed regulatory mechanism of CTRP6 in skin fibrosis remain unclear. The aim of this study was to investigate the effect of CTRP6 on the activation of human dermal fibroblasts. Our results showed that CTRP6 was lowly expressed in scar tissues and transforming growth factor-β1 (TGF-β1)-treated dermal fibroblasts. CTRP6 overexpression significantly inhibited the proliferation of dermal fibroblasts, as well as suppressed the expression of ECM in TGF-β1-treated dermal fibroblasts. Furthermore, CTRP6 overexpression markedly inhibited TGF-β1-induced phosphorylation of Smad3 in dermal fibroblasts. In conclusion, the data reported here demonstrate that CTRP6 is able to inhibit the proliferation and ECM expression in human dermal fibroblasts through suppressing the TGF-β1/Smad3 signaling pathway. These findings suggest that CTRP6 may be a potential therapeutic target for the prevention of skin fibrosis. -- Highlights: •CTRP6 expression was decreased in scar tissues and TGF-β1-treated dermal fibroblasts. •CTRP6 inhibits TGF-β1-induced the proliferation of dermal fibroblasts. •CTRP6 inhibits expression of collagen type I and α-SMA. •CTRP6 inhibits the activation of TGF-β1/Smad3 signaling pathway in dermal fibroblasts.

CTRP6 inhibits fibrogenesis in TGF-β1-stimulated human dermal fibroblasts

International Nuclear Information System (INIS)

Fan, Rong-hui; Zhu, Xiu-mei; Sun, Yao-wen; Peng, Hui-zi; Wu, Hang-li; Gao, Wen-jie

2016-01-01

Skin fibrosis is characterized by excessive proliferation of fibroblasts and overproduction of extracellular matrix (ECM). C1q/tumor necrosis factor-related protein 6 (CTRP6), a member of CTRPs, has been involved in the development of cardiac fibrosis. However, the function and detailed regulatory mechanism of CTRP6 in skin fibrosis remain unclear. The aim of this study was to investigate the effect of CTRP6 on the activation of human dermal fibroblasts. Our results showed that CTRP6 was lowly expressed in scar tissues and transforming growth factor-β1 (TGF-β1)-treated dermal fibroblasts. CTRP6 overexpression significantly inhibited the proliferation of dermal fibroblasts, as well as suppressed the expression of ECM in TGF-β1-treated dermal fibroblasts. Furthermore, CTRP6 overexpression markedly inhibited TGF-β1-induced phosphorylation of Smad3 in dermal fibroblasts. In conclusion, the data reported here demonstrate that CTRP6 is able to inhibit the proliferation and ECM expression in human dermal fibroblasts through suppressing the TGF-β1/Smad3 signaling pathway. These findings suggest that CTRP6 may be a potential therapeutic target for the prevention of skin fibrosis. -- Highlights: •CTRP6 expression was decreased in scar tissues and TGF-β1-treated dermal fibroblasts. •CTRP6 inhibits TGF-β1-induced the proliferation of dermal fibroblasts. •CTRP6 inhibits expression of collagen type I and α-SMA. •CTRP6 inhibits the activation of TGF-β1/Smad3 signaling pathway in dermal fibroblasts.

Increased synovial tissue NF-kappa B1 expression at sites adjacent to the cartilage-pannus junction in rheumatoid arthritis.

NARCIS (Netherlands)

Benito, M.J.; Murphy, E.P.; Berg, W.B. van den; Fitzgerald, O.; Bresnihan, B.

2004-01-01

OBJECTIVE: To compare the expression of the Rel/NF-kappa B subunits, NF-kappa B1 (p50) and RelA (p65), in paired synovial tissue samples selected from sites adjacent to and remote from the cartilage-pannus junction (CPJ) in patients with inflammatory arthritis. METHODS: Synovial tissue was selected

Type II collagen C2C epitope in human synovial fluid and serum after knee injury

DEFF Research Database (Denmark)

Kumahashi, N; Swärd, P; Larsson, S

2015-01-01

PURPOSE: Investigate in a cross-sectional study time-dependent changes of synovial fluid type II collagen epitope C2C concentrations after knee injury and correlate to other joint injury biomarkers. METHODS: Synovial fluid samples were aspirated between 0 days and 7 years after injury (n = 235...... = 0.403, P type II collagen (r = 0.444, P = 0.003), ARGS-aggrecan (r = 0.337, P ... with an immediate and sustained local degradation of type II collagen....

Transplantation of autologous synovial mesenchymal stem cells promotes meniscus regeneration in aged primates.

Science.gov (United States)

Kondo, Shimpei; Muneta, Takeshi; Nakagawa, Yusuke; Koga, Hideyuki; Watanabe, Toshifumi; Tsuji, Kunikazu; Sotome, Shinichi; Okawa, Atsushi; Kiuchi, Shinji; Ono, Hideo; Mizuno, Mitsuru; Sekiya, Ichiro

2017-06-01

Transplantation of aggregates of synovial mesenchymal stem cells (MSCs) enhanced meniscus regeneration in rats. Anatomy and biological properties of the meniscus depend on animal species. To apply this technique clinically, it is valuable to investigate the use of animals genetically close to humans. We investigated whether transplantation of aggregates of autologous synovial MSCs promoted meniscal regeneration in aged primates. Chynomolgus primates between 12 and 13 years old were used. After the anterior halves of the medial menisci in both knees were removed, an average of 14 aggregates consisting of 250,000 synovial MSCs were transplanted onto the meniscus defect. No aggregates were transplanted to the opposite knee for the control. Meniscus and articular cartilage were analyzed macroscopically, histologically, and by MRI T1rho mapping at 8 (n = 3) and 16 weeks (n = 4). The medial meniscus was larger and the modified Pauli's histological score for the regenerated meniscus was better in the MSC group than in the control group in each primate at 8 and 16 weeks. Mankin's score for the medial femoral condyle cartilage was better in the MSC group than in the control group in all primates at 16 weeks. T1rho value for both the regenerated meniscus and adjacent articular cartilage in the MSC group was closer to the normal meniscus than in the control group in all primates at 16 weeks. Transplantation of aggregates of autologous synovial MSCs promoted meniscus regeneration and delayed progression of degeneration of articular cartilage in aged primates. This is the first report dealing with meniscus regeneration in primates. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1274-1282, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Changes in synovial membrane and joint effusion volumes after intraarticular methylprednisolone. Quantitative assessment of inflammatory and destructive changes in arthritis by MRI

DEFF Research Database (Denmark)

Østergaard, Mikkel; Stoltenberg, M; Gideon, P

1996-01-01

OBJECTIVE: To evaluate synovial membrane volumes, effusion volumes, and cartilage and bone erosion scores determined by magnetic resonance imaging (MRI) as markers of disease activity and severity in arthritis. METHODS: Gadolinium-DTPA enhanced MRI of 18 arthritic knees was performed before and 1......, 7, 30 and 180 days after intraarticular methylprednisolone injection until clinical relapse. Intraobserver, interobserver, and inter-MRI variations were determined from 2 successive MRI of another 6 knees. RESULTS: In all knees synovial membrane and effusion volumes decreased within the first...... posttreatment week (median decrease 49 and 65%, respectively), and remained low during remission. Synovial volumes, but not effusion volumes, increased to pretreatment levels in case of clinical relapse, indicating that synovial volumes were most important to the clinical appearance. The intraobserver...

Synovial sarcoma in children and adolescents: the European Pediatric Soft Tissue Sarcoma Study Group prospective trial (EpSSG NRSTS 2005)

NARCIS (Netherlands)

Ferrari, A.; de Salvo, G. L.; Brennan, B.; van Noesel, M. M.; de Paoli, A.; Casanova, M.; Francotte, N.; Kelsey, A.; Alaggio, R.; Oberlin, O.; Carli, M.; Ben-Arush, M.; Bergeron, C.; Merks, J. H. M.; Jenney, M.; Stevens, M. C.; Bisogno, G.; Orbach, D.

2015-01-01

To report the results of the first European prospective nonrandomized trial dedicated to pediatric synovial sarcoma. From August 2005 to August 2012, 138 patients <21 years old with nonmetastatic synovial sarcoma were registered in 9 different countries (and 60 centers). Patients were treated with a

Synovial hemangiomas of the knee: magnetic resonance findings in six cases; Hemangiomas sinoviales de rodilla: hallazgos de la resonancia magnetica en seis casos

Energy Technology Data Exchange (ETDEWEB)

Concepcion, L.; Marti-Bonmati, L. M.; Dosda, R. [Hospital Dr. Peset. Valencia (Spain); Llauger, J.; Palmer, J. [Hospital Santa Creu i Sant Pau. Barcelona (Spain); Mellado, J. M. [Inscanner, S. L. Alicante (Spain)

1999-05-01

The synovial hemangioma is an uncommon benign vascular tumor that is difficult to diagnose on the basis of clinical signs Moreover, it has no characteristic radiographic features. The objective of the present report was to describe the MR findings associated with synovial hemangioma of the knee. We review the clinical and MR findings in six patients, with histologically confirmed synovial hemangioma of the Knee, studied with different MR systems and techniques. Synovial hemangiomas were isointense with respect to muscle in T1-weighted images, strongly hyperintense in T2-weighted sequences and presented wavy hypointense linear images. Gadolinium administration resulted in a marked enhancement, although it was heterogeneous in two of three cases analyzed. Although the findings are not pathognomonic, the presence of an intraarticular tumor of the knee that is isointense with respect to muscle in T1 and hyperintense in T2, and shows wavy hypointense images and a marked contrast uptake, may suggest the presence of synovial hemangioma. (Author) 11 refs.

Localization of surfactant protein-D in the rheumatoid synovial membrane

DEFF Research Database (Denmark)

Christensen, Anne Friesgaard; Sorensen, Grith Lykke; Junker, Kirsten

2018-01-01

and subsequently prepared for immunohistochemistry. In this first, small-scale comparative study on the occurrence of SP-D in the synovial membrane of RA and OA, we report that SP-D was only present in the microvascular endothelium in subsynovial and pannus tissue and that the immunostaining was much stronger than...

Descriptions of therapeutic arthrocenthesis and of synovial fluid in a Nahuatl text from prehispanic Mexico.

Science.gov (United States)

Alarcon-Segovia, D

1980-06-01

Paracelsus is considered to have been the first to record the viscid quality of the synovial fluid. However, his contemporary Bernardino de Sahagún, a Franciscan friar who came to Mexico shortly after the Spanish conquest, obtained from elderly Aztec Indians who spoke only Nahuatl the descriptions of therapeutic arthrocentesis and of the viscid nature of the synovial fluid. They compared the fluid from the knee joint to the viscid fluid from the leaves of the nopal cactus (Opuntia sp.). We here record their description and confirm the accuracy of their comparison.

Fibroblast spheroids as a model to study sustained fibroblast quiescence and their crosstalk with tumor cells

Energy Technology Data Exchange (ETDEWEB)

Salmenperä, Pertteli, E-mail: pertteli.salmenpera@helsinki.fi [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland); Karhemo, Piia-Riitta [Research Programs Unit, Translational Cancer Biology, and Institute of Biomedicine, University of Helsinki, P.O. Box 63, FIN-00014 (Finland); Räsänen, Kati [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland); Laakkonen, Pirjo [Research Programs Unit, Translational Cancer Biology, and Institute of Biomedicine, University of Helsinki, P.O. Box 63, FIN-00014 (Finland); Vaheri, Antti [Department of Virology, Medicum, Faculty of Medicine, University of Helsinki, P.O. Box 21, FIN-00014 (Finland)

2016-07-01

Stromal fibroblasts have an important role in regulating tumor progression. Normal and quiescent fibroblasts have been shown to restrict and control cancer cell growth, while cancer-associated, i. e. activated fibroblasts have been shown to enhance proliferation and metastasis of cancer cells. In this study we describe generation of quiescent fibroblasts in multicellular spheroids and their effects on squamous cell carcinoma (SCC) growth in soft-agarose and xenograft models. Quiescent phenotype of fibroblasts was determined by global down-regulation of expression of genes related to cell cycle and increased expression of p27. Interestingly, microarray analysis showed that fibroblast quiescence was associated with similar secretory phenotype as seen in senescence and they expressed senescence-associated-β-galactosidase. Quiescent fibroblasts spheroids also restricted the growth of RT3 SCC cells both in soft-agarose and xenograft models unlike proliferating fibroblasts. Restricted tumor growth was associated with marginally increased tumor cell senescence and cellular differentiation, showed with senescence-associated-β-galactosidase and cytokeratin 7 staining. Our results show that the fibroblasts spheroids can be used as a model to study cellular quiescence and their effects on cancer cell progression. - Highlights: • Fibroblasts acquire a sustained quiescence when grown as multicellular spheroids. • This quiescence is associated with drastic change in gene expression. • Fibroblasts spheroids secrete various inflammation-linked cytokines and chemokines. • Fibroblasts spheroids reduced growth of RT3 SCC cells in xenograft model.

Testosterone metabolism of fibroblasts grown from prostatic carcinoma, benign prostatic hyperplasia and skin fibroblasts

International Nuclear Information System (INIS)

Schweikert, H.U.; Hein, H.J.; Romijn, J.C.; Schroeder, F.H.

1982-01-01

The metabolism of [1,2,6,7-3H]testosterone was assessed in fibroblast monolayers derived from tissue of 5 prostates with benign hyperplasia (BPH), 4 prostates with carcinoma (PC), and 3 biopsy samples of skin, 2 nongenital skin (NG) and 1 genital skin. The following metabolites could be identified: androstanedione androstenedione, dihydrotestosterone, androsterone, epiandrosterone, androstane-3 alpha, 17 beta-diol and androstane-3 beta, 17 beta-diol. Testosterone was metabolized much more rapidly in fibroblasts originating from prostatic tissue than in fibroblasts derived from NG. A significantly higher formation of 5 alpha-androstanes and 3 alpha-hydroxysteroids could be observed in fibroblasts from BPH as compared to PC. 17-ketosteroid formation exceeded 5 alpha-androstane formation in BPH, whereas 5 alpha-reduction was the predominant pathway in fibroblasts grown from PC and NG. Since testosterone metabolism in fibroblasts of prostatic origin therefore resembles in many aspects that in whole prostatic tissue, fibroblasts grown from prostatic tissues might be a valuable tool for further investigation of the pathogenesis of human BPH and PC

Adiponectin and Leptin Synovial Fluid Concentration as a Marker for the Severity of Knee Osteoarthritis in Obese Patients

Directory of Open Access Journals (Sweden)

Eddy Mart Salim

2015-12-01

Full Text Available Purpose: Osteoarthritis (OA is a chronic degenerative joint disorder of the synovial joint characterized by loss of articular cartilage, osteophyte formation, and alterations of subchondral bone. An increase of weight bearing affect on knee joint biomechanically and alter concentration of adipokines, such as adiponectin and leptin. Herein we reported a correlation between adiponectin and leptin synovial fluid concentration with the severity of knee OA in obese patients. Material and Methods: Totally 45 patients were included in this research. ELISA was used to determine adiponectin and leptin concentrations of synovial fluid. The severity of knee OA was classified by Kellgren-Lawrence grading scale. Data analysis was conducted using SPSS for windows. Results: Based on the leptin measurement, it was shown that leptin concentrations were correlated positively with the severity of knee OA. Vice versa, adiponectin concentrations were correlated negative. Conclusion: Our study was support the biomarker function of adiponectin and leptin concentration on synovial fluids, in which those concentrations were related with the severity of OA. Those results also suggested the function of leptin and adiponectin on OA. [Cukurova Med J 2015; 40(4.000: 746-756

Synovial folds in the knee joint

International Nuclear Information System (INIS)

Schaefer, H.

1987-01-01

Stimulated by arthroscopic insight into central abnormalities of the knee joint and by the large number of unexplained case of 'anterior knee pain', we have studied the synovia in more than 2000 contrast examinations of the joint. Surprisingly, and contrary to the views expressed in the literature, the clinically significant plica parapatellaris medialis was seen as frequently during pneumo-arthrography as during more complex procedures. Abnormalities in the synovial fold emerged as a discreet disease identified as the 'medial shelf syndrome' and should be included in the differential diagnosis of causes of pain round the lower end of the femur and patella. (orig.) [de

Epidural cystic masses associated with interspinous bursitis, synovial and discal cysts

International Nuclear Information System (INIS)

Santos, Frederico Guilherme de Paula Lopes; Souza, Ricardo Andre de; Brotto, Marcos Pama D'Almeida; Suguita, Fabio Massaaki; Amaral, Denise Tokechi; Amaral, Lazaro Luis Faria do

2009-01-01

The authors describe some cases of epidural cysts, namely synovial, discal, ligamentum flavum cysts, and cysts secondary to interspinous bursitis, all of these conditions determining radicular, dural sac compression or spinal canal stenosis. Magnetic resonance imaging findings and localization of these entities are described. (author)

Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis

NARCIS (Netherlands)

Noordenbos, Troy; Yeremenko, Nataliya; Gofita, Ioana; van de Sande, Marleen; Tak, Paul P.; Caňete, Juan D.; Baeten, Dominique

2012-01-01

Objective Studies comparing spondylarthritis (SpA) to rheumatoid arthritis (RA) synovitis suggest that innate immune cells may play a predominant role in the pathogenesis of SpA. Recent observations have indicated a marked synovial mast cell infiltration in psoriatic SpA. We therefore undertook the

Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis.

Science.gov (United States)

Lupia, E; Montrucchio, G; Battaglia, E; Modena, V; Camussi, G

1996-08-01

The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.

Synovial cell production of IL-26 induces bone mineralization in spondyloarthritis

DEFF Research Database (Denmark)

Heftdal, Line Dam; Andersen, Thomas; Jæhger, Ditte

2017-01-01

expression in SpA patients, and examine the in vitro production of IL-26 by synovial cells and the effects of IL-26 on human osteoblasts. IL-26 was measured by ELISA in plasma and synovial fluid (SF) of 15 SpA patients and in plasma samples from 12 healthy controls. Facet joints from axial SpA patients were...... and the myofibroblast marker α-smooth-muscle-actin (αSMA) and analyzed by flow cytometry. Human osteoblasts were cultured in the presence of IL-26, and the degree of mineralization was quantified. We found that IL-26 levels in SF were increased compared with plasma (P ... in facet joints of axial SpA patients within the bone marrow. IL-26 secretion was primarily found in αSMA(+) myofibroblasts. In contrast, Th17 cells did not produce detectable amounts of IL-26. Human osteoblasts treated with IL-26 showed increased mineralization compared with untreated osteoblasts (P = 0...

High expression of SDF-1 and VEGF is associated with poor prognosis in patients with synovial sarcomas.

Science.gov (United States)

Feng, Qi; Guo, Peng; Wang, Jin; Zhang, Xiaoyu; Yang, Hui-Chai; Feng, Jian-Gang

2018-03-01

Stromal cell-derived factor-1 (SDF-1) predicts poor clinical outcomes of certain types of cancer. Furthermore, vascular endothelial growth factor (VEGF) promotes the growth and metastasis of solid tumors. The aim of the present study was to examine the expression of SDF-1 and VEGF in patients with synovial sarcoma and to determine their expression is correlated with unfavorable outcomes. Levels of SDF-1 and VEGF proteins were evaluated in 54 patients with synovial sarcoma using immunohistochemical and immunofluorescence staining. Potential associations between the expression of SDF-1 and VEGF and various clinical parameters were analyzed using Pearson's χ 2 test and the Spearman-rho test. Additionally, univariate and multivariate Cox regression analyses were used to identify potential prognostic factors, and the Kaplan-Meier method was used to analyze the overall survival rates of patients. Low SDF-1 and VEGF expression was detected in 20.4% (11/54) and 22.2% (12/54) of patients with synovial sarcoma; moderate expression was detected in 35.2% (19/54) and 37.0% (20/54) of patients and high expression was detected in 44.4% (24 of 54) and 40.7% (22 of 54) of patients, respectively. Levels of SDF-1 and VEGF proteins were significantly associated with histological grade (P<0.05), metastasis (P<0.05) and American Joint Committee on Cancer staging (P<0.05). In addition, levels of SDF-1 and VEGF expression were positively correlated with each other (P<0.001). Univariate analysis also indicated that VEGF expression was associated with shorter overall survival rates in (P<0.05), whereas multivariate analysis demonstrated that SDF-1 expression was associated with shorter patient survival rates (P<0.05). Finally, both SDF-1 and VEGF expression were associated with various characteristics of synovial sarcoma. Therefore, SDF-1 expression may be a potential independent prognostic indicator in patients with synovial sarcomas.

TRIF promotes angiotensin II-induced cross-talk between fibroblasts and macrophages in atrial fibrosis

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Chen, Xiao-Qing; Zhang, Dao-Liang [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China); Zhang, Ming-Jian; Guo, Meng; Zhan, Yang-Yang; Liu, Fang [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Jiang, Wei-Feng; Zhou, Li [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China); Zhao, Liang, E-mail: zhaol_zg@163.com [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China); Wang, Quan-Xing, E-mail: wqxejd@126.com [National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai (China); Liu, Xu, E-mail: liuxu_xk@163.com [Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai (China)

2015-08-14

Aims: Atrial fibroblasts and macrophages have long been thought to participate in atrial fibrillation (AF). However, which specific mediator may regulate the interaction between them remains unclear. Methods and results: We provided the evidence for the involvement of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF), an important inflammation-related molecule, in the pathophysiology of AF. Patients with AF showed higher levels of angiotensin II (AngII) and TRIF expression and larger number of macrophages infiltration in left atria appendage than individuals with sinus rhythm (SR). In the cell study, AngII induced chemokines expressions in mouse atrial fibroblasts and AngII-stimulated atrial fibroblasts induced the chemotaxis of macrophages, which were reduced by losartan and TRIF siRNA. Meanwhile, AngII-stimulated atrial fibroblasts proliferation was enhanced by macrophages. Conclusions: Our data demonstrated that TRIF may be a crucial factor promoting the interaction between atrial fibroblasts and macrophages, leading to atrial fibrosis. - Highlights: • Compared with SR, AF showed higher TRIF expression in left atrial appendage. • TRIF siRNA reversed macrophage chemotaxis induced by AngII-treated fibroblast. • TRIF siRNA reversed chemokines expressions induced by AngII in fibroblast. • AngII-stimulated atrial fibroblast proliferation was enhanced by macrophage.

TRIF promotes angiotensin II-induced cross-talk between fibroblasts and macrophages in atrial fibrosis

International Nuclear Information System (INIS)

Chen, Xiao-Qing; Zhang, Dao-Liang; Zhang, Ming-Jian; Guo, Meng; Zhan, Yang-Yang; Liu, Fang; Jiang, Wei-Feng; Zhou, Li; Zhao, Liang; Wang, Quan-Xing; Liu, Xu

2015-01-01

Aims: Atrial fibroblasts and macrophages have long been thought to participate in atrial fibrillation (AF). However, which specific mediator may regulate the interaction between them remains unclear. Methods and results: We provided the evidence for the involvement of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF), an important inflammation-related molecule, in the pathophysiology of AF. Patients with AF showed higher levels of angiotensin II (AngII) and TRIF expression and larger number of macrophages infiltration in left atria appendage than individuals with sinus rhythm (SR). In the cell study, AngII induced chemokines expressions in mouse atrial fibroblasts and AngII-stimulated atrial fibroblasts induced the chemotaxis of macrophages, which were reduced by losartan and TRIF siRNA. Meanwhile, AngII-stimulated atrial fibroblasts proliferation was enhanced by macrophages. Conclusions: Our data demonstrated that TRIF may be a crucial factor promoting the interaction between atrial fibroblasts and macrophages, leading to atrial fibrosis. - Highlights: • Compared with SR, AF showed higher TRIF expression in left atrial appendage. • TRIF siRNA reversed macrophage chemotaxis induced by AngII-treated fibroblast. • TRIF siRNA reversed chemokines expressions induced by AngII in fibroblast. • AngII-stimulated atrial fibroblast proliferation was enhanced by macrophage

Isolation of Chlamydia trachomatis or Ureaplasma urealyticum from the synovial fluid of patients with Reiter's syndrome

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Pavlica Ljiljana

2003-01-01

Full Text Available Background. The aim of this study was to contribute to the insight of the role of the infectious agent in ethiopathogenesis of the Reiter’s syndrome development, which could directly influence the choise of treatment of these patients. Methods. Eighteen patients with urogenital form of the Reiter’s syndrome and 16 controls (6 with rheumatoid arthritis and 10 with pigmented villonodular synovitis were included in the study. In all patients standard laboratory analyses of the blood, urine and stool were made; antibody titer to Chlamydia trachomatis and Ureaplasma urealyticum was determined in synovial fluid and serum; isolation of Chlamydia trachomatis and Ureaplasma urealyticum in urethral, cervical and conjunctival swabs, as well as in prostatic and synovial fluid, was also made. HLA typing was done, too. Chlamydia was isolated in the McCoy cell culture treated with cycloheximide while Ureaplasma was identified according to its biochemical properties grown on cell-free liquid medium. Results. Chlamydia trachomatis was isolated from the synovial fluid of 4 patients with Reiter's syndrome 22.2%, while Ureaplasma urealyticum was isolated in 7 of them (38.9%. These microorganisms were not found in any synovial fluid of the control group patients. Conclusion. Presence of these bacteria in the inflamed joint might be an important factor in etiopathogenesis of this disease, and it supports the hypothesis that arthritis in Reiter's syndrome is probably of the infectious origin.

Cervical synovial sarcoma in a young boy | Fisher | South African ...

African Journals Online (AJOL)

Synovial sarcomas comprise about 8% of all tumours of somatic soft-tissues, and are the most common sarcomas of the 'hands and feet. Occasionally they may occur in the trunk, but they have rarely been reported in the neck. We present a case of cervical soft-tissue mass producing symptoms in a 12-year-old-boy.

Sphingolipids in human synovial fluid--a lipidomic study.

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Marta Krystyna Kosinska

Full Text Available Articular synovial fluid (SF is a complex mixture of components that regulate nutrition, communication, shock absorption, and lubrication. Alterations in its composition can be pathogenic. This lipidomic investigation aims to quantify the composition of sphingolipids (sphingomyelins, ceramides, and hexosyl- and dihexosylceramides and minor glycerophospholipid species, including (lysophosphatidic acid, (lysophosphatidylglycerol, and bis(monoacylglycerophosphate species, in the SF of knee joints from unaffected controls and from patients with early (eOA and late (lOA stages of osteoarthritis (OA, and rheumatoid arthritis (RA. SF without cells and cellular debris from 9 postmortem donors (control, 18 RA, 17 eOA, and 13 lOA patients were extracted to measure lipid species using electrospray ionization tandem mass spectrometry--directly or coupled with hydrophilic interaction liquid chromatography. We provide a novel, detailed overview of sphingolipid and minor glycerophospholipid species in human SF. A total of 41, 48, and 50 lipid species were significantly increased in eOA, lOA, and RA SF, respectively when compared with normal SF. The level of 21 lipid species differed in eOA SF versus SF from lOA, an observation that can be used to develop biomarkers. Sphingolipids can alter synovial inflammation and the repair responses of damaged joints. Thus, our lipidomic study provides the foundation for studying the biosynthesis and function of lipid species in health and most prevalent joint diseases.

Surgical treatment of synovial osteochondromatosis of the hip using a modified-Hardinge approach with a Z-shaped capsular incision

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Yu Takeda

2015-12-01

Full Text Available Synovial osteochondromatosis of the hip is a rare condition, and the surgical treatment approach for this condition requires complete removal of loose bodies combined with synovectomy. While these, procedures are generally accepted as the optimal treatment method, this is still controversial topic. Recent studies have reported that open surgical procedures remain acceptable for synovial osteochondromatosis of the hip. These procedures include the dislocation of the femoral head, and complications such as femoral head necrosis and bursitis or great trochanter non-union due to trochanteric osteotomy have been reported. The present study reports a modified technique for surgical dislocation through a Z-shaped capsular incision without trochanteric flip osteotomy for the treatment of synovial osteochondromatosis of the hip.

Simultaneous Reprogramming and Gene Correction of Patient Fibroblasts

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Sara E. Howden

2015-12-01

Full Text Available The derivation of genetically modified induced pluripotent stem (iPS cells typically involves multiple steps, requiring lengthy cell culture periods, drug selection, and several clonal events. We report the generation of gene-targeted iPS cell lines following a single electroporation of patient-specific fibroblasts using episomal-based reprogramming vectors and the Cas9/CRISPR system. Simultaneous reprogramming and gene targeting was tested and achieved in two independent fibroblast lines with targeting efficiencies of up to 8% of the total iPS cell population. We have successfully targeted the DNMT3B and OCT4 genes with a fluorescent reporter and corrected the disease-causing mutation in both patient fibroblast lines: one derived from an adult with retinitis pigmentosa, the other from an infant with severe combined immunodeficiency. This procedure allows the generation of gene-targeted iPS cell lines with only a single clonal event in as little as 2 weeks and without the need for drug selection, thereby facilitating “seamless” single base-pair changes.

Sciatica as the first manifestation of synovial sarcoma. Contribution of magnetic resonance imaging to the diagnosis; Sciatique revelatrice d`un synovialosarcome. Interet de l`IRM

Energy Technology Data Exchange (ETDEWEB)

Veillard, E.; Le Dantec, P.; Chales, G.; Jean, S.; Pawlotsky, Y. [Centre Hospitalier Universitaire, 35 - Rennes (France)

1995-07-01

A 38-year-old man presented with paralyzing sciatica as the first manifestation of synovial sarcoma of his right leg. Although neurologic symptoms sometimes occur as manifestations of synovial sarcoma, they are exceptionally inaugural. Magnetic resonance imaging is a valuable tool in patients with synovial tumors, both for establishing the diagnosis and for evaluating the extent of the lesion. (authors). 13 refs., 3 figs.

Comparative lipidomic analysis of synovial fluid in human and canine osteoarthritis

NARCIS (Netherlands)

Kosinska, M. K.; Mastbergen, S. C.; Liebisch, G.; Wilhelm, J.; Dettmeyer, R. B.; Ishaque, B.; Rickert, M.; Schmitz, G.; Lafeber, F. P.; Steinmeyer, J.

Objective: The lipid profile of synovial fluid (SF) is related to the health status of joints. The early stages of human osteoarthritis (OA) are poorly understood, which larger animals are expected to be able to model closely. This study examined whether the canine groove model of OA represents

[Destruction of synovial pannus of antigen-induced arthritis by ultrasonic cavitation in rabbits].

Science.gov (United States)

Zhang, Ling-yan; Qiu, Li; Wang, Lei; Lin, Ling; Wen, Xiao-rong

2011-11-01

To optimize the conditions of ultrasonic irradiation and microbubble of ultrasound cavitation on destruction of synovial pannus of antigen-induced arthritis (AIA) in rabbits. Antigen-induced arthritis was successfully induced on bilateral knee joints of 85 rabbits. Each 10 AIA rabbits were divided into two groups to compare various peak negative pressures, different ultrasonic pulse durations, various pulse repetition frequencies, different irradiance duration, different dosages of microbubble contrast agents, different ultrasonic irradiance times. With intravenous infusion of Sonovue to the rabbits, ultrasonic irradiance was performed on the right knee joint using the above condition of ultrasound cavitation. At the day 1 after ultrasonic irradiance, MRI and pathological examination were employed to evaluate the optimal conditions. The optimal parameters and conditions for ultrasonic irradiance included intermittent ultrasonic application (in 6 s intervals), 0.6 mL/kg of microbubble contrast agent, 4.6 MPa of ultrasonic peak negative pressure, 100 cycles of pulse duration, 50 Hz of pulse repetition frequency, 5 min of ultrasonic duration, 0.6 mL/kg of dosages of microbubble contrast agents and multi-sessional ultrasonic irradiance. After the ultrasonic irradiance, the thickness of right knee synovium measured by MRI was thinner than that of left knee and synovial necrosis was confirmed by the pathological finding. Under optimal ultrasonic irradiation and microbubble conditions, ultrasonic cavitation could destroy synovial pannus of AIA in rabbits.

Disposition of methylprednisolone acetate in plasma, urine, and synovial fluid following intra-articular administration to exercised thoroughbred horses.

Science.gov (United States)

Knych, H K; Harrison, L M; Casbeer, H C; McKemie, D S

2014-04-01

Methylprednisolone acetate (MPA) is commonly administered to performance horses, and therefore, establishing appropriate withdrawal times prior to performance is critical. The objectives of this study were to describe the plasma pharmacokinetics of MPA and time-related urine and synovial fluid concentrations following intra-articular administration to sixteen racing fit adult Thoroughbred horses. Horses received a single intra-articular administration of MPA (100 mg). Blood, urine, and synovial fluid samples were collected prior to and at various times up to 77 days postdrug administration and analyzed using tandem liquid chromatography-mass spectrometry (LC-MS/MS). Maximum measured plasma MPA concentrations were 6.06 ± 1.57 at 0.271 days (6.5 h; range: 5.0-7.92 h) and 6.27 ± 1.29 ng/mL at 0.276 days (6.6 h; range: 4.03-12.0 h) for horses that had synovial fluid collected (group 1) and those that did not (group 2), respectively. The plasma terminal half-life was 1.33 ± 0.80 and 0.843 ± 0.414 days for groups 1 and 2, respectively. MPA was undetectable by day 6.25 ± 2.12 (group 1) and 4.81 ± 2.56 (group 2) in plasma and day 17 (group 1) and 14 (group 2) in urine. MPA concentrations in synovial fluid remained above the limit of detection (LOD) for up to 77 days following intra-articular administration, suggesting that plasma and urine concentrations are not a good indicator of synovial fluid concentrations. © 2013 John Wiley & Sons Ltd.

Differential roles of SS18-SSX fusion gene and insulin-like growth factor-1 receptor in synovial sarcoma cell growth

International Nuclear Information System (INIS)

Toernkvist, Maria; Natalishvili, Natalia; Xie Yuntao; Girnita, Ada; D'Arcy, Padraig; Brodin, Bertha; Axelson, Magnus; Girnita, Leonard

2008-01-01

Recently we demonstrated that the synovial sarcoma specific fusion gene SS18-SSX is crucial for cyclin D1 expression and is linked to cell proliferation. In this report we explore the role of SS18-SSX and IGF-1R for their potential functions in cellular proliferation and survival in cultured synovial sarcoma cells. We found that targeting of SS18-SSX mRNA by antisense oligonucleotide treatment drastically and rapidly decreased cell proliferation but caused only a slight increase of apoptosis. The synovial sarcoma cells were confirmed to express IGF-1R, and treatment with an IGF-1R inhibitor resulted in substantially reduced cell viability by inducing apoptosis in these cells. Conversely, inhibition of the IGF-1R resulted only in a slight to moderate decrease in DNA synthesis. In conclusion, SS18-SSX and IGF-1R seem to play important but different roles in maintaining malignant growth of synovial sarcoma cells. Whereas SS18-SSX maintains cyclin D1 and cell proliferation, IGF-1R protects from apoptosis

Synovial chondromatosis of the lumbar spine with compressive myelopathy: a case report with review of the literature

International Nuclear Information System (INIS)

Abdelwahab, Ibrahim Fikry; Contractor, Daniel; Bianchi, Stefano; Hermann, George; Hoch, Benjamin

2008-01-01

Synovial chondromatosis has been rarely reported to occur in the spine with only one case found in the lumbar spine. We describe another case of synovial chondromatosis in the lumbar spine in a 41-year-old man who presented with compressive myelopathy. The tumor was located in the left ventrolateral corner of the epidural space just below the L 4 -L 5 intervertebral space. Besides being extremely rare, our case was unusual in that the juxtaposed facet joint was radiologically normal. (orig.)

Exosome-mediated delivery of miR-9 induces cancer-associated fibroblast-like properties in human breast fibroblasts

Science.gov (United States)

Baroni, S; Romero-Cordoba, S; Plantamura, I; Dugo, M; D'Ippolito, E; Cataldo, A; Cosentino, G; Angeloni, V; Rossini, A; Daidone, M G; Iorio, M V

2016-01-01

It is established that the interaction between microenvironment and cancer cells has a critical role in tumor development, given the dependence of neoplastic cells on stromal support. However, how this communication promotes the activation of normal (NFs) into cancer-associated fibroblasts (CAFs) is still not well understood. Most microRNA (miRNA) studies focused on tumor cell, but there is increasing evidence of their involvement in reprogramming NFs into CAFs. Here we show that miR-9, upregulated in various breast cancer cell lines and identified as pro-metastatic miRNA, affects the properties of human breast fibroblasts, enhancing the switch to CAF phenotype, thus contributing to tumor growth. Expressed at higher levels in primary triple-negative breast CAFs versus NFs isolated from patients, miR-9 improves indeed migration and invasion capabilities when transfected in immortalized NFs; viceversa, these properties are strongly impaired in CAFs upon miR-9 inhibition. We also demonstrate that tumor-secreted miR-9 can be transferred via exosomes to recipient NFs and this uptake results in enhanced cell motility. Moreover, we observed that this miRNA is also secreted by fibroblasts and in turn able to alter tumor cell behavior, by modulating its direct target E-cadherin, and NFs themselves. Consistently with the biological effects observed, gene expression profiles of NFs upon transient transfection with miR-9 show the modulation of genes mainly involved in cell motility and extracellular matrix remodeling pathways. Finally, we were able to confirm the capability of NFs transiently transfected with miR-9 to promote in vivo tumor growth. Taken together, these data provide new insights into the role of miR-9 as an important player in the cross-talk between cancer cells and stroma. PMID:27468688

Oral fibroblasts produce more HGF and KGF than skin fibroblasts in response to co-culture with keratinocytes

DEFF Research Database (Denmark)

Grøn, Birgitte; Stoltze, Kaj; Andersson, Anders

2002-01-01

The production of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) in subepithelial fibroblasts from buccal mucosa, periodontal ligament, and skin was determined after co-culture with keratinocytes. The purpose was to detect differences between the fibroblast subpopulations...... days by ELISA. When cultured on polystyrene, the constitutive level of KGF and HGF in periodontal fibroblasts was higher than the level in buccal and skin fibroblasts. In the presence of keratinocytes, all three types of fibroblasts in general increased their HGF and KGF production 2-3 times. When...... cells were maintained in collagen, the level of HGF and KGF was decreased mainly in skin cultures. However, in oral fibroblasts, induction after stimulation was at a similar level in collagen compared to on polystyrene. Skin fibroblasts maintained in collagen produced almost no HGF whether...

Cultured Human Fibroblast Biostimulation Using a 940 nm Diode Laser

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Illescas-Montes, Rebeca; Melguizo-Rodríguez, Lucía; Manzano-Moreno, Francisco Javier; García-Martínez, Olga; Ruiz, Concepción

2017-01-01

Background: Fibroblasts are the main cells involved in regeneration during wound healing. The objective was to determine the effect of 940 nm diode laser on cultured human fibroblasts using different irradiation regimens. Methods: The CCD-1064Sk human epithelial fibroblast cell line was treated with a 940 nm diode laser at different energy doses (power: 0.2–1 W and energy density: 1–7 J/cm2) using different transmission modes (continuous or pulsed). The effect on cell growth at 24 and 72 h post-treatment was examined by measuring the proliferative capacity, the impact on the cell cycle, and the effect on cell differentiation. Results: fibroblast proliferative capacity was increased at 24 and 72 h post-treatment as a function of the energy dose. The greatest increase was observed with a power of 0.2 or 0.5 W and energy density between 1 and 4 J/cm2; no difference was observed between continuous and pulsed modes. There were no significant differences in cell cycle between treated groups and controls. α-actin expression was increased by treatment, indicating enhanced cell differentiation. Conclusion: The 940 nm diode laser has biostimulating effects on fibroblasts, stimulating proliferative capacity and cell differentiation without altering the cell cycle. Further researches are necessary to explore its potential clinical usefulness in wound healing. PMID:28773152

Cultured Human Fibroblast Biostimulation Using a 940 nm Diode Laser

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Rebeca Illescas-Montes

2017-07-01

Full Text Available Background: Fibroblasts are the main cells involved in regeneration during wound healing. The objective was to determine the effect of 940 nm diode laser on cultured human fibroblasts using different irradiation regimens. Methods: The CCD-1064Sk human epithelial fibroblast cell line was treated with a 940 nm diode laser at different energy doses (power: 0.2–1 W and energy density: 1–7 J/cm2 using different transmission modes (continuous or pulsed. The effect on cell growth at 24 and 72 h post-treatment was examined by measuring the proliferative capacity, the impact on the cell cycle, and the effect on cell differentiation. Results: fibroblast proliferative capacity was increased at 24 and 72 h post-treatment as a function of the energy dose. The greatest increase was observed with a power of 0.2 or 0.5 W and energy density between 1 and 4 J/cm2; no difference was observed between continuous and pulsed modes. There were no significant differences in cell cycle between treated groups and controls. α-actin expression was increased by treatment, indicating enhanced cell differentiation. Conclusion: The 940 nm diode laser has biostimulating effects on fibroblasts, stimulating proliferative capacity and cell differentiation without altering the cell cycle. Further researches are necessary to explore its potential clinical usefulness in wound healing.

Reduced superoxide dismutase activity in xeroderma pigmentosum fibroblasts

International Nuclear Information System (INIS)

Nishigori, C.; Miyachi, Y.; Imamura, S.; Takebe, H.

1989-01-01

This study was performed in order to assess the possible protective effect of superoxide dismutase (SOD) on ultraviolet (UV) damage in xeroderma pigmentosum (XP) fibroblasts. SOD activity in fibroblasts originating from seven xeroderma pigmentosum (XP) patients was significantly lower than that in normal cells (p less than 0.005). Average SOD activity in XP cells belonging to complementation group A was 3.68 +/- 0.54 (n = 7) and that in normal human cells was 5.79 +/- 1.59 (n = 6). Addition of SOD before and during UV irradiation (UVB and UVC) to the cells caused no change in the amount of unscheduled DNA synthesis and UV survival. A possible involvement of reduced SOD in XP and a possible protective effect by SOD on UV damage is discussed

Synovial Chondromatosis of the Subacromial Bursa Causing a Bursal-Sided Rotator Cuff Tear

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Julie A. Neumann

2015-01-01

Full Text Available Synovial chondromatosis is an uncommon condition, and involvement of the shoulder is even more rare. We report on a 39-year-old female who presented with symptoms, radiographic features, and intraoperative findings consistent with multiple subacromial loose bodies resulting in a partial-thickness, bursal-sided rotator cuff tear of the supraspinatus muscle. She was treated with an arthroscopic removal of loose bodies, complete excision of the subacromial/subdeltoid bursa, acromioplasty, and rotator cuff repair. To our knowledge, this is the first report of arthroscopic treatment for a bursal-sided, partial-thickness rotator cuff tear treated with greater than two-year clinical and radiographic follow-up. We utilized shoulder scores, preoperative and postoperative range of motion, and imaging to assess the results of treatment and surveillance for recurrence in our patient after two-year follow-up.

Suppression of murine collagen-induced arthritis by targeted apoptosis of synovial neovasculature

NARCIS (Netherlands)

Gerlag, D. M.; Borges, E.; Tak, P. P.; Ellerby, H. M.; Bredesen, D. E.; Pasqualini, R.; Ruoslahti, E.; Firestein, G. S.

2001-01-01

Because angiogenesis plays a major role in the perpetuation of inflammatory arthritis, we explored a method for selectively targeting and destroying new synovial blood vessels. Mice with collagen-induced arthritis were injected intravenously with phage expressing an RGD motif. In addition, the RGD

Synovial hemangioma of the knee: MRI findings in two cases

International Nuclear Information System (INIS)

Llauger, J.; Monill, J.M.; Palmer, J.; Clotet, M.

1995-01-01

The findings in two patients with histologically proven synovial hemangioma of the knee are described. Both cases emphasize the typical appearance of this unusual tumor on magnetic resonance imaging. Additional radiologic findings, such as adjacent osseous insolvement, are discussed. The MRI findings of this tumor are highly suggestive of the diagnosis and MRI should eliminate the need for invasive angiographic procedures. (orig.)

Tubule-Derived Wnts Are Required for Fibroblast Activation and Kidney Fibrosis.

Science.gov (United States)

Zhou, Dong; Fu, Haiyan; Zhang, Lu; Zhang, Ke; Min, Yali; Xiao, Liangxiang; Lin, Lin; Bastacky, Sheldon I; Liu, Youhua

2017-08-01

Cell-cell communication via Wnt ligands is necessary in regulating embryonic development and has been implicated in CKD. Because Wnt ligands are ubiquitously expressed, the exact cellular source of the Wnts involved in CKD remains undefined. To address this issue, we generated two conditional knockout mouse lines in which Wntless (Wls), a dedicated cargo receptor that is obligatory for Wnt secretion, was selectively ablated in tubular epithelial cells or interstitial fibroblasts. Blockade of Wnt secretion by genetic deletion of Wls in renal tubules markedly inhibited myofibroblast activation and reduced renal fibrosis after unilateral ureteral obstruction. This effect associated with decreased activation of β -catenin and downstream gene expression and preserved tubular epithelial integrity. In contrast, fibroblast-specific deletion of Wls exhibited little effect on the severity of renal fibrosis after obstructive or ischemia-reperfusion injury. In vitro , incubation of normal rat kidney fibroblasts with tubule-derived Wnts promoted fibroblast proliferation and activation. Furthermore, compared with kidney specimens from patients without CKD, biopsy specimens from patients with CKD also displayed increased expression of multiple Wnt proteins, predominantly in renal tubular epithelium. These results illustrate that tubule-derived Wnts have an essential role in promoting fibroblast activation and kidney fibrosis via epithelial-mesenchymal communication. Copyright © 2017 by the American Society of Nephrology.

A model of synovial fluid lubricant composition in normal and injured joints

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M E Blewis

2007-03-01

Full Text Available The synovial fluid (SF of joints normally functions as a biological lubricant, providing low-friction and low-wear properties to articulating cartilage surfaces through the putative contributions of proteoglycan 4 (PRG4, hyaluronic acid (HA, and surface active phospholipids (SAPL. These lubricants are secreted by chondrocytes in articular cartilage and synoviocytes in synovium, and concentrated in the synovial space by the semi-permeable synovial lining. A deficiency in this lubricating system may contribute to the erosion of articulating cartilage surfaces in conditions of arthritis. A quantitative intercompartmental model was developed to predict in vivo SF lubricant concentration in the human knee joint. The model consists of a SF compartment that (a is lined by cells of appropriate types, (b is bound by a semi-permeable membrane, and (c contains factors that regulate lubricant secretion. Lubricant concentration was predicted with different chemical regulators of chondrocyte and synoviocyte secretion, and also with therapeutic interventions of joint lavage and HA injection. The model predicted steady-state lubricant concentrations that were within physiologically observed ranges, and which were markedly altered with chemical regulation. The model also predicted that when starting from a zero lubricant concentration after joint lavage, PRG4 reaches steady-state concentration ~10-40 times faster than HA. Additionally, analysis of the clearance rate of HA after therapeutic injection into SF predicted that the majority of HA leaves the joint after ~1-2 days. This quantitative intercompartmental model allows integration of biophysical processes to identify both environmental factors and clinical therapies that affect SF lubricant composition in whole joints.

Quantitation of the repair of gamma-radiation-induced double-strand DNA breaks in human fibroblasts

International Nuclear Information System (INIS)

Woods, W.G.

1981-01-01

The quantitation and repair of double-strand DNA breaks in human fibroblasts has been determined using a method involving the nondenaturing elution of DNA from a filter. DNA from cells from two human fibroblast lines exposed to γ-radiation from 0 to 10000 rad showed increasing retention on a filter with decreasing radiation dose, and the data suggest a linear relationship between double-strand breaks induced and radiation dose. The ability of normal human fibroblasts to repair double-strand breaks with various doses of radiation was demonstrated, with a tsub(1/2) of 10 min for repair of 5000 rad exposure and 39 min for repair of 10000 rad damage. The kinetics of the DNA rejoining were not linear and suggest that, as in the repair of single-strand breaks, both an initial fast and a later slow mechanism may be involved. (Auth.)

X ray sensitivity of diploid skin fibroblasts from patients with Fanconi's anemia

Science.gov (United States)

Kale, Ranjini

1989-01-01

Experiments were performed on Fanconi's anemia and normal human fibroblast cell lines growing in culture in an attempt to correlate cell cycle kinetics with genomic damage and determine their bearing on the mechanism of chromosome aberration induction. FA fibroblasts showed a significantly increased susceptibility to chromosomal breakage by x rays in the G2 phase of the cell cycle. No such response was observed in fibroblasts irradiated in the G0 phase. The observed increases in achromatic lesions and in chromatid deletions in FA cells as compared with normal cells appear to indicate that FA cells are deficient in strand break repair and also possibly in base damage excision repair. Experiments are now in progress to further elucidate the mechanisms involved.

Identification of specific gene expression profiles in fibroblasts derived from middle ear cholesteatoma.

Science.gov (United States)

Yoshikawa, Mamoru; Kojima, Hiromi; Wada, Kota; Tsukidate, Toshiharu; Okada, Naoko; Saito, Hirohisa; Moriyama, Hiroshi

2006-07-01

To investigate the role of fibroblasts in the pathogenesis of cholesteatoma. Tissue specimens were obtained from our patients. Middle ear cholesteatoma-derived fibroblasts (MECFs) and postauricular skin-derived fibroblasts (SFs) as controls were then cultured for a few weeks. These fibroblasts were stimulated with interleukin (IL) 1alpha and/or IL-1beta before gene expression assays. We used the human genome U133A probe array (GeneChip) and real-time polymerase chain reaction to examine and compare the gene expression profiles of the MECFs and SFs. Six patients who had undergone tympanoplasty. The IL-1alpha-regulated genes were classified into 4 distinct clusters on the basis of profiles differentially regulated by SF and MECF using a hierarchical clustering analysis. The messenger RNA expressions of LARC (liver and activation-regulated chemokine), GMCSF (granulocyte-macrophage colony-stimulating factor), epiregulin, ICAM1 (intercellular adhesion molecule 1), and TGFA (transforming growth factor alpha) were more strongly up-regulated by IL-1alpha and/or IL-1beta in MECF than in SF, suggesting that these fibroblasts derived from different tissues retained their typical gene expression profiles. Fibroblasts may play a role in hyperkeratosis of middle ear cholesteatoma by releasing molecules involved in inflammation and epidermal growth. These fibroblasts may retain tissue-specific characteristics presumably controlled by epigenetic mechanisms.

The hallmarks of fibroblast ageing.

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Tigges, Julia; Krutmann, Jean; Fritsche, Ellen; Haendeler, Judith; Schaal, Heiner; Fischer, Jens W; Kalfalah, Faiza; Reinke, Hans; Reifenberger, Guido; Stühler, Kai; Ventura, Natascia; Gundermann, Sabrina; Boukamp, Petra; Boege, Fritz

2014-06-01

Ageing is influenced by the intrinsic disposition delineating what is maximally possible and extrinsic factors determining how that frame is individually exploited. Intrinsic and extrinsic ageing processes act on the dermis, a post-mitotic skin compartment mainly consisting of extracellular matrix and fibroblasts. Dermal fibroblasts are long-lived cells constantly undergoing damage accumulation and (mal-)adaptation, thus constituting a powerful indicator system for human ageing. Here, we use the systematic of ubiquitous hallmarks of ageing (Lopez-Otin et al., 2013, Cell 153) to categorise the available knowledge regarding dermal fibroblast ageing. We discriminate processes inducible in culture from phenomena apparent in skin biopsies or primary cells from old donors, coming to the following conclusions: (i) Fibroblasts aged in culture exhibit most of the established, ubiquitous hallmarks of ageing. (ii) Not all of these hallmarks have been detected or investigated in fibroblasts aged in situ (in the skin). (iii) Dermal fibroblasts aged in vitro and in vivo exhibit additional features currently not considered ubiquitous hallmarks of ageing. (iv) The ageing process of dermal fibroblasts in their physiological tissue environment has only been partially elucidated, although these cells have been a preferred model of cell ageing in vitro for decades. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Targeted gene delivery to the synovial pannus in antigen-induced arthritis by ultrasound-targeted microbubble destruction in vivo.

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Xiang, Xi; Tang, Yuanjiao; Leng, Qianying; Zhang, Lingyan; Qiu, Li

2016-02-01

The purpose of this study was to optimize an ultrasound-targeted microbubble destruction (UTMD) technique to improve the in vivo transfection efficiency of the gene encoding enhanced green fluorescent protein (EGFP) in the synovial pannus in an antigen-induced arthritis rabbit model. A mixture of microbubbles and plasmids was locally injected into the knee joints of an antigen-induced arthritis (AIA) rabbits. The plasmid concentrations and ultrasound conditions were varied in the experiments. We also tested local articular and intravenous injections. The rabbits were divided into five groups: (1) ultrasound+microbubbles+plasmid; (2) ultrasound+plasmid; (3) microbubble+plasmid; (4) plasmid only; (5) untreated controls. EGFP expression was observed by fluorescent microscope and immunohistochemical staining in the synovial pannus of each group. The optimal plasmid dosage and ultrasound parameter were determined based on the results of EGFP expression and the present and absent of tissue damage under light microscopy. The irradiation procedure was performed to observe the duration of the EGFP expression in the synovial pannus and other tissues and organs, as well as the damage to the normal cells. The optimal condition was determined to be a 1-MHz ultrasound pulse applied for 5 min with a power output of 2 W/cm(2) and a 20% duty cycle along with 300 μg of plasmid. Under these conditions, the synovial pannus showed significant EGFP expression without significant damage to the surrounding normal tissue. The EGFP expression induced by the local intra-articular injection was significantly more increased than that induced by the intravenous injection. The EGFP expression in the synovial pannus of the ultrasound+microbubbles+plasmid group was significantly higher than that of the other four groups (Ppannus of an AIA model. Thus, this could become a safe and effective non-viral gene transfection procedure for arthritis therapy. Copyright © 2015 Elsevier B.V. All rights

Interleukin-1β attenuates myofibroblast formation and extracellular matrix production in dermal and lung fibroblasts exposed to transforming growth factor-β1.

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Masum M Mia

Full Text Available One of the most potent pro-fibrotic cytokines is transforming growth factor (TGFβ. TGFβ is involved in the activation of fibroblasts into myofibroblasts, resulting in the hallmark of fibrosis: the pathological accumulation of collagen. Interleukin-1β (IL1β can influence the severity of fibrosis, however much less is known about the direct effects on fibroblasts. Using lung and dermal fibroblasts, we have investigated the effects of IL1β, TGFβ1, and IL1β in combination with TGFβ1 on myofibroblast formation, collagen synthesis and collagen modification (including prolyl hydroxylase, lysyl hydroxylase and lysyl oxidase, and matrix metalloproteinases (MMPs. We found that IL1β alone has no obvious pro-fibrotic effect on fibroblasts. However, IL1β is able to inhibit the TGFβ1-induced myofibroblast formation as well as collagen synthesis. Glioma-associated oncogene homolog 1 (GLI1, the Hedgehog transcription factor that is involved in the transformation of fibroblasts into myofibroblasts is upregulated by TGFβ1. The addition of IL1β reduced the expression of GLI1 and thereby also indirectly inhibits myofibroblast formation. Other potentially anti-fibrotic effects of IL1β that were observed are the increased levels of MMP1, -2, -9 and -14 produced by fibroblasts exposed to TGFβ1/IL1β in comparison with fibroblasts exposed to TGFβ1 alone. In addition, IL1β decreased the TGFβ1-induced upregulation of lysyl oxidase, an enzyme involved in collagen cross-linking. Furthermore, we found that lung and dermal fibroblasts do not always behave identically towards IL1β. Suppression of COL1A1 by IL1β in the presence of TGFβ1 is more pronounced in lung fibroblasts compared to dermal fibroblasts, whereas a higher upregulation of MMP1 is seen in dermal fibroblasts. The role of IL1β in fibrosis should be reconsidered, and the differences in phenotypical properties of fibroblasts derived from different organs should be taken into account in future

The role of synovial fluid analysis in the detection of periprosthetic hip and knee infections: a systematic review and meta-analysis.

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De Fine, Marcello; Giavaresi, Gianluca; Fini, Milena; Illuminati, Andrea; Terrando, Silvio; Pignatti, Giovanni

2018-05-01

This study tried to ascertain (1) the accuracy of synovial fluid white blood cell count and polymorphonucleate percentage in the diagnosis of periprosthetic hip and knee infections, (2) which test yielded superior test performance, and (3) the influence on diagnostic accuracy of study characteristics such as patient number, study design, study level, anatomic site, and threshold value. A systematic search was conducted including papers assessing more effective cutoffs for synovial fluid tests, having comparative design, evaluating an exclusive cohort of hip or knee prostheses, including a clear definition of infected cases, and reporting sufficient data for the calculation of true-positive, false-positive, false-negative, and true-negative. A total of 375 articles were collected and, given the inclusion criteria, ten manuscripts were included. These studies assessed 1155 hip prostheses (276 infected cases) and 1235 knee prostheses (401 infected cases). The specificity of synovial fluid white blood cell count was significantly increased by using the threshold value ≥ 3000 cell/μL (p = 0.006); the sensitivity of polymorphonucleate percentage was significantly higher in detecting knee infections (p = 0.034). Both tests had a high specificity and sensitivity in detecting periprosthetic joint infections, and no clear superiority of one over the other existed. Furthermore, cutoff and anatomic site significantly influenced synovial fluid white blood cell count and polymorphonucleate percentage, respectively. Synovial fluid analysis is adequate in differentiating patients with periprosthetic hip and knee infections. Our data confirms international guidelines suggesting the use of 3000 cell/μL as cutoff threshold for synovial fluid white blood cell count. Since an anatomic site effect has been demonstrated, the goal of future studies will be to identify different cutoffs for hip and knee prostheses.

The effect of tranilast on fibroblast activation protein α (FAP-α expression in normal and keloid fibroblasts in vitro

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Paweł P. Antończak

2017-07-01

Full Text Available Introduction . Tranilast (N-(3’,4’-demethoxycinnamoyl-anthranilic acid is an anti-allergic drug. Its mechanism of action is based on the inhibition of antigen-induced release of chemical mediators from mast cells and basophils. It also reveals antifibroproliferative activities. These properties of tranilast are used in the treatment of hypertrophic scars and keloids. Keloids are characterized by incorrect extracellular matrix components turnover. Fibroblasts derived from keloids reveal overproduction of collagen type I and decreased degradation of extracellular matrix in comparison with normal fibroblasts. Fibroblast activation protein α (FAP-α may play an important role in remodeling of extracellular matrix and the invasive properties of keloids. Objective . In the present study, the effect of tranilast on expression of FAP-α gene and its protein was evaluated in normal human dermal fibroblasts and fibroblasts derived from keloids cultured in vitro . Materials and methods. In the first stage of the study, the influence of tranilast on cell viability was estimated. The second stage of the study included the quantitative evaluation of FAP-α mRNA expression in normal and keloid fibroblasts treated with tranilast. The third stage of the study comprised fibroblast activation protein α expression analysis in the examined cells treated with tranilast. Results and conclusions . The expression of FAP-α gene and fibroblast activation protein α is higher in keloid fibroblasts. Tranilast at concentrations of 3 μM and 30 μM up-regulated mRNA FAP-α expression in normal fibroblasts but did not influence keloid fibroblasts. The drug, at concentrations of 30 μM and 300 μM up-regulated fibroblast activation protein α expression in normal fibroblasts and did not influence keloid fibroblasts. Tranilast antiproliferative effect is not associated with FAP-α expression in keloid fibroblasts.

Fibroblast growth factor receptors in breast cancer.

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Wang, Shuwei; Ding, Zhongyang

2017-05-01

Fibroblast growth factor receptors are growth factor receptor tyrosine kinases, exerting their roles in embryogenesis, tissue homeostasis, and development of breast cancer. Recent genetic studies have identified some subtypes of fibroblast growth factor receptors as strong genetic loci associated with breast cancer. In this article, we review the recent epidemiological findings and experiment results of fibroblast growth factor receptors in breast cancer. First, we summarized the structure and physiological function of fibroblast growth factor receptors in humans. Then, we discussed the common genetic variations in fibroblast growth factor receptors that affect breast cancer risk. In addition, we also introduced the potential roles of each fibroblast growth factor receptors isoform in breast cancer. Finally, we explored the potential therapeutics targeting fibroblast growth factor receptors for breast cancer. Based on the biological mechanisms of fibroblast growth factor receptors leading to the pathogenesis in breast cancer, targeting fibroblast growth factor receptors may provide new opportunities for breast cancer therapeutic strategies.

The effect of polymer size and charge of molecules on permeation through synovial membrane and accumulation in hyaline articular cartilage.

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Sterner, B; Harms, M; Wöll, S; Weigandt, M; Windbergs, M; Lehr, C M

2016-04-01

The treatment of joint related diseases often involves direct intra-articular injections. For rational development of novel delivery systems with extended residence time in the joint, detailed understanding of transport and retention phenomena within the joint is mandatory. This work presents a systematic study on the in vitro permeation, penetration and accumulation of model polymers with differing charges and molecular weights in bovine joint tissue. Permeation experiments with bovine synovial membrane were performed with PEG polymers (6-200 kDa) and methylene blue in customized diffusion chambers. For polyethylene glycol, 2-fold (PEG 6 kDa), 3-fold (PEG 10 kDa) and 13-fold (PEG 35 kDa) retention by the synovial membrane in reference to the small molecule methylene blue was demonstrated. No PEG 200 kDa was found in the acceptor in detectable amounts after 48 h. This showed the potential for a distinct extension of joint residence times by increasing molecular weights. In addition, experiments with bovine cartilage tissue were conducted. The ability for positively charged, high molecular weight chitosans and HEMA-Co-TMAP (HCT) polymers (up to 233 kDa) to distribute throughout the entire cartilage matrix was demonstrated. In contrast, a distribution into cartilage was not observed for neutral PEG polymers (6-200 kDa). Furthermore, the positive charge density of different compounds (chitosan, HEMA-Co-TMAP, methylene blue, MSC C1 (neutral NCE) and MSC D1 (positively charged NCE) was found to correlate with their accumulation in bovine cartilage tissue. In summary, the results offer pre-clinical in vitro data, indicating that the modification of molecular size and charge of a substance has the potential to decelerate its clearance through the synovial membrane and to promote accumulation inside the cartilage matrix. Copyright © 2016 Elsevier B.V. All rights reserved.

Scleral fibroblast response to experimental glaucoma in mice

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Tezel, Gülgün; Cone-Kimball, Elizabeth; Steinhart, Matthew R.; Jefferys, Joan; Pease, Mary E.; Quigley, Harry A.

2016-01-01

Purpose To study the detailed cellular and molecular changes in the mouse sclera subjected to experimental glaucoma. Methods Three strains of mice underwent experimental bead-injection glaucoma and were euthanized at 3 days and 1, 3, and 6 weeks. Scleral protein expression was analyzed with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) using 16O/18O labeling for quantification in 1- and 6-week tissues. Sclera protein samples were also analyzed with immunoblotting with specific antibodies to selected proteins. The proportion of proliferating scleral fibroblasts was quantified with Ki67 and 4’,6-diamidino-2-phenylindole (DAPI) labeling, and selected proteins were studied with immunohistochemistry. Results Proteomic analysis showed increases in molecules involved in integrin-linked kinase signaling and actin cytoskeleton signaling pathways at 1 and 6 weeks after experimental glaucoma. The peripapillary scleral region had more fibroblasts than equatorial sclera (p=0.001, n=217, multivariable regression models). There was a sixfold increase in proliferating fibroblasts in the experimental glaucoma sclera at 1 week and a threefold rise at 3 and 6 weeks (p=0.0005, univariate regression). Immunoblots confirmed increases for myosin, spectrin, and actinin at 1 week after glaucoma. Thrombospondin-1 (TSP-1), HINT1, vimentin, actinin, and α-smooth muscle actin were increased according to immunohistochemistry. Conclusions Scleral fibroblasts in experimental mouse glaucoma show increases in actin cytoskeleton and integrin-related signaling, increases in cell division, and features compatible with myofibroblast transition. PMID:26900327

Primary Pulmonary Synovial Sarcoma: A Case with Unique and Impressive Computed Tomography Findings

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Jaspreet S Kambo

2015-01-01

Full Text Available Primary pulmonary synovial sarcoma (PPSS is a rare malignancy. Its etiology, imaging features and optimal treatment are not well understood. Pulmonary pseudoaneurysms and lymphadenopathy are rare complications of synovial sarcomas. A 40-year-old woman with mild hemoptysis and thoracic back pain underwent a computed tomography scan that revealed multiple pulmonary lesions, paraesophageal lymphadenopathy and incidental bilateral pulmonary emboli. A diagnosis of PPSS was made through the identification of an SS18 translocation by fluorescence in situ hybridization. She was started on adriamycin, ifosfamide and mesna chemotherapy. Over the subsequent two months, she developed three pulmonary artery pseudoaneurysms, ultimately requiring endovascular coiling. Seven months after starting treatment, the patient was asymptomatic. The lesions and lymphadenopathy decreased in size. The present case highlights complications of a rare malignancy and demonstrates positive response to ifosfamide-based chemotherapy in the setting of PPSS.

Synovial chondromatosis of the acromioclavicular joint

International Nuclear Information System (INIS)

Kudawara, Ikuo; Aono, Masanari; Ohzono, Kenji; Mano, Masayuki

2004-01-01

A 53-year-old woman presented with swelling of 3 years' duration on the right anterior chest wall. A radiograph showed coarse calcifications around the subclavicular region and erosion of the ipsilateral acromioclavicular joint. Computed tomography also showed calcifications in soft tissue. Magnetic resonance imaging revealed a tumor around the clavicle extending to the anterior aspect of chest wall, which had low signal intensity on T1-weighted imaging and high signal intensity on T2-weighted imaging. The histologic findings were of a hyaline cartilage-like mass consisting of mature chondrocytes and an extracellular matrix. The histologic diagnosis of synovial chondromatosis was made. The present case is unusual in respect of the location and size of the tumor. (orig.)

Synovial chondromatosis of the acromioclavicular joint

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Kudawara, Ikuo; Aono, Masanari; Ohzono, Kenji [Osaka National Hospital, Department of Orthopaedic Surgery, Osaka (Japan); Mano, Masayuki [Osaka National Hospital, Department of Pathology, Osaka (Japan)

2004-10-01

A 53-year-old woman presented with swelling of 3 years' duration on the right anterior chest wall. A radiograph showed coarse calcifications around the subclavicular region and erosion of the ipsilateral acromioclavicular joint. Computed tomography also showed calcifications in soft tissue. Magnetic resonance imaging revealed a tumor around the clavicle extending to the anterior aspect of chest wall, which had low signal intensity on T1-weighted imaging and high signal intensity on T2-weighted imaging. The histologic findings were of a hyaline cartilage-like mass consisting of mature chondrocytes and an extracellular matrix. The histologic diagnosis of synovial chondromatosis was made. The present case is unusual in respect of the location and size of the tumor. (orig.)

The effect of endotoxin and anti-endotoxin serum on synovial fluid parameters in the horse

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R.D. Gottschalk

1998-07-01

Full Text Available The effects of a commercially available equine hyperimmune anti-endotoxin serum on synovial fluid parameters were evaluated in an induced synovitis model in normal horses. Four groups of 3 horses each received lipopolysaccharide (LPS plus hyperimmune antiendotoxin (anti-LPS, LPS, anti-LPS, and Ringers lactate (control respectively injected into the left intercarpal joint. Synovial fluid parameters were measured at 4, 8, 24 and 72 h. It was found that anti-LPS had no attenuating effect on the LPS and that it induced a synovitis almost equivalent to that induced by LPS alone. The introduction of sterile Ringers lactate solution into the carpal joint together with repeated aseptic arthrocentesis induces a mild inflammatory response.

Synovial haemangioma of the knee joint: an unusual cause of knee pain in a 14-month old girl.

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Wen, D W; Tan, T J; Rasheed, S

2016-06-01

We report a histologically proven case of synovial haemangioma of the knee in a 14-month old girl who presented to the emergency department with an acute 1-day history of refusing to weight-bear on the right leg and a preceding 3-week history of a right knee lump. Physical examination revealed a non-tender, soft lump over the lateral infrapatellar region. Radiographs revealed a poorly defined soft tissue density over the infrapatellar fat pad and a suprapatellar joint effusion. Ultrasound was used to confirm the presence of a vascular soft tissue mass compatible with a synovial haemangioma within the infrapatellar fat pad which showed both intra-articular and extra-articular extension. There was good correlation of the ultrasound findings with magnetic resonance imaging (MRI), highlighting the potential clinical utility of ultrasound as an alternative imaging modality in establishing the pre-operative diagnosis and extent of a synovial haemangioma about the knee joint.

Synovial haemangioma of the knee joint: an unusual cause of knee pain in a 14-month old girl

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Wen, D.W.; Rasheed, S. [KK Women' s and Children' s Hospital, Department of Diagnostic and Interventional Imaging, Singapore (Singapore); Tan, T.J. [Changi General Hospital, Department of Radiology, Singapore (Singapore)

2016-06-15

We report a histologically proven case of synovial haemangioma of the knee in a 14-month old girl who presented to the emergency department with an acute 1-day history of refusing to weight-bear on the right leg and a preceding 3-week history of a right knee lump. Physical examination revealed a non-tender, soft lump over the lateral infrapatellar region. Radiographs revealed a poorly defined soft tissue density over the infrapatellar fat pad and a suprapatellar joint effusion. Ultrasound was used to confirm the presence of a vascular soft tissue mass compatible with a synovial haemangioma within the infrapatellar fat pad which showed both intra-articular and extra-articular extension. There was good correlation of the ultrasound findings with magnetic resonance imaging (MRI), highlighting the potential clinical utility of ultrasound as an alternative imaging modality in establishing the pre-operative diagnosis and extent of a synovial haemangioma about the knee joint. (orig.)

The efficacy of 16S ribosomal DNA sequencing in the diagnosis of bacteria from blood, bone and synovial fluid samples of children with musculoskeletal infections.

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Hashavya, S; Gross, I; Michael-Gayego, A; Simanovsky, N; Lamdan, R

2018-04-01

Musculoskeletal infections are among the most common bacterial infections in children leading to hospitalization, invasive procedures and prolonged antibiotic administration. Blood, synovial and sometimes tissue cultures are essential for the diagnosis and treatment of musculoskeletal infections; 16S ribosomal DNA (rDNA) sequencing is a novel diagnostic tool for the detection of bacteria.While the yield of 16S rDNA sequencing in synovial fluid was previously assessed, data regarding the efficacy of this method from blood samples or partially treated children with suspected musculoskeletal infections is lacking.In this study we assessed the yield of 16S rDNA sequencing in blood, bone and synovial samples of children with musculoskeletal infections. Blood, synovial and bone samples were collected from children with suspected musculoskeletal infections and analyzed for the presence of 16S rDNA, the results were then compared with the benchmark microbial cultures. During the study period, 41 children (18 boys and 23 girls) with suspected acute musculoskeletal infection were enrolled. A positive blood culture was found in 6/31 cases (19.4%) with methicillin-susceptible Staphylococcus aureus being the most commonly isolated bacterium. No significant 16S rDNA detection in blood samples was recorded.Synovial fluid culture was positive in 6/28 samples (21%), Kingella kingae being the most common pathogen. When using the 16S rDNA sequencing method, the rate of positive results in synovial fluid was higher with bacterial detection in 12/23 (52%) samples. The 16S rDNA sequencing method was also able to identify pathogens in samples taken from partially treated children where cultures were negative with 16S rDNA detection in 5/5 samples. Although 16S rDNA sequencing may increase the yield of bacterial detection in synovial samples of patients with musculoskeletal infections, there is no benefit from applying this method on blood samples. The 16S rDNA sequencing method may be

Synovial sarcoma with radiological appearances of primitive neuroectodermal tumour/Ewing sarcoma: differentiation by molecular genetic studies

International Nuclear Information System (INIS)

O'Donnell, P.; Diss, T.C.; Whelan, J.; Flanagan, A.M.

2006-01-01

Synovial sarcoma (SS) arises in soft tissues but may invade adjacent bone. We describe a case of SS presenting as aggressive lysis of the proximal ulna, the imaging of which suggested a primary bone lesion. Needle biopsy showed a 'small round blue cell tumour', and a primitive neuroectodermal tumour (PNET)/Ewing sarcoma was suggested on the basis of the imaging appearances. The definitive diagnosis of synovial sarcoma was made following molecular genetic studies, which demonstrated a fusion product incorporating the genes SYT and SSX1. The importance of correct diagnosis to guide appropriate management, and, therefore, the necessity for molecular genetic studies, is discussed. (orig.)

Proliferative and inductive effects of Cyclosporine a on gingival fibroblast of child and adult

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Bahareh Nazemi Salman

2013-01-01

Conclusions: The mechanism of a CsA-induced fibroblast overgrowth may converge on the steps involving fibroblast proliferation and cytokine network including IL-6, IL-8, IL-1β, TGF-β1, and PGE 2 , in both adults and pediatrics. As the prevalence and intensity of drug-induced gingival overgrowth is more serious in the pediatrics. As group than in adults, we suggest that more studies be conducted on the pediatric group.

Protective role of microRNA-29a in denatured dermis and skin fibroblast cells after thermal injury

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Jie Zhou

2016-03-01

Full Text Available Our previous study has suggested that downregulated microRNA (miR-29a in denatured dermis might be involved in burn wound healing. However, the exact role of miR-29a in healing of burn injury still remains unclear. Here, we found that expression of miR-29a was notably upregulated in denatured dermis tissues and skin fibroblast cells after thermal injury, and thereafter gradually downregulated compared with control group. By contrast, the expression of collagen, type I, alpha 2 (COL1A2 and vascular endothelial growth factor (VEGF-A were first reduced and subsequently upregulated in denatured dermis tissues and skin fibroblast cells after thermal injury. We further identified COL1A2 as a novel target of miR-29a, which is involved in type I collagen synthesis, and showed that miR-29a negatively regulated the expression level of COL1A2 in skin fibroblast cells. In addition, VEGF-A, another target gene of miR-29a, was also negatively mediated by miR-29a in skin fibroblast cells. Inhibition of miR-29a expression significantly promoted the proliferation and migration of skin fibroblast cells after thermal injury, and knockdown of COL1A2 and VEGF-A reversed the effects of miR-29a on the proliferation and migration of skin fibroblast cells. Furthermore, we found that Notch2/Jagged2 signaling was involved in miR-29a response to burn wound healing. Our findings suggest that downregulated miR-29a in denatured dermis may help burn wound healing in the later phase, probably via upregulation of COL1A2 and VEGF-A expression, which can further enhance type I collagen synthesis and angiogenesis.

Anti-xanthine oxidase antibodies in sera and synovial fluid of patients with rheumatoid arthritis and other joint inflammations

International Nuclear Information System (INIS)

Arrar, L.; Hanachi, N.; Rouba, K.; Charef, N.; Khennouf, S.; Baghiani, A.

2008-01-01

Objective was to study anti-bovine milk xanthine oxidoreductase XOPR antibody levels in synovial fluid as well as in serum of patients suffering from rheumatoid affections to assess a possible correlation between antibody titres and severity of disease. Sera and synovial fluids were collected from volunteer donors at Setif University Hospital, Setif, Algeria from 2001-2007 with the consent of patients. Human IgG and IgM levels of free and bound anti-bovine milk XOR antibodies were determined using bovine XOR as antigen, with enzyme-linked immunosorbent assay ELISA. Serum IgG anti-bovine milk XOR titres in 30 healthy normal subjects 2.74+-2.31 microgram/mL are in agreement with that reported in the literature. Immunoglobulin G and IgM anti-bovine milk XOR antibody titres were found to be significantly higher in serum from patients with rheumatoid arthritis RA and latex positives subjects. Synovial IgM antibody titres to bovine XOR were found to be significantly higher in rheumatoid arthritis patients compared to patients with other joint inflammations. In rheumatoid arthritis patients, high concentrations of antibodies against XOR were noticed. These antibodies may play a major role in RA by inhibiting both xanthine and NADH oxidase activities of XOR. They may also play a key role in eliminating XOR from serum and synovial fluid positive role but unfortunately, immune complex formation could also activate complement and participate in self maintenance of inflammation. (author)

Anti-inflammatory and apoptotic effects of the polyphenol curcumin on human fibroblast-like synoviocytes.

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Kloesch, Burkhard; Becker, Tatjana; Dietersdorfer, Elisabeth; Kiener, Hans; Steiner, Guenter

2013-02-01

It has recently been reported that the polyphenol curcumin has pronounced anti-carcinogenic, anti-inflammatory and pro-apoptotic properties. This study investigated possible anti-inflammatory and apoptotic effects of curcumin on the human synovial fibroblast cell line MH7A, and on fibroblast-like synoviocytes (FLS) derived from patients with rheumatoid arthritis (RA). MH7A cells and RA-FLS were stimulated either with interleukin (IL)-1β or phorbol 12-myristate 13 acetate (PMA), and treated simultaneously or sequentially with increasing concentrations of curcumin. Release of interleukin (IL)-6 and vascular endothelial growth factor (VEGF)-A was quantified by enzyme-linked immunosorbent assays (ELISAs). In MH7A cells, modulation of the transcription factor nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinases (MAPKs) such as p38 and extracellular-signal regulated kinase (ERK1/2) were analysed by a reporter gene assay and Western blot, respectively. Pro-apoptotic events were monitored by Annexin-V/7-AAD based assay. Cleavage of pro-caspase-3 and -7 was checked with specific antibodies. Curcumin effectively blocked IL-1β and PMA-induced IL-6 expression both in MH7A cells and RA-FLS. VEGF-A expression could only be detected in RA-FLS and was induced by PMA, but not by IL-1β. Furthermore, curcumin inhibited activation of NF-κB and induced dephosphorylation of ERK1/2. Treatment of FLS with high concentrations of curcumin was associated with a decrease in cell viability and induction of apoptosis. The natural compound curcumin represents strong anti-inflammatory properties and induces apoptosis in FLS. This study provides an insight into possible molecular mechanisms of this substance and suggests it as a natural remedy for the treatment of chronic inflammatory diseases like RA. Copyright © 2013 Elsevier B.V. All rights reserved.

Icariin Regulates Cellular Functions and Gene Expression of Osteoarthritis Patient-Derived Human Fibroblast-Like Synoviocytes

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Lianhong Pan

2017-12-01

Full Text Available Synovial inflammation plays an important role in the pathogenesis and progress of osteoarthritis (OA. There is an urgent need to find safe and effective drugs that can reduce the inflammation and regulate the pathogenesis of cytokines of the OA disease. Here, we investigated the effect of icariin, the major pharmacological active component of herb Epimedium on human osteoarthritis fibroblast-like synoviocytes (OA–FLSs. The OA–FLSs were isolated from patients with osteoarthritis and cultured in vitro with different concentrations of icariin. Then, cell viability, proliferation, and migration were investigated; MMP14, GRP78, and IL-1β gene expression levels were detected via qRT-PCR. Icariin showed low cytotoxicity to OA–FLSs at a concentration of under 10 μM and decreased the proliferation of the cells at concentrations of 1 and 10 μM. Icariin inhibited cell migration with concentrations ranging from 0.1 to 1 μM. Also, the expression of three cytokines for the pathogenesis of OA which include IL-1β, MMP14 and GRP78 was decreased by the various concentrations of icariin. These preliminary results imply that icariin might be an effective compound for the treatment of OA disease.

Modulation of clonogenicity, growth, and radiosensitivity of three human epidermoid tumor cell lines by a fibroblastic environment

International Nuclear Information System (INIS)

Gery, Bernard; Little, John B.; Coppey, Jacques

1996-01-01

Purpose: To develop a model vitro system to examine the influence of fibroblasts on the growth and survival of human tumor cells after exposure to ionizing radiation. Methods and Materials: The cell system consists of three epidermoid carcinoma cell lines derived from head and neck tumors having differing growth potentials and intrinsic radiosensitivities, as well as a low passage skin fibroblast strain from a normal human donor. The tumor cells were seeded for five days prior to exposure to radiation: (a) in the presence of different numbers of fibroblasts, (b) in conditioned medium from stationary fibroblast cultures, and (c) on an extracted fibroblastic matrix. Results: When grown with fibroblasts, all three tumor cell lines showed increased clonogenicity and increased radioresistance. The radioprotective effect was maximal at a density of approximately 10 5 fibroblasts/100 mm Petri dish, and was greatest in the intrinsically radiosensitive tumor cell line. On the other hand, the effects of incubation with conditioned medium or on a fibroblastic matrix varied among the tumor cell lines. Thus, the protective effect afforded by coculture with fibroblasts must involve several cellular factors related to the fibroblast itself. Conclusions: These observations emphasize the importance of cultural conditions on the apparent radiosensitivity of human tumor cell lines, and suggest that the fibroblastic connective tissue enveloping the malignant cells should be considered when the aim is to establish a radiopredictive assay from surgical tumors fragments

Granulocyte macrophage colony stimulating factor (GM-CSF biological actions on human dermal fibroblasts

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S Montagnani

2009-12-01

Full Text Available Fibroblasts are involved in all pathologies characterized by increased ExtraCellularMatrix synthesis, from wound healing to fibrosis. Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF is a cytokine isolated as an hemopoietic growth factor but recently indicated as a differentiative agent on endothelial cells. In this work we demonstrated the expression of the receptor for GM-CSF (GMCSFR on human normal skin fibroblasts from healthy subjects (NFPC and on a human normal fibroblast cell line (NHDF and we try to investigate the biological effects of this cytokine. Human normal fibroblasts were cultured with different doses of GM-CSF to study the effects of this factor on GMCSFR expression, on cell proliferation and adhesion structures. In addition we studied the production of some Extra-Cellular Matrix (ECM components such as Fibronectin, Tenascin and Collagen I. The growth rate of fibroblasts from healthy donors (NFPC is not augmented by GM-CSF stimulation in spite of increased expression of the GM-CSFR. On the contrary, the proliferation of normal human dermal fibroblasts (NHDF cell line seems more influenced by high concentration of GM-CSF in the culture medium. The adhesion structures and the ECM components appear variously influenced by GM-CSF treatment as compared to fibroblasts cultured in basal condition, but newly only NHDF cells are really induced to increase their synthesis activity. We suggest that the in vitro treatment with GM-CSF can shift human normal fibroblasts towards a more differentiated state, due or accompanied by an increased expression of GM-CSFR and that such “differentiation” is an important event induced by such cytokine.

Synovial volume--a marker of disease severity in rheumatoid arthritis? Quantification by MRI

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Østergaard, Mikkel; Gideon, P; Henriksen, O

1994-01-01

Volumes of synovial membrane and joint effusion were determined by magnetic resonance imaging (MRI) in patients with inflammatory gonarthritis. Volumes were calculated by adding the outlined areas of synovium/effusion from a continuous series of gadolinium-DTPA-enhanced 5 mm transversal T1-weighted...

Radiation-Induced Differentiation in Human Lung Fibroblast

International Nuclear Information System (INIS)

Park, Sa-Rah; Ahn, Ji-Yeon; Han, Young-Soo; Shim, Jie-Young; Yun, Yeon-Sook; Song, Jie-Young

2007-01-01

One of the most common tumors in many countries is lung cancer and patients with lung cancer may take radiotherapy. Although radiotherapy may have its own advantages, it can also induce serious problems such as acute radiation pneumonitis and pulmonary fibrosis. Pulmonary fibrosis is characterized by excessive production of α-SMA and accumulation of extracellular matrix (ECM) such as collagen and fibronectin. There has been a great amount of research about fibrosis but the exact mechanism causing the reaction is not elucidated especially in radiation-induced fibrosis. Until now it has been known that several factors such as transforming growth factor (TGF-β), tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) are related to fibrosis. Among them TGF-β with Smad signaling is known to be the main stream and other signaling molecules such as MAPK, ERK and JNK (3) also participates in the process. In addition to those above factors, it is thought that more diverse and complicate mechanisms may involve in the radiationinduced fibrosis. Therefore, to investigate the underlying mechanisms in radiation induced fibrosis, first of all, we confirmed whether radiation induces trans differentiation in human normal lung fibroblasts. Here, we suggest that not only TGF-β but also radiation can induce trans differentiation in human lung fibroblast WI-38 and IMR-90

Collagen triple helix repeat containing 1 is a new promigratory marker of arthritic pannus.

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Shekhani, Mohammed Talha; Forde, Toni S; Adilbayeva, Altynai; Ramez, Mohamed; Myngbay, Askhat; Bexeitov, Yergali; Lindner, Volkhard; Adarichev, Vyacheslav A

2016-07-19

The formation of destructive hypercellular pannus is critical to joint damage in rheumatoid arthritis (RA). The collagen triple helix repeat containing 1 (CTHRC1) protein expressed by activated stromal cells of diverse origin has previously been implicated in tissue remodeling and carcinogenesis. We recently discovered that the synovial Cthrc1 mRNA directly correlates with arthritis severity in mice. This study characterizes the role of CTHRC1 in arthritic pannus formation. Synovial joints of mice with collagen antibody-induced arthritis (CAIA) and human RA-fibroblast-like synoviocytes (FLS) were immunostained for CTHRC1, FLS and macrophage-specific markers. CTHRC1 levels in plasma from patients with RA were measured using sandwich ELISA. The migratory response of fibroblasts was studied with a transwell migration assay and time-lapse microscopy. Velocity and directness of cell migration was analyzed by recording the trajectories of cells treated with rhCTHRC1. Immunohistochemical analysis of normal and inflamed synovium revealed highly inducible expression of CTHRC1 in arthritis (10.9-fold). At the tissue level, CTHRC1-expressing cells occupied the same niche as large fibroblast-like cells positive for α-smooth muscle actin (α-SMA) and cadherin 11 (CDH11). CTHRC1 was produced by activated FLS predominantly located at the synovial intimal lining and at the bone-pannus interface. Cultured RA-FLS expressed CDH11, α-SMA, and CTHRC1. Upon treatment with exogenous rhCTHRC1, embryonic fibroblasts and RA-FLS significantly increased migration velocity, directness, and cell length along the front-tail axis (1.4-fold, p pannus.

Anatomical Basis and Clinical Application of Synovial Flaps in the Wrist and Distal Forearm.

Science.gov (United States)

Colen, David L; Yeh, Jiun-Ting; Colen, Lawrence B

2017-05-01

Neuropathic symptoms after median nerve repair at the wrist or secondary to refractory carpal tunnel syndrome may become debilitating. These symptoms develop because of perineural adhesions, intraneural fibrosis, and fixation of the nerve to the transverse carpal ligament after surgery, and often require neurolysis. Interposition of vascularized soft tissue over the median nerve at the time of neurolysis prevents recurrence of such adhesions. The synovial flap, fashioned from the synovial lining of the flexor tendon sheath, is an ideal tissue for this purpose. Previous authors have described the surgical technique of the synovial flap, but the anatomical basis and design of the flap have not been previously discussed. Twenty fresh cadaver upper extremities were injected with Microfil to analyze the arterial anatomy, flap dimensions, and arc of rotation of the flexor tendon synovium mobilized as a flap suitable for coverage of the median nerve at the wrist. The authors determined that both radial and ulnar-based flaps are clinically useful for providing coverage in the wrist and distal forearm. This flap was used in 18 patients with complicated median nerve lesions in this region. All patients had an uncomplicated postoperative course. Of 13 patients treated for posttraumatic median nerve neuromas, all but two had significant resolution of symptoms. When used as a vascularized flap, the flexor tendon synovium provides adequate protection of the median nerve. Flap dimensions and vascularity of this tissue make it an ideal local flap option when performing reoperative surgery on the median nerve.

Synovial cysts of the lumbar spine; Cistos sinoviais lombares

Energy Technology Data Exchange (ETDEWEB)

Rosa, Ana Claudia Ferreira; Machado, Marcio Martins [Goias Univ., Goiania, GO (Brazil). Faculdade de Medicina. Hospital das Clinicas]. E-mail: anaclaudiaferreira@ig.com.br; Figueiredo, Marco Antonio Junqueira [Hospital Sirio-Libanes, Sao Paulo, SP (Brazil). Servico de Tomografia Computadorizada; Cerri, Giovanni Guido [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Dept. de Radiologia

2002-10-01

Intraspinal synovial cysts of the lumbar spine are rare and commonly associated with osteoarthritis of the facet joints, particularly at level L4-L5. Symptoms are uncommon and may include low-back pain or sciatica. These cysts are accurately diagnosed by using computed tomography and magnetic resonance imaging. Diagnosis is essential for the correct management of the cysts. Several treatment options are available including rest and immobilization, computed tomography guided corticosteroid injection, and surgery in patients that are nonresponsive to other treatment methods. (author)

Fibroblast growth factor receptor mediates fibroblast-dependent growth in EMMPRIN-depleted head and neck cancer tumor cells.

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Liu, Zhiyong; Hartman, Yolanda E; Warram, Jason M; Knowles, Joseph A; Sweeny, Larissa; Zhou, Tong; Rosenthal, Eben L

2011-08-01

Head and neck squamous cell carcinoma tumors (HNSCC) contain a dense fibrous stroma which is known to promote tumor growth, although the mechanism of stroma-mediated growth remains unclear. As dysplastic mucosal epithelium progresses to cancer, there is incremental overexpression of extracellular matrix metalloprotease inducer (EMMPRIN) which is associated with tumor growth and metastasis. Here, we present evidence that gain of EMMPRIN expression allows tumor growth to be less dependent on fibroblasts by modulating fibroblast growth factor receptor-2 (FGFR2) signaling. We show that silencing EMMPRIN in FaDu and SCC-5 HNSCC cell lines inhibits cell growth, but when EMMPRIN-silenced tumor cells were cocultured with fibroblasts or inoculated with fibroblasts into severe combined immunodeficient mice, the growth inhibition by silencing EMMPRIN was blunted by the presence of fibroblasts. Coculture experiments showed fibroblast-dependent tumor cell growth occurred via a paracrine signaling. Analysis of tumor gene expression revealed expression of FGFR2 was inversely related to EMMPRIN expression. To determine the role of FGFR2 signaling in EMMPRIN-silenced tumor cells, ligands and inhibitors of FGFR2 were assessed. Both FGF1 and FGF2 enhanced tumor growth in EMMPRIN-silenced cells compared with control vector-transfected cells, whereas inhibition of FGFR2 with blocking antibody or with a synthetic inhibitor (PD173074) inhibited tumor cell growth in fibroblast coculture, suggesting the importance of FGFR2 signaling in fibroblast-mediated tumor growth. Analysis of xenografted tumors revealed that EMMPRIN-silenced tumors had a larger stromal compartment compared with control. Taken together, these results suggest that EMMPRIN acquired during tumor progression promotes fibroblast-independent tumor growth.

Fibroblast growth factor receptor mediates fibroblast-dependent growth in EMMPRIN depleted head and neck cancer tumor cells

Science.gov (United States)

Liu, Zhiyong; Hartman, Yolanda E.; Warram, Jason M.; Knowles, Joseph A.; Sweeny, Larrisa; Zhou, Tong; Rosenthal, Eben L.

2011-01-01

Head and neck squamous cell carcinoma tumors (HNSCC) contain a dense fibrous stroma which is known to promote tumor growth, although the mechanism of stroma mediated growth remains unclear. As dysplastic mucosal epithelium progresses to cancer there is incremental overexpression of extracellular matrix metalloprotease inducer (EMMPRIN) which is associated with tumor growth and metastasis. Here we present evidence that gain of EMMPRIN expression allows tumor growth to be less dependent on fibroblasts by modulating fibroblast growth factor receptor-2 (FGFR2) signaling. We show that silencing EMMPRIN in FaDu and SCC-5 HNSCC cell lines inhibits cell growth, but when EMMPRIN-silenced tumor cells were co-cultured with fibroblasts or inoculated with fibroblasts into SCID mice, the growth inhibition by silencing EMMPRIN was blunted by the presence of fibroblasts. Co-culture experiments demonstrated fibroblast-dependent tumor cell growth occurred via a paracrine signaling. Analysis of tumor gene expression revealed expression of FGFR2 was inversely related to EMMPRIN expression. To determine the role of FGFR2 signaling in EMMPRIN silenced tumor cells, ligands and inhibitors of FGFR2 were assessed. Both FGF1 and FGF2 enhanced tumor growth in EMMPRIN silenced cells compared to control vector transfected cells, while inhibition of FGFR2 with blocking antibody or with a synthetic inhibitor (PD173074) inhibited tumor cell growth in fibroblast co-culture, suggesting the importance of FGFR2 signaling in fibroblast mediated tumor growth. Analysis of xenografted tumors revealed EMMPRIN silenced tumors had a larger stromal compartment compared to control. Taken together, these results suggest that EMMPRIN acquired during tumor progression promotes fibroblast independent tumor growth. PMID:21665938

Synovial volume--a marker of disease severity in rheumatoid arthritis? Quantification by MRI

DEFF Research Database (Denmark)

Østergaard, Mikkel; Gideon, P; Henriksen, O

1994-01-01

MR-images. Ten knees with clinically active gonarthritis (CAG), 8 knees with clinically inactive gonarthritis (CIG) and 5 healthy controls (HC) were examined. The synovial volume of CAG-, CIG- and HC-knees were significantly different. The median volumes were 79 ml, 21 ml and 3 ml, respectively...

Short-term results after arthroscopic resection of synovial plicae in the radiohumeral joint

DEFF Research Database (Denmark)

Brahe Pedersen, Jens; Kristensen, Pia Kjær; Mønsted, Peter

2017-01-01

INTRODUCTION: Painful Synovial Plicae (SP) in the posterolateral corner of the radiohumeral joint may be confused with lateral epicondylitis. The SP may impinge between the radial head and the humeral capitellum causing pain and snapping. The aim of this study was to evaluate the short-term results...

Clinical, epidemiological and endoscopic characteristics of the synovial plica in patients with arthroscopy

International Nuclear Information System (INIS)

Caliste Manzano, Osvaldo; Morasen Cuevas, Ricardo; Fresneda Labori, Ramon; Matamoros Rodriguez, Adis

2011-01-01

A prospective study of patients with surgical treatment of the knee through arthroscopy was carried out at the Rheumatology Service, belonging to 'Saturnino Lora' Teaching Clinical Surgical Provincial Hospital from Santiago de Cuba during the years 2000-2009; a decade in which 663 knees were surgically treated and, 208 due to a synovial plica. This last one turned out to be the most frequent disease, with predominance in the female sex and the ages from 16 to 25 years. There was a marked clinicoarthroscopic correspondence. Preoperative diagnosis consisted of lesion of the internal meniscus, chondromalacia patellae and synovitis, reason why they should be kept in mind as differential diagnosis in this syndrome. The way of healing the surgical section of the synovial plica is the cause of symptomatic relapse and surgical reintervention, as it happened in the patients of the case material 54,0 %, mainly attributable to fibrosis in the wound area.(author)

Preclinical Evidence of Anti-Tumor Activity Induced by EZH2 Inhibition in Human Models of Synovial Sarcoma.

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Satoshi Kawano

Full Text Available The catalytic activities of covalent and ATP-dependent chromatin remodeling are central to regulating the conformational state of chromatin and the resultant transcriptional output. The enzymes that catalyze these activities are often contained within multiprotein complexes in nature. Two such multiprotein complexes, the polycomb repressive complex 2 (PRC2 methyltransferase and the SWItch/Sucrose Non-Fermentable (SWI/SNF chromatin remodeler have been reported to act in opposition to each other during development and homeostasis. An imbalance in their activities induced by mutations/deletions in complex members (e.g. SMARCB1 has been suggested to be a pathogenic mechanism in certain human cancers. Here we show that preclinical models of synovial sarcoma-a cancer characterized by functional SMARCB1 loss via its displacement from the SWI/SNF complex through the pathognomonic SS18-SSX fusion protein-display sensitivity to pharmacologic inhibition of EZH2, the catalytic subunit of PRC2. Treatment with tazemetostat, a clinical-stage, selective and orally bioavailable small-molecule inhibitor of EZH2 enzymatic activity reverses a subset of synovial sarcoma gene expression and results in concentration-dependent cell growth inhibition and cell death specifically in SS18-SSX fusion-positive cells in vitro. Treatment of mice bearing either a cell line or two patient-derived xenograft models of synovial sarcoma leads to dose-dependent tumor growth inhibition with correlative inhibition of trimethylation levels of the EZH2-specific substrate, lysine 27 on histone H3. These data demonstrate a dependency of SS18-SSX-positive, SMARCB1-deficient synovial sarcomas on EZH2 enzymatic activity and suggests the potential utility of EZH2-targeted drugs in these genetically defined cancers.

Measurement of cytokine and adhesion molecule expression in synovial tissue by digital image analysis

NARCIS (Netherlands)

Kraan, M. C.; Smith, M. D.; Weedon, H.; Ahern, M. J.; Breedveld, F. C.; Tak, P. P.

2001-01-01

Digital image analysis (DIA) offers the opportunity to quantify the stained area and staining intensity when synovial tissue (ST) is investigated by immunohistochemical analysis. This study aimed at determining the sensitivity of DIA compared with semiquantitative analysis (SQA). Paired ST samples

Excessive Cellular Proliferation Negatively Impacts Reprogramming Efficiency of Human Fibroblasts.

Science.gov (United States)

Gupta, Manoj K; Teo, Adrian Kee Keong; Rao, Tata Nageswara; Bhatt, Shweta; Kleinridders, Andre; Shirakawa, Jun; Takatani, Tomozumi; Hu, Jiang; De Jesus, Dario F; Windmueller, Rebecca; Wagers, Amy J; Kulkarni, Rohit N

2015-10-01

The impact of somatic cell proliferation rate on induction of pluripotent stem cells remains controversial. Herein, we report that rapid proliferation of human somatic fibroblasts is detrimental to reprogramming efficiency when reprogrammed using a lentiviral vector expressing OCT4, SOX2, KLF4, and cMYC in insulin-rich defined medium. Human fibroblasts grown in this medium showed higher proliferation, enhanced expression of insulin signaling and cell cycle genes, and a switch from glycolytic to oxidative phosphorylation metabolism, but they displayed poor reprogramming efficiency compared with cells grown in normal medium. Thus, in contrast to previous studies, our work reveals an inverse correlation between the proliferation rate of somatic cells and reprogramming efficiency, and also suggests that upregulation of proteins in the growth factor signaling pathway limits the ability to induce pluripotency in human somatic fibroblasts. The efficiency with which human cells can be reprogrammed is of interest to stem cell biology. In this study, human fibroblasts cultured in media containing different concentrations of growth factors such as insulin and insulin-like growth factor-1 exhibited variable abilities to proliferate, with consequences on pluripotency. This occurred in part because of changes in the expression of proteins involved in the growth factor signaling pathway, glycolysis, and oxidative phosphorylation. These findings have implications for efficient reprogramming of human cells. ©AlphaMed Press.

Synovial Sarcoma of the Palatine Tonsil:Report of Two Cases and Review of theLiterature

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Negar Azarpira

2010-07-01

Full Text Available Here, we describe young men with synovial sarcoma in the palatine tonsil, who presented with a 3-4 month history of progressive sore throat, tonsillar ulcerativemass and bleeding. Clinical and radiological examinations revealed that the tumors arose from the palatine tonsil and extended to the parapharyngeal space. Both tumors were too advanced to remove completely; therefore, they underwent surgical debulking during tonsillectomy and partial pharyngectomy. Histopathological and immunohistochem-ical studies confirmed the diagnosis of synovial sarcoma of the palatine tonsil. Despite postoperative radiotherapy and systemic chemotherapy, they relapsed 18 and 22 months later. The first patient died from unresectable local recurrent disease three years after primary diagnosis, and the second patient is alive after 36 months, but suffers from unresectable locoregional recurrent disease and is receiving palliative chemotherapy and supportive care.

Replacement of murine fibroblasts by human fibroblasts irradiated in obtaining feeder layer for the culture of human keratinocytes

International Nuclear Information System (INIS)

Yoshito, Daniele; Sufi, Bianca S.; Santin, Stefany P.; Mathor, Monica B.; Altran, Silvana C.; Isaac, Cesar

2011-01-01

Human autologous epithelia cultivated in vitro, have been used successfully in treating damage to skin integrity. The methodology allowed the cultivation of these epithelia was described by Rheinwald and Green in 1975, this methodology consisted in seeding keratinocytes onto a feeder layer composed of lineage 3T3 murine fibroblasts, the proliferation rate is controlled through the action of ionizing radiation. However, currently there is a growing concern about the possibility of transmitting prions and murine viruses to transplanted patients. Taking into account this concern, in this present work, we replaced the feeder layer originally composed of murine fibroblasts by human fibroblasts. To obtain this new feeder layer was necessary to standardize the enough irradiation dose to inhibit the replication of human fibroblasts and the verification of effectiveness of the development of keratinocytes culture on a feeder layer thus obtained. According to the obtained results we can verify that the human fibroblasts irradiated at various tested doses (60, 70, 100, 200, 250 and 300 Gy) had their mitotic activity inactivated by irradiation, allowing the use of any of these doses to confection of the feeder layer, since these fibroblasts irradiated still showed viable until fourteen days of cultivation. In the test of colony formation efficiency was observed that keratinocytes seeded on irradiated human fibroblasts were able to develop satisfactorily, preserving their clonogenic potential. Therefore it was possible the replacement of murine fibroblasts by human fibroblasts in confection of the feeder layer, in order to eliminate this xenobiotic component of the keratinocytes culture. (author)

Replacement of murine fibroblasts by human fibroblasts irradiated in obtaining feeder layer for the culture of human keratinocytes

Energy Technology Data Exchange (ETDEWEB)

Yoshito, Daniele; Sufi, Bianca S.; Santin, Stefany P.; Mathor, Monica B. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Altran, Silvana C.; Isaac, Cesar [Universidade Sao Paulo (USP), Sao Paulo, SP (Brazil). Fac. de Medicina. Lab. de Microcirurgia Plastica; Esteves-Pedro, Natalia M. [Universidade Sao Paulo (USP), Sao Paulo, SP (Brazil). Fac. de Ciencias Farmaceuticas. Lab. de Controle Biologico; Herson, Marisa R. [DonorTissue Bank of Victoria (Australia)

2011-07-01

Human autologous epithelia cultivated in vitro, have been used successfully in treating damage to skin integrity. The methodology allowed the cultivation of these epithelia was described by Rheinwald and Green in 1975, this methodology consisted in seeding keratinocytes onto a feeder layer composed of lineage 3T3 murine fibroblasts, the proliferation rate is controlled through the action of ionizing radiation. However, currently there is a growing concern about the possibility of transmitting prions and murine viruses to transplanted patients. Taking into account this concern, in this present work, we replaced the feeder layer originally composed of murine fibroblasts by human fibroblasts. To obtain this new feeder layer was necessary to standardize the enough irradiation dose to inhibit the replication of human fibroblasts and the verification of effectiveness of the development of keratinocytes culture on a feeder layer thus obtained. According to the obtained results we can verify that the human fibroblasts irradiated at various tested doses (60, 70, 100, 200, 250 and 300 Gy) had their mitotic activity inactivated by irradiation, allowing the use of any of these doses to confection of the feeder layer, since these fibroblasts irradiated still showed viable until fourteen days of cultivation. In the test of colony formation efficiency was observed that keratinocytes seeded on irradiated human fibroblasts were able to develop satisfactorily, preserving their clonogenic potential. Therefore it was possible the replacement of murine fibroblasts by human fibroblasts in confection of the feeder layer, in order to eliminate this xenobiotic component of the keratinocytes culture. (author)

Platelet lysate enhances synovial fluid multipotential stromal cells functions: Implications for therapeutic use.

Science.gov (United States)

Altaie, Ala; Baboolal, Thomas G; Wall, Owen; Jones, Elena; McGonagle, Dennis

2018-03-01

Although intra-articular injection of platelet products is increasingly used for joint regenerative approaches, there are few data on their biological effects on joint-resident multipotential stromal cells (MSCs), which are directly exposed to the effects of these therapeutic strategies. Therefore, this study investigated the effect of platelet lysate (PL) on synovial fluid-derived MSCs (SF-MSCs), which in vivo have direct access to sites of cartilage injury. SF-MSCs were obtained during knee arthroscopic procedures (N = 7). Colony forming unit-fibroblast (CFU-F), flow-cytometric phenotyping, carboxyfluorescein succinimidyl ester-based immunomodulation for T-cell and trilineage differentiation assays were performed using PL and compared with standard conditions. PL-enhanced SF-MSC (PL-MSC) proliferation as CFU-F colonies was 1.4-fold larger, and growing cultures had shorter population-doubling times. PL-MSCs and fetal calf serum (FCS)-MSCs had the same immunophenotype and similar immunomodulation activities. In chondrogenic and osteogenic differentiation assays, PL-MSCs produced 10% more sulfated-glycosaminoglycan (sGAG) and 45% less Ca ++ compared with FCS-MSCs, respectively. Replacing chondrogenic medium transforming growth factor-β3 with 20% or 50% PL further increased sGAG production of PL-MSCs by 69% and 95%, respectively, compared with complete chondrogenic medium. Also, Dulbecco's Modified Eagle's Medium high glucose (HG-DMEM) plus 50% PL induced more chondrogenesis compared with HG-DMEM plus 10% FCS and was comparable to complete chondrogenic medium. This is the first study to assess SF-MSC responses to PL and provides biological support to the hypothesis that PL may be capable of modulating multiple functional aspects of joint resident MSCs with direct access to injured cartilage. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Clues to pathogenesis of spondyloarthropathy derived from synovial fluid mononuclear cell gene expression profiles

NARCIS (Netherlands)

Gu, Jieruo; Rihl, Markus; Märker-Hermann, Elisabeth; Baeten, Dominique; Kuipers, Jens G.; Song, Yeong Wook; Maksymowych, Walter P.; Burgos-Vargas, Ruben; Veys, Eric M.; de Keyser, Filip; Deister, Helmuth; Xiong, Momiao; Huang, Feng; Tsai, Wen Chan; Yu, David Tak Yan

2002-01-01

OBJECTIVE: To use gene expression profiles of spondyloarthropathy (SpA) synovial fluid mononuclear cells (SFMC) to determine if there are transcripts that support the unfolded protein response (UPR) hypothesis, and to identify which cytokines/chemokines are being expressed and which cell fractions

Interleukin-1 alpha modulates collagen gene expression in cultured synovial cells.

Science.gov (United States)

Mauviel, A; Teyton, L; Bhatnagar, R; Penfornis, H; Laurent, M; Hartmann, D; Bonaventure, J; Loyau, G; Saklatvala, J; Pujol, J P

1988-01-01

The effects of porcine interleukin-1 (IL-1) alpha on collagen production were studied in cultured human rheumatoid synovial cells. Addition of 0.05-5 ng of IL-1/ml into the cultures resulted in a dose-dependent decreased rate of collagen released into the medium over 24 h. To determine whether this inhibition was due to secondary action of prostaglandin E2 (PGE2) secreted in response to IL-1, cultures were incubated in presence of various inhibitors of arachidonate metabolism. Depending on the cell strains, these inhibitors were able to suppress or diminish the effect of IL-1, suggesting that PGE2 is involved in the mechanism. Depression of collagen production caused by IL-1 mainly affected type I collagen and therefore led to a change in the type I/type III collagen ratio in the extracellular medium. Steady-state levels of mRNA for types I and III procollagens were estimated by dot-blot hybridization and compared with the amounts of respective collagens produced in the same cultures. IL-1 generally increased procollagen type I mRNA, but to a variable extent, as did indomethacin (Indo). Depending on the cell strain, the combination of indo and IL-1 could elevate the mRNA level of type I procollagen compared with Indo alone. These results did not correlate with the production rate of collagen in the medium, which was diminished by exposure to IL-1. The level of mRNA for collagen type III was not greatly changed by incubation with IL-1, and a better correlation was generally observed with the amount of type III collagen found in the medium. These data suggest that an additional control mechanism at translational or post-translational level must exist, counterbalancing the stimulatory effect of IL-1 on collagen mRNA transcription. It is likely that IL-1 could modulate the production of collagen in synovial cells by an interplay of different mechanisms, some of them limiting the effect of primary elevation of the steady-state mRNA level. Images Fig. 3. Fig. 4. Fig. 5

A novel role of EMMPRIN/CD147 in transformation of quiescent fibroblasts to cancer-associated fibroblasts by breast cancer cells

Science.gov (United States)

Xu, Jing; Lu, Yang; Qiu, Songbo; Chen, Zhi-Nan; Fan, Zhen

2013-01-01

We tested the novel hypothesis that EMMPRIN/CD147, a transmembrane glycoprotein overexpressed in breast cancer cells, has a previously unknown role in transforming fibroblasts to cancer-associated fibroblasts, and that cancer-associated fibroblasts in turn induce epithelial-to-mesenchymal transition of breast cancer cells. Co-culture of fibroblasts with breast cancer cells or treatment of fibroblasts with breast cancer cell conditioned culture medium or recombinant EMMPRIN/CD147 induced expression of α-SMA in the fibroblasts in an EMMPRIN/CD147-dependent manner and promoted epithelial-to-mesenchymal transition of breast cancer cells and enhanced cell migration potential. These findings support a novel role of EMMPRIN/CD147 in regulating the interaction between cancer and stroma. PMID:23474495

Condromatosis sinovial de la articulación temporomandibular con extensión a la base de cráneo Synovial chondromatosis of the temporomandibular joint. A rare case with subcranial extension

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Ana Belén Marín Fernández

2013-03-01

Full Text Available La condromatosis sinovial (CS es una metaplasia cartilaginosa de los remanentes mesenquimales del tejido sinovial de las articulaciones. Es una enfermedad de etiología desconocida y poco frecuente. Puede definirse como un proceso benigno sinovial caracterizado por la formación de nódulos cartilaginosos (cuerpos libres. La CS afecta principalmente a grandes articulaciones sinoviales siendo poco común su aparición en la articulación temporomandibular. La sintomatología predominante es dolor, inflamación, limitación de los movimientos mandibulares, crepitación y laterodesviación mandibular. El diagnóstico se realiza mediante el estudio radiológico y artroscópico de la articulación. El tratamiento adecuado englobaría la extirpación completa de los cuerpos libres y de la sinovial afecta, bien mediante artroscopia o mediante cirugía abierta. Cuando está afectada la articulación temporomandibular las lesiones suelen estar localizadas en la cavidad articular, siendo rara su extensión extraarticular. En este artículo describimos un caso excepcional de condromatosis sinovial con extensión a la fosa craneal media.Synovial chondromatosis (SC is a cartilaginous metaplasia of the mesenchymal remnants of the synovial tissue of joints. It is an uncommon disease of unknown origin. This benign synovial process involves the formation of cartilaginous nodules (loose bodies in the synovium and within the articular space. SC mainly affects large synovial joints, and only very rarely affects the temporomandibular joint (TMJ. The main symptoms are pain, swelling, mouth opening limitation, crepitation, and lateral mandibular deviation. Diagnosis can be made by panoramic radiograph, computed tomography scan, magnetic resonance imaging, and arthroscopy of the TMJ. The main treatment includes complete removal of the loose bodies in conjunction with excision of the affected synovium. It can be performed by arthroscopy or by open surgery. In cases with

Primary pleuropulmonary synovial sarcoma with brain metastases in a paediatric patient: an unusual presentation.

Science.gov (United States)

Chirmade, Pushpak Chandrakant; Parikh, Sonia; Anand, Asha; Panchal, Harsha; Patel, Apurva; Shah, Sandip

2017-01-01

Primary lung neoplasms are rare in children. The most common primary lung malignancies in children are pleuropulmonary blastoma and carcinoid tumour. Synovial sarcoma (SS) accounts for approximately 1% of all childhood malignancies. In absolute terms, the SS of the lungs and pleura are extremely rare and pose a diagnostic difficulty. Soft tissue sarcomas usually have a high potential for metastases, however, metastasis to the brain is rare, even in widely disseminated disease, and it has been described only in 3 case reports previously. Primary pleuropulmonary SS with brain metastases is even rarer. Here we present a case of an 11-year-old boy who presented with respiratory complaints, viz. fever and cough for 20 days. Initial impression was lung abscess, however, on histopathological, immunohistochemical and molecular study, the disorder was diagnosed as synovial sarcoma. After a week from the first consult, the child developed neurological symptoms, viz., an episode of convulsion and gradually worsening power of the lower limb. Computed tomography scan and Magnetic Resonance Spectroscopy was suggestive of brain metastases. Given the rarity of primary lung neoplasms in children, clinical detection remains a challenge. Delayed diagnoses are common as respiratory symptoms may be attributed to inflammatory or infective processes. Primary pleuropulmonary synovial sarcoma is a rare tumour and it is not known to commonly metastasise to the brain. Though rare, primary pleuropulmonary SS should be considered an important differential among peadiatric primary lung neoplasms due to its potential for curability if detected early, and more aggressive metastatic pattern, e.g. brain metastases making early detection imperative.

Cultured human foreskin fibroblasts produce a factor that stimulates their growth with properties similar to basic fibroblast growth factor

International Nuclear Information System (INIS)

Story, M.T.

1989-01-01

To determine if fibroblasts could be a source of fibroblast growth factor (FGF) in tissue, cells were initiated in culture from newborn human foreskin. Fibroblast cell lysates promoted radiolabeled thymidine uptake by cultured quiescent fibroblasts. Seventy-nine percent of the growth-promoting activity of lysates was recovered from heparin-Sepharose. The heparin-binding growth factor reacted on immunoblots with antiserum to human placenta-derived basic FGF and competed with iodinated basic FGF for binding to antiserum to (1-24)bFGF synthetic peptide. To confirm that fibroblasts were the source of the growth factor, cell lysates were prepared from cells incubated with radiolabeled methionine. Heparin affinity purified material was immunoprecipitated with basic FGF antiserum and electrophoresed. Radiolabeled material was detected on gel autoradiographs in the same molecular weight region as authentic iodinated basic FGF. The findings are consistant with the notion that cultured fibroblasts express basic FGF. As these cells also respond to the mitogen, it is possible that the regulation of their growth is under autocrine control. Fibroblasts may be an important source of the growth factor in tissue

Tumor-produced, active Interleukin-1 β regulates gene expression in carcinoma-associated fibroblasts

International Nuclear Information System (INIS)

Dudas, Jozsef; Fullar, Alexandra; Bitsche, Mario; Schartinger, Volker; Kovalszky, Ilona; Sprinzl, Georg Mathias; Riechelmann, Herbert

2011-01-01

Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1β (IL1-β) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-β expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-β processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated with IL1-β. IL1-β signaling was investigated by western blot and immunocytochemistry. IL1-β-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-β, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NFκBα. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-β reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved by DEX inhibition for IL1-β-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-β in the tumor cells leads to IL1-β-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-β. PDL fibroblasts possess receptor for IL1-β, and its expression is increased 4.56-times in the presence of SCC-25 tumor cells. IL1-β receptor expression in

Tumor-produced, active Interleukin-1 {beta} regulates gene expression in carcinoma-associated fibroblasts

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Dudas, Jozsef, E-mail: Jozsef.Dudas@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Fullar, Alexandra, E-mail: fullarsz@gmail.com [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary); Bitsche, Mario, E-mail: Mario.Bitsche@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Schartinger, Volker, E-mail: Volker.Schartinger@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Kovalszky, Ilona, E-mail: koval@korb1.sote.hu [1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest (Hungary); Sprinzl, Georg Mathias, E-mail: Georg.Sprinzl@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria); Riechelmann, Herbert, E-mail: Herbert.Riechelmann@i-med.ac.at [Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck (Austria)

2011-09-10

Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1{beta} (IL1-{beta}) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-{beta} expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-{beta} processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated with IL1-{beta}. IL1-{beta} signaling was investigated by western blot and immunocytochemistry. IL1-{beta}-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-{beta}, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NF{kappa}B{alpha}. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-{beta} reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved by DEX inhibition for IL1-{beta}-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-{beta} in the tumor cells leads to IL1-{beta}-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-{beta}. PDL fibroblasts possess receptor for IL1-{beta}, and its expression is increased 4.56-times in the

Cortactin involvement in the keratinocyte growth factor and fibroblast growth factor 10 promotion of migration and cortical actin assembly in human keratinocytes

International Nuclear Information System (INIS)

Ceccarelli, Simona; Cardinali, Giorgia; Aspite, Nicaela; Picardo, Mauro; Marchese, Cinzia; Torrisi, Maria Rosaria; Mancini, Patrizia

2007-01-01

Keratinocyte growth factor (KGF/FGF7) and fibroblast growth factor 10 (FGF10/KGF2) regulate keratinocyte proliferation and differentiation by binding to the tyrosine kinase KGF receptor (KGFR). KGF induces keratinocyte motility and cytoskeletal rearrangement, whereas a direct role of FGF10 on keratinocyte migration is not clearly established. Here we analyzed the motogenic activity of FGF10 and KGF on human keratinocytes. Migration assays and immunofluorescence of actin cytoskeleton revealed that FGF10 is less efficient than KGF in promoting migration and exerts a delayed effect in inducing lamellipodia and ruffles formation. Both growth factors promoted phosphorylation and subsequent membrane translocation of cortactin, an F-actin binding protein involved in cell migration; however, FGF10-induced cortactin phosphorylation was reduced, more transient and delayed with respect to that promoted by KGF. Cortactin phosphorylation induced by both growth factors was Src-dependent, while its membrane translocation and cell migration were blocked by either Src and PI3K inhibitors, suggesting that both pathways are involved in KGF- and FGF10-dependent motility. Furthermore, siRNA-mediated downregulation of cortactin inhibited KGF- and FGF10-induced migration. These results indicate that cortactin is involved in keratinocyte migration promoted by both KGF and FGF10

Involvement of interleukin-8 in dialysis-related arthritis.

Science.gov (United States)

Takayama, F; Miyazaki, T; Aoyama, I; Tsukushi, S; Sato, M; Yamazaki, C; Shimokata, K; Niwa, T

1998-04-01

To elucidate the role of interleukin (IL)-8, a chemotactic factor for neutrophils, in dialysis-related arthritis (DRA) of patients on long-term hemodialysis, the concentration of IL-8 was measured in the synovial fluids of DRA patients with acute arthralgia and joint swelling, and was compared with those in patients with rheumatoid arthritis (RA) and patients with osteoarthritis (OA). We noted a marked elevation of IL-8 in the joint fluids of patients with DRA and RA as compared with OA. Furthermore, to determine the role of IL-8 in synovitis, we examined the in vivo effect of intra-articular injection of human recombinant IL-8 on leukocyte infiltration into the joint space of rabbits. A single injection of IL-8 to the joints of rabbits induced rapid infiltration of neutrophils into the joint space and synovial tissues, which reached a maximum in four hours. The oral administration of indometacin farnesil (a prodrug that is converted to indomethacin after intestinal absorption) before the injection of IL-8 alleviated the infiltration of neutrophils. When human synovial cells were incubated with tumor necrosis factor (TNF)-alpha, the expression of IL-8 mRNA and IL-8 production in the cultured synovial cells were increased. The TNF-alpha-stimulated expression of IL-8 mRNA and IL-8 production in the cultured synovial cells were markedly inhibited by dexamethasone. In conclusion, IL-8 levels were markedly elevated in the joint fluids of patients with DRA. Interleukin-8 released from synovial cells may be an important factor to induce acute inflammation in DRA. Dexamethasone and indomethacin may be effective for DRA by inhibiting the production and chemotactic actions of IL-8, respectively.

High-sensitivity virus and mycoplasma screening test reveals high prevalence of parvovirus B19 infection in human synovial tissues and bone marrow.

Science.gov (United States)

Watanabe, Ken; Otabe, Koji; Shimizu, Norio; Komori, Keiichirou; Mizuno, Mitsuru; Katano, Hisako; Koga, Hideyuki; Sekiya, Ichiro

2018-03-27

Latent microorganism infection is a safety concern for the clinical application of mesenchymal stem cells (MSCs). The aim of this study is to investigate the frequencies and sensitivities of the latent virus and mycoplasma infections in synovium, bone marrow, peripheral blood cells, and blood plasma and cultured synovial MSCs. Total DNA and RNA of the synovium (n = 124), bone marrow (n = 123), peripheral blood cells (n = 121), plasma (n = 121), and 14-day cultured synovial MSCs (n = 63) were collected from patients who underwent total knee arthroplasty or anterior ligament reconstruction after written informed consents were obtained. The multiplex polymerase chain reaction (PCR) primers were designed to quantitatively measure the representative genomes of 13 DNA viruses, 6 RNA viruses, and 9 mycoplasmas. Multi-spliced mRNA detection and virus spike test were also performed to demonstrate the sensitivity of synovial MSCs to the candidate pathogens. In synovium and bone marrow, the positive rates of parvovirus B19 genome were significantly higher than in peripheral blood cells (18.7% and 22% vs. 0.8%, respectively). Multi-alignment analysis of amplified and sequenced viral target genes showed the proximity of the parvovirus B19 gene from different tissue in the same patients. Synovial MSCs cultured for 14 days were positive for virus infection only in two patients (2/62 = 3%). Parvovirus B19 multi-spliced mRNAs were not detected in these two samples. Virus spike test demonstrated the sensitivity of synovial MSCs to herpes simplex virus (HSV)1 and cytomegalovirus (CMV), but not to parvovirus B19. This study revealed a relatively high incidence of latent parvovirus B19 in synovium and bone marrow tissue.

Fibroblast cultures in duchenne muscular dystrophy

International Nuclear Information System (INIS)

Ionasescu, V.; Lara-Braud, C.; Zellweger, H.; Ionasescu, R.; Burmeister, L.

1977-01-01

Primary skin fibroblast cultures were grown from forearm pinch skin biopsies obtained from 24 patients with Duchenne muscular dystrophy (DMD) and ten normal controls matched for sex and age. The first subcultures were grown for 7 days and incubated with L-( 3 H)-proline for 24 hours. Intracellular collagen incoption was significantly decreased (2.2 X) and extracellular collagen incorporation significantly increased (1.8 X) in fibroblast cultures from patients with DMD by both collagenase assay and polyacrylamide gel electrophoresis. The synthesis of noncollagen proteins showed low values from the DMD fibroblast cultures. The alterations in synthesis and secretion of collagen and noncollagen proteins were characteristic only for the log phase of DMD fibroblasts. (author)

Inhibitory Effect of Curcumol on Jak2-STAT Signal Pathway Molecules of Fibroblast-Like Synoviocytes in Patients with Rheumatoid Arthritis

Directory of Open Access Journals (Sweden)

Heng Wang

2012-01-01

Full Text Available Hyperplasia of synovial membrane in rheumatoid arthritis (RA is a critical pathological foundation for inducing articular injury. The janus kinase and signal transducer and activator of transcription (Jak-STAT pathway plays a critical role in synovial membrane proliferation induced by platelet-derived growth factor (PDGF. To explore the anti-cell proliferation mechanism of curcumol, a pure monomer extracted from Chinese medical plant zedoary rhizome, the changes of Jak2-STAT1/3 signal pathway-related molecules in synoviocytes were observed in vitro. In this study, the fibroblast-like synoviocytes (FLS in patients with RA were collected and cultured. The following parameters were measured: cell proliferation (WST-1 assay, cell cycles (fluorescence-activated cell sorting, FACS, STAT1 and STAT3 activities (electrophoretic mobility shift assay, EMSA, and the protein expressions of phosphorylated Jak2, STAT1, and STAT3 (Western blot. It was shown that curcumol could inhibit the RA-FLS proliferation and DNA synthesis induced by PDGF-BB in a dose-dependent manner in vitro. The transcription factors activities of STAT1 and STAT3 were obviously elevated after PDGF-BB stimulation (P<0.05. Super-shift experiments identified the STAT1 or STAT3 proteins in the complex. Furthermore, the different concentration curcumol could downregulate the DNA binding activities of STAT1 and STAT3 (P<0.05 and inhibit the phosphorylation of Jak2 while it had no effect on the protein expressions of STAT1 and STAT3. Positive correlations were found between changes of cell proliferation and DNA-binding activities of STAT1 and STAT3, respectively (P<0.01. In conclusion, curcumol might suppress the FLS proliferation and DNA synthesis induced by PDGF-BB through attenuating Jak2 phosphorylation, downregulating STAT1 and STAT3 DNA-binding activities, which could provide theoretical foundation for clinical treatment of RA.

Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

International Nuclear Information System (INIS)

Li, D.X.; Deng, T.Z.; Lv, J.; Ke, J.

2014-01-01

Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction

Advanced glycation end products (AGEs) and their receptor (RAGE) induce apoptosis of periodontal ligament fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Li, D.X.; Deng, T.Z.; Lv, J.; Ke, J. [Department of Stomatology, Air Force General Hospital PLA, Haidian District, Beijing (China)

2014-09-19

Diabetics have an increased prevalence of periodontitis, and diabetes is one of the causative factors of severe periodontitis. Apoptosis is thought to be involved in this pathogenic relationship. The aim of this study was to investigate apoptosis in human periodontal ligament (PDL) fibroblasts induced by advanced glycation end products (AGEs) and their receptor (RAGE). We examined the roles of apoptosis, AGEs, and RAGE during periodontitis in diabetes mellitus using cultured PDL fibroblasts that were treated by AGE-modified bovine serum albumin (AGE-BSA), bovine serum albumin (BSA) alone, or given no treatment (control). Microscopy and real-time quantitative PCR indicated that PDL fibroblasts treated with AGE-BSA were deformed and expressed higher levels of RAGE and caspase 3. Cell viability assays and flow cytometry indicated that AGE-BSA reduced cell viability (69.80±5.50%, P<0.01) and increased apoptosis (11.31±1.73%, P<0.05). Hoechst 33258 staining and terminal-deoxynucleotidyl transferase-mediated nick-end labeling revealed that AGE-BSA significantly increased apoptosis of PDL fibroblasts. The results showed that the changes in PDL fibroblasts induced by AGE-BSA may explain how AGE-RAGE participates in and exacerbates periodontium destruction.

Estimation of low-dose radiation-responsive proteins in the absence of genomic instability in normal human fibroblast cells.

Science.gov (United States)

Yim, Ji-Hye; Yun, Jung Mi; Kim, Ji Young; Nam, Seon Young; Kim, Cha Soon

2017-11-01

Low-dose radiation has various biological effects such as adaptive responses, low-dose hypersensitivity, as well as beneficial effects. However, little is known about the particular proteins involved in these effects. Here, we sought to identify low-dose radiation-responsive phosphoproteins in normal fibroblast cells. We assessed genomic instability and proliferation of fibroblast cells after γ-irradiation by γ-H2AX foci and micronucleus formation analyses and BrdU incorporation assay, respectively. We screened fibroblast cells 8 h after low-dose (0.05 Gy) γ-irradiation using Phospho Explorer Antibody Microarray and validated two differentially expressed phosphoproteins using Western blotting. Cell proliferation proceeded normally in the absence of genomic instability after low-dose γ-irradiation. Phospho antibody microarray analysis and Western blotting revealed increased expression of two phosphoproteins, phospho-NFκB (Ser536) and phospho-P70S6K (Ser418), 8 h after low-dose radiation. Our findings suggest that low-dose radiation of normal fibroblast cells activates the expression of phospho-NFκB (Ser536) and phospho-P70S6K (Ser418) in the absence of genomic instability. Therefore, these proteins may be involved in DNA damage repair processes.

The fibroblast surface markers FAP, anti-fibroblast, and FSP are expressed by cells of epithelial origin and may be altered during epithelial-to-mesenchymal transition.

Science.gov (United States)

Kahounová, Zuzana; Kurfürstová, Daniela; Bouchal, Jan; Kharaishvili, Gvantsa; Navrátil, Jiří; Remšík, Ján; Šimečková, Šárka; Študent, Vladimír; Kozubík, Alois; Souček, Karel

2017-04-06

The identification of fibroblasts and cancer-associated fibroblasts from human cancer tissue using surface markers is difficult, especially because the markers used currently are usually not expressed solely by fibroblasts, and the identification of fibroblast-specific surface molecules is still under investigation. It was aimed to compare three commercially available antibodies in the detection of different surface epitopes of fibroblasts (anti-fibroblast, fibroblast activation protein α, and fibroblast surface protein). The specificity of their expression, employing fibroblast cell lines and tumor-derived fibroblasts from breast and prostate tissues was investigated. Both the established fibroblast cell line HFF-1 and ex vivo primary fibroblasts isolated from breast and prostate cancer tissues expressed the tested surface markers to different degrees. Surprisingly, those markers were expressed also by permanent cell lines of epithelial origin, both benign and cancer-derived (breast-cell lines MCF 10A, HMLE and prostate-cell lines BPH-1, DU 145, and PC-3). The expression of fibroblast activation protein α increased on the surface of previously described models of epithelial cells undergoing epithelial-to-mesenchymal transition in response to treatment with TGF-β1. To prove the co-expression of the fibroblast markers on cells of epithelial origin, we used freshly dissociated human prostate and breast cancer tissues. The results confirmed the co-expression of anti-fibroblast and fibroblast surface protein on CD31/CD45-negative/EpCAM-positive epithelial cells. In summary, our data support the findings that the tested fibroblast markers are not fibroblast specific and may be expressed also by cells of epithelial origin (e.g., cells undergoing EMT). Therefore, the expression of these markers should be interpreted with caution, and the combination of several epitopes for both positive (anti-fibroblast or fibroblast activation protein α) and negative (Ep

Demonstration of extracellular peptidylarginine deiminase (PAD) activity in synovial fluid of patients with rheumatoid arthritis using a novel assay for citrullination of fibrinogen

DEFF Research Database (Denmark)

Damgaard, Dres; Senolt, Ladislav; Nielsen, Michael Friberg

2014-01-01

INTRODUCTION: Members of the peptidylarginine deiminase (PAD) family catalyse the posttranslational conversion of peptidylarginine to peptidylcitrulline. Citrullination of proteins is well described in rheumatoid arthritis (RA), and hypercitrullination of proteins may be related to inflammation...... in general. PAD activity has been demonstrated in various cell lysates, but so far not in synovial fluid. We aimed to develop an assay for detection of PAD activity, if any, in synovial fluid from RA patients. METHODS: An enzyme-linked immunosorbent assay using human fibrinogen as the immobilized substrate...... for citrullination and anti-citrullinated fibrinogen antibody as the detecting agent were used for measurement of PAD activity in synovial fluid samples from five RA patients. The concentrations of PAD2 and calcium were also determined. RESULTS: Approximately 150 times lower levels of recombinant human PAD2 (rhPAD2...

A fibroblast-associated antigen: Characterization in fibroblasts and immunoreactivity in smooth muscle differentiated stromal cells

DEFF Research Database (Denmark)

Rønnov-Jessen, Lone; Celis, Julio E.; van Deurs, Bo

1992-01-01

major brands migrating at apparent Mr of 38,000, 45,000, and 80,000, in addition to many minor bands between Mr 45,000 and 97,000, including Mr 52,000. The Mr 45,000 and 38,000 were associated with the cell membrane and Mr 52,000 as well as Mr 38,000 were associated with the lysosomes. The 1B10......Fibroblasts with smooth muscle differentiation are frequently derived from human breast tissue. Immunofluorescence cytochemistry of a fibroblast-associated antigen recognized by a monoclonal antibody (MAb), 1B10, was analyzed with a view to discriminating smooth muscle differentiated fibroblasts...

Fibroblastic and myofibroblastic tumors of the head and neck: Comprehensive imaging-based review with pathologic correlation

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Hourani, Roula, E-mail: rh64@aub.edu.lb [Department of Diagnostic Radiology, American University of Beirut Medical Center, Beirut (Lebanon); Taslakian, Bedros, E-mail: bt05@aub.edu.lb [Department of Diagnostic Radiology, American University of Beirut Medical Center, Beirut (Lebanon); Shabb, Nina S., E-mail: ns04@aub.edu.lb [Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut (Lebanon); Nassar, Lara, E-mail: ln07@aub.edu.lb [Department of Diagnostic Radiology, American University of Beirut Medical Center, Beirut (Lebanon); Hourani, Mukbil H., E-mail: mh17@aub.edu.lb [Department of Diagnostic Radiology, American University of Beirut Medical Center, Beirut (Lebanon); Moukarbel, Roger, E-mail: rm17@aub.edu.lb [Department of Otolaryngology – Head and Neck Surgery, American University of Beirut Medical Center, Beirut (Lebanon); Sabri, Alain, E-mail: as71@aub.edu.lb [Department of Otolaryngology – Head and Neck Surgery, American University of Beirut Medical Center, Beirut (Lebanon); Rizk, Toni, E-mail: tonirisk@hotmail.com [Department of Neurosurgery, Hôtel-Dieu de France, Saint-Joseph University, Beirut (Lebanon)

2015-02-15

Highlights: • Almost all fibroblastic tumors are evaluated with non-invasive imaging. • Radiologists should be familiar with the imaging appearance of fibroblastic tumors. • Most appropriate initial examination when fibromatosis coli suspected is ultrasound. • Most common location of ossifying fibromas is the tooth-bearing regions. - Abstract: Fibroblastic and myofibroblastic tumors of the head and neck are a heterogeneous group of disorders characterized by the proliferation of fibroblasts, myofibroblasts, or both. These tumors may be further subclassified on the basis of their behavior as benign, intermediate with malignant potential, or malignant. There are different types of fibroblastic and myofibroblastic tumors that can involve the head and neck including desmoid-type fibromatosis, solitary fibrous tumor, myofibroma/myofibromatosis, nodular fasciitis, nasopharyngeal angiofibroma, fibrosarcoma, dermatofibrosarcoma protuberans, fibromatosis coli, inflammatory myofibroblastic tumor, ossifying fibroma, fibrous histiocytoma, nodular fasciitis, fibromyxoma, hyaline fibromatosis and fibrous hamartoma. Although the imaging characteristics of fibroblastic and myofibroblastic tumors of the head and neck are nonspecific, imaging plays a pivotal role in the noninvasive diagnosis and characterization of these tumors, providing information about the constitution of tumors, their extension and invasion of adjacent structures. Correlation with the clinical history may help limit the differential diagnosis and radiologists should be familiar with the imaging appearance of these tumors to reach an accurate diagnosis.

Fibroblastic and myofibroblastic tumors of the head and neck: Comprehensive imaging-based review with pathologic correlation

International Nuclear Information System (INIS)

Hourani, Roula; Taslakian, Bedros; Shabb, Nina S.; Nassar, Lara; Hourani, Mukbil H.; Moukarbel, Roger; Sabri, Alain; Rizk, Toni

2015-01-01

Highlights: • Almost all fibroblastic tumors are evaluated with non-invasive imaging. • Radiologists should be familiar with the imaging appearance of fibroblastic tumors. • Most appropriate initial examination when fibromatosis coli suspected is ultrasound. • Most common location of ossifying fibromas is the tooth-bearing regions. - Abstract: Fibroblastic and myofibroblastic tumors of the head and neck are a heterogeneous group of disorders characterized by the proliferation of fibroblasts, myofibroblasts, or both. These tumors may be further subclassified on the basis of their behavior as benign, intermediate with malignant potential, or malignant. There are different types of fibroblastic and myofibroblastic tumors that can involve the head and neck including desmoid-type fibromatosis, solitary fibrous tumor, myofibroma/myofibromatosis, nodular fasciitis, nasopharyngeal angiofibroma, fibrosarcoma, dermatofibrosarcoma protuberans, fibromatosis coli, inflammatory myofibroblastic tumor, ossifying fibroma, fibrous histiocytoma, nodular fasciitis, fibromyxoma, hyaline fibromatosis and fibrous hamartoma. Although the imaging characteristics of fibroblastic and myofibroblastic tumors of the head and neck are nonspecific, imaging plays a pivotal role in the noninvasive diagnosis and characterization of these tumors, providing information about the constitution of tumors, their extension and invasion of adjacent structures. Correlation with the clinical history may help limit the differential diagnosis and radiologists should be familiar with the imaging appearance of these tumors to reach an accurate diagnosis

Structure of rat acidic fibroblast growth factor at 1.4 A resolution

DEFF Research Database (Denmark)

Kulahin, Nikolaj; Kiselyov, Vladislav; Kochoyan, Artur

2007-01-01

Fibroblast growth factors (FGFs) constitute a family of 22 structurally related heparin-binding polypeptides that are involved in the regulation of cell growth, survival, differentiation and migration. Here, a 1.4 A resolution X-ray structure of rat FGF1 is presented. Two molecules are present...

Progranulin Overproduction Due to Fli-1 Deficiency Contributes to the Resistance of Dermal Fibroblasts to Tumor Necrosis Factor in Systemic Sclerosis.

Science.gov (United States)

Ichimura, Yohei; Asano, Yoshihide; Akamata, Kaname; Noda, Shinji; Taniguchi, Takashi; Takahashi, Takehiro; Toyama, Tetsuo; Tada, Yayoi; Sugaya, Makoto; Sato, Shinichi; Kadono, Takafumi

2015-12-01

Progranulin is a growth factor that is active in wound repair and is an antagonist of tumor necrosis factor (TNF) receptors, regulating fibroblast activation, angiogenesis, and inflammation. Because long-standing activation of gene programs related to wound healing is a hallmark of systemic sclerosis (SSc), we sought to investigate the role of progranulin in SSc. Progranulin expression levels in human and murine skin samples were determined by immunohistochemical analysis and quantitative reverse transcription-polymerase chain reaction. The role of progranulin in fibroblast activation was examined using a gene-silencing technique. Progranulin levels in serum obtained from 60 patients with SSc and 16 healthy control subjects were determined by enzyme-linked immunosorbent assay. Progranulin expression was increased in SSc dermal fibroblasts compared with normal dermal fibroblasts, both in vivo and in vitro. Transcription factor Fli-1, a deficiency of which is involved in the activation of SSc dermal fibroblasts, served as a potent repressor of the progranulin gene, and Fli-1(+/-) mice and bleomycin-treated wild-type mice exhibited up-regulated expression of progranulin in dermal fibroblasts. SSc dermal fibroblasts were resistant to the antifibrotic effect of TNF, but this resistance was reversed by gene silencing of progranulin. Serum progranulin levels were elevated in patients with early diffuse cutaneous SSc (dcSSc), especially in those with inflammatory skin symptoms, and were positively correlated with the C-reactive protein level. Progranulin overproduction due to Fli-1 deficiency may contribute to the constitutive activation of SSc dermal fibroblasts by antagonizing the antifibrotic effect of TNF. Progranulin may also be involved in the inflammatory process associated with progressive skin sclerosis in early dcSSc. © 2015, American College of Rheumatology.

Impact of matrix stiffness on fibroblast function

Energy Technology Data Exchange (ETDEWEB)

El-Mohri, Hichem; Wu, Yang; Mohanty, Swetaparna; Ghosh, Gargi, E-mail: gargi@umich.edu

2017-05-01

Chronic non-healing wounds, caused by impaired production of growth factors and reduced vascularization, represent a significant burden to patients, health care professionals, and health care system. While several wound dressing biomaterials have been developed, the impact of the mechanical properties of the dressings on the residing cells and consequently on the healing of the wounds is largely overlooked. The primary focus of this study is to explore whether manipulation of the substrate mechanics can regulate the function of fibroblasts, particularly in the context of their angiogenic activity. A photocrosslinkable hydrogel platform with orthogonal control over gel modulus and cell adhesive sites was developed to explore the quantitative relationship between ECM compliance and fibroblast function. Increase in matrix stiffness resulted in enhanced fibroblast proliferation and stress fiber formation. However, the angiogenic activity of fibroblasts was found to be optimum when the cells were seeded on compliant matrices. Thus, the observations suggest that the stiffness of the wound dressing material may play an important role in the progression of wound healing. - Highlights: • Proliferation and stress fiber formation of fibroblasts increase with increasing matrix mechanics. • Cell area correlates with the growth of fibroblasts. • Angiogenic activity of fibroblasts optimum when cells seeded on compliant gels.

Clonogenic growth of human breast cancer cells co-cultured in direct contact with serum-activated fibroblasts

International Nuclear Information System (INIS)

Samoszuk, Michael; Tan, Jenny; Chorn, Guillaume

2005-01-01

Accumulating evidence suggests that fibroblasts play a pivotal role in promoting the growth of breast cancer cells. The objective of the present study was to characterize and validate an in vitro model of the interaction between small numbers of human breast cancer cells and human fibroblasts. We measured the clonogenic growth of small numbers of human breast cancer cells co-cultured in direct contact with serum-activated, normal human fibroblasts. Using DNA microarrays, we also characterized the gene expression profile of the serum-activated fibroblasts. In order to validate the in vivo relevance of our experiments, we then analyzed clinical samples of metastatic breast cancer for the presence of myofibroblasts expressing α-smooth muscle actin. Clonogenic growth of human breast cancer cells obtained directly from in situ and invasive tumors was dramatically and consistently enhanced when the tumor cells were co-cultured in direct contact with serum-activated fibroblasts. This effect was abolished when the cells were co-cultured in transwells separated by permeable inserts. The fibroblasts in our experimental model exhibited a gene expression signature characteristic of 'serum response' (i.e. myofibroblasts). Immunostaining of human samples of metastatic breast cancer tissue confirmed that myofibroblasts are in direct contact with breast cancer cells. Serum-activated fibroblasts promote the clonogenic growth of human breast cancer cells in vitro through a mechanism that involves direct physical contact between the cells. This model shares many important molecular and phenotypic similarities with the fibroblasts that are naturally found in breast cancers

Chemopreventive effects of a curcumin-like diarylpentanoid [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] in cellular targets of rheumatoid arthritis in vitro.

Science.gov (United States)

Lee, Ka-Heng; Abas, Faridah; Mohamed Alitheen, Noorjahan Banu; Shaari, Khozirah; Lajis, Nordin Haji; Israf, Daud Ahmad; Syahida, Ahmad

2015-07-01

Synovial fibroblast has emerged as a potential cellular target in progressive joint destruction in rheumatoid arthritis development. In this study, BDMC33 (2,6-bis[2,5-dimethoxybenzylidene]cyclohexanone), a curcumin analogue with enhanced anti-inflammatory activity has been synthesized and the potency of BDMC33 on molecular and cellular basis of synovial fibroblasts (SF) were evaluated in vitro. Synovial fibroblast cells (HIG-82) were cultured in vitro and induced by phorbol-12-myristate acetate (PMA) to stimulate the expression of matrix metalloproteinase (MMPs) and pro-inflammatory cytokines. The protective effects of BDMC33 were evaluated toward MMP activities, pro-inflammatory cytokine expression and nuclear factor kappa-B (NF-κB) activation by using various bioassay methods, including zymography, Western blotting, reverse transcription polymerase chain reaction, immunofluorescense microscopy and electrophoretic mobility shift assay. The results showed that BDMC33 significantly inhibited the pro-gelatinase B (pro-MMP-9) and collagenase activities via suppression of MMP-1 in activated SF. In addition, BDMC33 strongly suppressed MMP-3 gene expression as well as inhibited COX-2 and IL-6 pro-inflammatory gene expression. We also demonstrated that BDMC33 abolished the p65 NF-κB nuclear translocation and NF-κB DNA binding activity in PMA-stimulated SF. BDMC33 represents an effective chemopreventive agent and could be used as a promising lead compound for further development of rheumatoid arthritis therapeutic intervention. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Stromal cell markers are differentially expressed in the synovial tissue of patients with early arthritis

NARCIS (Netherlands)

Choi, Ivy Y.; Karpus, Olga N.; Turner, Jason D.; Hardie, Debbie; Marshall, Jennifer L.; de Hair, Maria J. H.; Maijer, Karen I.; Tak, Paul P.; Raza, Karim; Hamann, Jörg; Buckley, Christopher D.; Gerlag, Danielle M.; Filer, Andrew

2017-01-01

Previous studies have shown increased expression of stromal markers in synovial tissue (ST) of patients with established rheumatoid arthritis (RA). Here, ST expression of stromal markers in early arthritis in relationship to diagnosis and prognostic outcome was studied. ST from 56 patients included

Sex-Specific Protection of Osteoarthritis by Deleting Cartilage Acid Protein 1.

Science.gov (United States)

Ge, Xianpeng; Ritter, Susan Y; Tsang, Kelly; Shi, Ruirui; Takei, Kohtaro; Aliprantis, Antonios O

2016-01-01

Cartilage acidic protein 1 (CRTAC1) was recently identified as an elevated protein in the synovial fluid of patients with osteoarthritis (OA) by a proteomic analysis. This gene is also upregulated in both human and mouse OA by transcriptomic analysis. The objective of this study was to characterize the expression and function of CRTAC1 in OA. Here, we first confirm the increase of CRTAC1 in cartilage biopsies from OA patients undergoing joint replacement by real-time PCR and immunohistochemistry. Furthermore, we report that proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha upregulate CRTAC1 expression in primary human articular chondrocytes and synovial fibroblasts. Genetic deletion of Crtac1 in mice significantly inhibited cartilage degradation, osteophyte formation and gait abnormalities of post-traumatic OA in female, but not male, animals undergoing the destabilization of medial meniscus (DMM) surgery. Taken together, CRTAC1 is upregulated in the osteoarthritic joint and directly induced in chondrocytes and synovial fibroblasts by pro-inflammatory cytokines. This molecule is necessary for the progression of OA in female mice after DMM surgery and thus represents a potential therapy for this prevalent disease, especially for women who demonstrate higher rates and more severe OA.

Hairy polyelectrolyte brushes-grafted thermosensitive microgels as artificial synovial fluid for simultaneous biomimetic lubrication and arthritis treatment.

Science.gov (United States)

Liu, Guoqiang; Liu, Zhilu; Li, Na; Wang, Xiaolong; Zhou, Feng; Liu, Weimin

2014-11-26

We report the fabrication of poly(3-sulfopropyl methacrylate potassium salt) (PSPMK) brushes grafted poly(N-isopropylacrylamide) (PNIPAAm) microgels and their potential as artificial synovial fluid for biomimetic aqueous lubrication and arthritis treatment. The negatively charged PSPMK brushes and thermosensitive PNIPAAm microgels play water-based hydration lubrication and temperature-triggered drug release, respectively. Under soft friction pairs, an ultralow coefficient of friction was achieved, while the hairy thermosensitive microgels showed a desirable temperature-triggered drugs release performance. Such a soft charged hairy microgel offers great possibility for designing intelligent synovial fluid. What is more, the combination of lubrication and drug loading capabilities enables the large clinical potential of novel soft hairy nanoparticles as synthetic joint lubricant fluid in arthritis treatment.

Synovial cysts of the lumbar spine; diagnosed with magnetic resonance

International Nuclear Information System (INIS)

Bermudez Munoz, Sonia; Charry Lopez, Marco Luciano

1998-01-01

A series of nine cases of synovial cysts of the lumbar spine, diagnosed with magnetic resonance is presented. The cysts were found in patients aged 24 to 73 yrs, most of which had symptoms related with this finding. Some were seen as incidental findings or unrelated to symptoms. The most typical characteristic of these lesions is that of a rounded, ovoid or bilobed image, with close anatomical relation with the facet joints or the ligamentum flavum, that presented with facet joint arthrosis and degenerative spondylolisthesis was significant and useful for diagnosis

Subcutaneous phaeohyphomycosis due to Pyrenochaeta romeroi mimicking a synovial cyst

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Aurelien Dinh

2016-08-01

Full Text Available Opportunistic subcutaneous fungal infections are increasing nowadays due to the growing number of medical conditions causing immunosuppression, especially organ transplant. The incidence rate of subcutaneous phaeohyphomycosis is very low. Most studies found are case reports. They showed a wide variation of clinical presentations. Pyrenochaeta romeroi, a fungus from the Dematiaceae group is a saprophyte found in soil and plants and a possible causative agent of phaeohyphomycosis. We present a rare case of subcutaneous phaeohyphomycosis caused by P. romeroi mimicking a synovial cyst in a diabetic patient.

Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing.

Science.gov (United States)

Janda, Jaroslav; Nfonsam, Valentine; Calienes, Fernanda; Sligh, James E; Jandova, Jana

2016-05-01

Mitochondria are the major source of reactive oxygen species (ROS) in fibroblasts which are thought to be crucial regulators of wound healing with a potential to affect the expression of nuclear genes involved in this process. ROS generated by mitochondria are involved in all stages of tissue repair process but the regulation of ROS-generating system in fibroblasts still remains poorly understood. The purpose of this study was to better understand molecular mechanisms of how the regulation of ROS levels generated by mitochondria may influence the process of wound repair. Cybrid model system of mtDNA variations was used to study the functional consequences of altered ROS levels on wound healing responses in a uniform nuclear background of cultured ρ(0) fibroblasts. Mitochondrial ROS in cybrids were modulated by antioxidants that quench ROS to examine their ability to close the wound. Real-time PCR arrays were used to investigate whether ROS generated by specific mtDNA variants have the ability to alter expression of some key nuclear-encoded genes central to the wound healing response and oxidative stress. Our data suggest levels of mitochondrial ROS affect expression of some nuclear encoded genes central to wound healing response and oxidative stress and modulation of mitochondrial ROS by antioxidants positively affects in vitro process of wound closure. Thus, regulation of mitochondrial ROS-generating system in fibroblasts can be used as effective natural redox-based strategy to help treat non-healing wounds.

Different approaches to synovial membrane volume determination by magnetic resonance imaging: manual versus automated segmentation

DEFF Research Database (Denmark)

Østergaard, Mikkel

1997-01-01

Automated fast (5-20 min) synovial membrane volume determination by MRI, based on pre-set post-gadolinium-DTPA enhancement thresholds, was evaluated as a substitute for a time-consuming (45-120 min), previously validated, manual segmentation method. Twenty-nine knees [rheumatoid arthritis (RA) 13...

Structure of rat acidic fibroblast growth factor at 1.4 Å resolution

International Nuclear Information System (INIS)

Kulahin, Nikolaj; Kiselyov, Vladislav; Kochoyan, Arthur; Kristensen, Ole; Kastrup, Jette Sandholm; Berezin, Vladimir; Bock, Elisabeth; Gajhede, Michael

2007-01-01

The structure of rat acidic fibroblast growth factor was determined and compared with those of human, bovine and newt origin. The rat and human structures were found to be very similar. Fibroblast growth factors (FGFs) constitute a family of 22 structurally related heparin-binding polypeptides that are involved in the regulation of cell growth, survival, differentiation and migration. Here, a 1.4 Å resolution X-ray structure of rat FGF1 is presented. Two molecules are present in the asymmetric unit of the crystal and they coordinate a total of five sulfate ions. The structures of human, bovine and newt FGF1 have been published previously. Human and rat FGF1 are found to have very similar structures

Rac inhibition reverses the phenotype of fibrotic fibroblasts.

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Shi-wen Xu

Full Text Available BACKGROUND: Fibrosis, the excessive deposition of scar tissue by fibroblasts, is one of the largest groups of diseases for which there is no therapy. Fibroblasts from lesional areas of scleroderma patients possess elevated abilities to contract matrix and produce alpha-smooth muscle actin (alpha-SMA, type I collagen and CCN2 (connective tissue growth factor, CTGF. The basis for this phenomenon is poorly understood, and is a necessary prerequisite for developing novel, rational anti-fibrotic strategies. METHODS AND FINDINGS: Compared to healthy skin fibroblasts, dermal fibroblasts cultured from lesional areas of scleroderma (SSc patients possess elevated Rac activity. NSC23766, a Rac inhibitor, suppressed the persistent fibrotic phenotype of lesional SSc fibroblasts. NSC23766 caused a decrease in migration on and contraction of matrix, and alpha-SMA, type I collagen and CCN2 mRNA and protein expression. SSc fibroblasts possessed elevated Akt phosphorylation, which was also blocked by NSC23766. Overexpression of rac1 in normal fibroblasts induced matrix contraction and alpha-SMA, type I collagen and CCN2 mRNA and protein expression. Rac1 activity was blocked by PI3kinase/Akt inhibition. Basal fibroblast activity was not affected by NSC23766. CONCLUSION: Rac inhibition may be considered as a novel treatment for the fibrosis observed in SSc.

Changes of synovial fluid protein concentrations in supra-patellar bursitis patients after the injection of different molecular weights of hyaluronic acid.

Science.gov (United States)

Chen, Carl P C; Hsu, Chih Chin; Pei, Yu-Cheng; Chen, Ruo Li; Zhou, Shaobo; Shen, Hsuan-Chen; Lin, Shih-Cherng; Tsai, Wen Chung

2014-04-01

Knee pain is commonly seen in orthopedic and rehabilitation outpatient clinical settings, and in the aging population. Bursitis of the knee joint, especially when the volume of the synovial fluid is large enough, can compress and distend the nearby soft tissues, causing pain in the knee joint. Out of all the bursae surrounding the knee joint, supra-patellar bursitis is most often associated with knee pain. Treatment strategies in managing supra-patellar bursitis include the aspiration of joint synovial fluid and then followed by steroid injection into the bursa. When supra-patellar bursitis is caused by degenerative disorders, the concept of viscosupplementation treatment may be effective by injecting hyaluronic acid into the bursa. However, the rheology or the changes in the concentrations of proteins (biomarkers) that are related to the development of bursitis in the synovial fluid is virtually unexplored. Therefore, this study aimed to identify the concentration changes in the synovial fluid total protein amount and individual proteins associated with supra-patellar bursitis using the Bradford protein assay and western immunoglobulin methods. A total of 20 patients were divided into two groups with 10 patients in each group. One group received the high molecular weight hyaluronic acid product of Synvisc Hylan G-F 20 and the other group received the low molecular weight hyaluronic acid product of Hya-Joint Synovial Fluid Supplement once per week injection into the bursa for a total of 3 weeks. Significant decreases in the synovial fluid total protein concentrations were observed after the second dosage of high molecular weight hyaluronic acid injections. Apolipoprotein A-I, interleukin 1 beta, alpha 1 antitrypsin, and matrix metalloproteinase 1 proteins revealed a trend of decreasing western immunoblotting band densities after hyaluronic acid injections. The decreases in apolipoprotein A-I and interleukin 1 beta protein band densities were significant in the high

Cancer associated fibroblasts (CAFs) are activated in cutaneous basal cell carcinoma and in the peritumoural skin

DEFF Research Database (Denmark)

Omland, Silje Haukali; Wettergren, Erika Elgstrand; Mollerup, Sarah

2017-01-01

of chemokines involved in tumour progression and immunosuppression (CXCL12, CCL17). Fibroblasts from chronically sun-exposed skin near tumours show gene expression patterns resembling that of CAFs, indicating that stromal fibroblasts in cancer-free surgical BCC margins exhibit a tumour promoting phenotype.......BACKGROUND: Cutaneous basal cell carcinoma (BCC) is the commonest cancer worldwide. BCC is locally invasive and the surrounding stromal microenvironment is pivotal for tumourigenesis. Cancer associated fibroblasts (CAFs) in the microenvironment are essential for tumour growth in a variety...... of neoplasms but their role in BCC is poorly understood. METHODS: Material included facial BCC and control skin from the peritumoural area and from the buttocks. With next-generation sequencing (NGS) we compared mRNA expression between BCC and peritumoural skin. qRT-PCR, immunohistochemical...

Cancer associated fibroblasts (CAFs) are activated in cutaneous basal cell carcinoma and in the peritumoural skin

DEFF Research Database (Denmark)

Omland, Silje Haukali; Wettergren, Erika Elgstrand; Mourier, Tobias

2017-01-01

of chemokines involved in tumour progression and immunosuppression (CXCL12, CCL17). Fibroblasts from chronically sun-exposed skin near tumours show gene expression patterns resembling that of CAFs, indicating that stromal fibroblasts in cancer-free surgical BCC margins exhibit a tumour promoting phenotype.......Background: Cutaneous basal cell carcinoma (BCC) is the commonest cancer worldwide. BCC is locally invasive and the surrounding stromal microenvironment is pivotal for tumourigenesis. Cancer associated fibroblasts (CAFs) in the microenvironment are essential for tumour growth in a variety...... of neoplasms but their role in BCC is poorly understood. Methods: Material included facial BCC and control skin from the peritumoural area and from the buttocks. With next-generation sequencing (NGS) we compared mRNA expression between BCC and peritumoural skin. qRT-PCR, immunohistochemical...

25-Hydroxycholesterol promotes fibroblast-mediated tissue remodeling through NF-κB dependent pathway

International Nuclear Information System (INIS)

Ichikawa, Tomohiro; Sugiura, Hisatoshi; Koarai, Akira; Kikuchi, Takashi; Hiramatsu, Masataka; Kawabata, Hiroki; Akamatsu, Keiichiro; Hirano, Tsunahiko; Nakanishi, Masanori; Matsunaga, Kazuto; Minakata, Yoshiaki; Ichinose, Masakazu

2013-01-01

Abnormal structural alterations termed remodeling, including fibrosis and alveolar wall destruction, are important features of the pathophysiology of chronic airway diseases such as chronic obstructive pulmonary disease (COPD) and asthma. 25-hydroxycholesterol (25-HC) is enzymatically produced by cholesterol 25-hydorxylase (CH25H) in macrophages and is reported to be involved in the formation of arteriosclerosis. We previously demonstrated that the expression of CH25H and production of 25HC were increased in the lungs of COPD. However, the role of 25-HC in lung tissue remodeling is unknown. In this study, we investigated the effect of 25-HC on fibroblast-mediated tissue remodeling using human fetal lung fibroblasts (HFL-1) in vitro. 25-HC significantly augmented α-smooth muscle actin (SMA) (P 1 production (P 1 release. These results suggest that 25-HC could contribute to fibroblast-mediated lung tissue remodeling by promoting myofibroblast differentiation and the excessive release of extracellular matrix protein and MMPs via an NF-κB-TGF-β dependent pathway

Lumbar spine joint synovial cysts of intraspinal development. CT scan imaging

Energy Technology Data Exchange (ETDEWEB)

Vallee, C.; Chevrot, A.; Benhamouda, M. and others

CT scan imaging findings are described in 22 patients with lumbar spine joint synovial cysts, of intraspinal development, provoking sciatica or lumbosciatica from nerve compression in spinal canal. Diagnosis was suggested by a mass at the posterior joint level, of variable density, sometimes with peripheral calcification, presenting a vacuum appearance on occasions, and with enhanced image with contrast. Differential diagnosis is from excluded hernia and postoperative fibrosis. Posterior intra-articular arthrography can confirm diagnosis and allow treatment with prolonged action corticoid infiltrations.

Agreement of manual cell counts and automated counts of the scil Vet abc Plus(+) hematology analyzer for analysis of equine synovial fluid.

Science.gov (United States)

Van de Water, Eline; Oosterlinck, Maarten; Duchateau, Luc; Pille, Frederik

2016-06-01

The purpose of this study was to determine whether the scil Vet abc Plus(+) (SCIL Animal Care Company, Altorf, France), an impedance hematology analyzer, can accurately quantify and differentiate nucleated blood cells (NBCs) in equine synovial fluid. Synovial fluid samples (n=242) in different stages of experimentally induced inflammation were analyzed with and without hyaluronidase pretreatment and compared to manual hemocytometer counts and smear reviews. No significant effect of hyaluronidase pretreatment was observed. Total nucleated cell counts of the scil Vet abc Plus(+) were significantly higher compared to the manual method (P=0.02), yet the difference was small and clinically irrelevant (ratio manual/automated count equal to 0.97 with 95% CI [0.95, 1.00]). Differential cell counts of the scil Vet abc Plus(+) were not accurate. In conclusion, the scil Vet abc Plus(+) hematology analyzer is highly accurate for quantification, but not accurate for differentiation of NBCs in equine synovial fluid. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bacterial lipopolysaccharide promotes profibrotic activation of intestinal fibroblasts.

LENUS (Irish Health Repository)

Burke, J P

2012-02-01

BACKGROUND: Fibroblasts play a critical role in intestinal wound healing. Lipopolysaccharide (LPS) is a cell wall component of commensal gut bacteria. The effects of LPS on intestinal fibroblast activation were characterized. METHODS: Expression of the LPS receptor, toll-like receptor (TLR) 4, was assessed in cultured primary human intestinal fibroblasts using flow cytometry and confocal microscopy. Fibroblasts were treated with LPS and\\/or transforming growth factor (TGF) beta1. Nuclear factor kappaB (NFkappaB) pathway activation was assessed by inhibitory kappaBalpha (IkappaBalpha) degradation and NFkappaB promoter activity. Fibroblast contractility was measured using a fibroblast-populated collagen lattice. Smad-7, a negative regulator of TGF-beta1 signalling, and connective tissue growth factor (CTGF) expression were assessed using reverse transcriptase-polymerase chain reaction and western blot. The NFkappaB pathway was inhibited by IkappaBalpha transfection. RESULTS: TLR-4 was present on the surface of intestinal fibroblasts. LPS treatment of fibroblasts induced IkappaBalpha degradation, enhanced NFkappaB promoter activity and increased collagen contraction. Pretreatment with LPS (before TGF-beta1) significantly increased CTGF production relative to treatment with TGF-beta1 alone. LPS reduced whereas TGF-beta1 increased smad-7 expression. Transfection with an IkappaBalpha plasmid enhanced basal smad-7 expression. CONCLUSION: Intestinal fibroblasts express TLR-4 and respond to LPS by activating NFkappaB and inducing collagen contraction. LPS acts in concert with TGF-beta1 to induce CTGF. LPS reduces the expression of the TGF-beta1 inhibitor, smad-7.

[Imaging of the elbow joint with focus MRI. Part 2: muscles, nerves and synovial membranes].

Science.gov (United States)

Rehm, J; Zeifang, F; Weber, M-A

2014-03-01

This review article discusses the magnetic resonance imaging (MRI) features and pathological changes of muscles, nerves and the synovial lining of the elbow joint. Typical imaging findings are illustrated and discussed. In addition, the cross-sectional anatomy and anatomical variants, such as accessory muscles and plicae are discussed. Injuries of the muscles surrounding the elbow joint, as well as chronic irritation are particularly common in athletes. Morphological changes in MRI, for example tennis or golfer's elbow are typical and often groundbreaking. By adapting the examination sequences, imaging planes and slices, complete and incomplete tendon ruptures can be reliably diagnosed. Although the clinical and electrophysiological examinations form the basis for the diagnosis of peripheral neuropathies, MRI provides useful additional information about the precise localization due to its high resolution and good soft tissue contrast and helps to rule out differential diagnoses. Synovial diseases, such as inflammatory arthritis, proliferative diseases and also impinging plicae must be considered in the MRI diagnostics of the elbow joint.

Microscopical analysis of synovial fluid wear debris from failing CoCr hip prostheses

Science.gov (United States)

Ward, M. B.; Brown, A. P.; Cox, A.; Curry, A.; Denton, J.

2010-07-01

Metal on metal hip joint prostheses are now commonly implanted in patients with hip problems. Although hip replacements largely go ahead problem free, some complications can arise such as infection immediately after surgery and aseptic necrosis caused by vascular complications due to surgery. A recent observation that has been made at Manchester is that some Cobalt Chromium (CoCr) implants are causing chronic pain, with the source being as yet unidentified. This form of replacement failure is independent of surgeon or hospital and so some underlying body/implant interface process is thought to be the problem. When the synovial fluid from a failed joint is examined particles of metal (wear debris) can be found. Transmission Electron Microscopy (TEM) has been used to look at fixed and sectioned samples of the synovial fluid and this has identified fine (< 100 nm) metal and metal oxide particles within the fluid. TEM EDX and Electron Energy Loss Spectroscopy (EELS) have been employed to examine the composition of the particles, showing them to be chromium rich. This gives rise to concern that the failure mechanism may be associated with the debris.

Keratinocyte growth factor mRNA expression in periodontal ligament fibroblasts

DEFF Research Database (Denmark)

Dabelsteen, S; Wandall, H H; Grøn, B

1997-01-01

Keratinocyte growth factor (KGF) is a fibroblast growth factor which mediates epithelial growth and differentiation. KGF is expressed in subepithelial fibroblasts, but generally not in fibroblasts of deep connective tissue, such as fascia and ligaments. Here we demonstrate that KGF mRNA is expres......Keratinocyte growth factor (KGF) is a fibroblast growth factor which mediates epithelial growth and differentiation. KGF is expressed in subepithelial fibroblasts, but generally not in fibroblasts of deep connective tissue, such as fascia and ligaments. Here we demonstrate that KGF m......RNA is expressed in periodontal ligament fibroblasts, and that the expression is increased upon serum stimulation. Fibroblasts from human periodontal ligament, from buccal mucosa, from gingiva, and from skin were established from explants. Alkaline phosphatase activity was used as an indicator of the periodontal...

Posterior mediastinal biphasic synovial sarcoma in a 12 year-old boy: A case report and review of literature

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Pal Madhumay

2010-01-01

Full Text Available We report a case of biphasic synovial sarcoma of the mediastinum, a very rare tumor, in a 12-year-old boy with left-sided chest pain of 3 years duration at presentation. Chest X-ray showed left-sided opacity with loss of cardiac silhouette and the mediastinum deviated to the opposite side. Computed tomography (CT of thorax showed left-sided posterior mediastinal mass with left-sided pleural effusion and pleural thickening. CT guided fine needle aspiration cytology (FNAC from the mass reported it as spindle cell variant of adenocarcinoma. Ultrasonography (USG of the whole abdomen revealed no abnormality. The mediastinal tumor was resected by left thoracotomy and histopathological report confirmed it to be a biphasic synovial sarcoma with capsule invasion at places.

Cartilage proteoglycans inhibit fibronectin-mediated adhesion

Science.gov (United States)

Rich, A. M.; Pearlstein, E.; Weissmann, G.; Hoffstein, S. T.

1981-09-01

Normal tissues and organs show, on histological examination, a pattern of cellular and acellular zones that is characteristic and unique for each organ or tissue. This pattern is maintained in health but is sometimes destroyed by disease. For example, in mobile joints, the articular surfaces consist of relatively acellular hyaline cartilage, and the joint space is enclosed by a capsule of loose connective tissue with a lining of fibroblasts and macrophages. In the normal joint these cells are confined to the synovial lining and the articular surface remains acellular. In in vitro culture, macrophages and their precursor monocytes are very adhesive, and fibroblasts can migrate and overgrow surfaces such as collagen or plastic used for tissue culture. The fibroblasts adhere to collagen by means of fibronectin, which they synthesize and secrete1. Because the collagen of cartilage is capable of binding serum fibronectin2 and fibronectin is present in cartilage during its development3, these cells should, in theory, slowly migrate from the synovial lining to the articular surface. It is their absence from the articular cartilage in normal circumstances, and then presence in such pathological states as rheumatoid arthritis, that is striking. We therefore set out to determine whether a component of cartilage could prevent fibroblast adherence in a defined adhesion assay. As normal cartilage is composed of 50% proteoglycans and 50% collagen by dry weight4, we tested the possibility that the proteoglycans in cartilage inhibit fibroblast adhesion to collagen. We present here evidence that fibroblast spreading and adhesion to collagenous substrates is inhibited by cartilage proteoglycans.

Synovial tissue heterogeneity in rheumatoid arthritis in relation to disease activity and biomarkers in peripheral blood

NARCIS (Netherlands)

van Baarsen, Lisa G. M.; Wijbrandts, Carla A.; Timmer, Trieneke C. G.; van der Pouw Kraan, Tineke C. T. M.; Tak, Paul P.; Verweij, Cornelis L.

2010-01-01

OBJECTIVE: To investigate the clinical relevance of synovial tissue subtypes in rheumatoid arthritis (RA) and to search for peripheral blood (PB) markers that may serve as biomarkers for tissue subtypes. METHODS: Gene expression analysis using complementary DNA microarrays was applied on paired

The dual regulation of substance P-mediated inflammation via human synovial mast cells in rheumatoid arthritis

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Yuki Okamura

2017-09-01

Conclusions: Activated synovial MCs may rapidly degrade SP, which may downregulate the SP-mediated activation of synoviocytes in RA. On the other hand, SP activates MCs to induce inflammatory mediators, suggesting the dual regulation of SP-mediated inflammation by MCs in RA.

MR tomography of hemophilic osteoarthropathy with special reference to synovial and chondrogenic alterations. MR-Tomographie der haemophilen Osteoarthropathie unter besonderer Beruecksichtigung der synovialen und chondrogenen Alterationen

Energy Technology Data Exchange (ETDEWEB)

Erlemann, R. (St. Johannes-Hospital, Inst. fuer Radiologie, Duisburg-Hamborn (Germany)); Pollmann, H. (Westfaelische Wilhelms-Univ. Muenster, Kinderklinik, Abt. Haematologie und Onkologie (Germany)); Vestring, T.; Peters, P.E. (Westfaelische Wilhelms-Univ. Muenster, Inst. fuer Klinische Radiologie (Germany))

1992-03-01

52 knee and ankle joints of hemophiliacs were examined by MRI using FLASH and FISP-3-D sequences; and the degree of synovial hypertrophy and of cartilage destruction were assessed. Findings of synovial hypertrophy varied between thin membranes and tumorous tissue destroying the joint cartilage. Degree of cartilage destruction varied between focal signal decrease and total loss. In spite of recurrent joint bleedings no synovial or cartilaginous changes were seen in 31% and 29% of joints, respectively. Changes were more frequently seen and degree was more marked in the ankle than in the knee joints. With the exception of cysts, osseous destruction was more obvious with radiographs. MRI is suitable for the investigation of joints of hemophiliacs showing no osseous destruction. (orig.).

Helium generated cold plasma finely regulates activation of human fibroblast-like primary cells.

Directory of Open Access Journals (Sweden)

Paola Brun

Full Text Available Non-thermal atmospheric pressure plasmas are being developed for a wide range of health care applications, including wound healing. However in order to exploit the potential of plasma for clinical applications, the understanding of the mechanisms involved in plasma-induced activation of fibroblasts, the cells active in the healing process, is mandatory. In this study, the role of helium generated plasma in the tissue repairing process was investigated in cultured human fibroblast-like primary cells, and specifically in hepatic stellate cells and intestinal subepithelial myofibroblasts. Five minutes after treatment, plasma induced formation of reactive oxygen species (ROS in cultured cells, as assessed by flow cytometric analysis of fluorescence-activated 2',7'-dichlorofluorescein diacetate probe. Plasma-induced intracellular ROS were characterized by lower concentrations and shorter half-lives with respect to hydrogen peroxide-induced ROS. Moreover ROS generated by plasma treatment increased the expression of peroxisome proliferator activated receptor (PPAR-γ, nuclear receptor that modulates the inflammatory responses. Plasma exposure promoted wound healing in an in vitro model and induced fibroblast migration and proliferation, as demonstrated, respectively, by trans-well assay and partitioning between daughter cells of carboxyfluorescein diacetate succinimidyl ester fluorescent dye. Plasma-induced fibroblast migration and proliferation were found to be ROS-dependent as cellular incubation with antioxidant agents (e.g. N-acetyl L-cysteine cancelled the biological effects. This study provides evidence that helium generated plasma promotes proliferation and migration in liver and intestinal fibroblast-like primary cells mainly by increasing intracellular ROS levels. Since plasma-evoked ROS are time-restricted and elicit the PPAR-γ anti-inflammatory molecular pathway, this strategy ensures precise regulation of human fibroblast activation and

Infiltration of the synovial membrane with macrophage subsets and polymorphonuclear cells reflects global disease activity in spondyloarthropathy

NARCIS (Netherlands)

Baeten, Dominique; Kruithof, Elli; de Rycke, Leen; Boots, Anemieke M.; Mielants, Herman; Veys, Eric M.; de Keyser, Filip

2005-01-01

Considering the relation between synovial inflammation and global disease activity in rheumatoid arthritis (RA) and the distinct but heterogeneous histology of spondyloarthropathy (SpA) synovitis, the present study analyzed whether histopathological features of synovium reflect specific phenotypes

Sialylation regulates myofibroblast differentiation of human skin fibroblasts.

Science.gov (United States)

Sasaki, Norihiko; Itakura, Yoko; Toyoda, Masashi

2017-04-18

Fibroblasts are key players in maintaining skin homeostasis and in orchestrating physiological tissue repair and skin regeneration. Dysfunctions in fibroblasts that occur with aging and the senescent process lead to the delayed healing observed in elderly people. The molecular mechanisms leading to fibroblast dysfunction during aging and the senescent process have not yet been clarified. Previously, changes in patterns of glycosylation were observed in fibroblasts in aging and the senescent process, but the effect of these changes on the function of fibroblasts has not been well documented. Here, we investigated whether changes in glycosylation during the process to senescence may have functional effects on fibroblasts. The changes in cell surface glycans on skin fibroblasts during the process to senescence were examined in early-passage (EP) and late-passage (LP) skin fibroblasts by fluorescence-activated cell sorting analysis using lectins. The contributors to the changes in cell surface glycans were examined by real-time polymerase chain reaction or Western blot analysis. The effects of changes in glycosylation on proliferation, migration, induction of cellular senescence, and myofibroblast differentiation induced by transforming growth factor (TGF)-β1 stimulation were examined in EP fibroblasts. The changes in glycosylation were performed by GalNAc-α-O-benzyl or sialidase treatment. A decrease in sialylation of glycoproteins and an increase in sialidase NEU1 were observed in LP fibroblasts. The reduction of sialylation did not have any effect on proliferation, migration, or induction of cellular senescence. On the other hand, myofibroblast differentiation was inhibited by the reduction of sialylation, indicating that sialylation is important for myofibroblast differentiation. The localization of CD44 in lipid rafts, which is required for myofibroblast differentiation, was inhibited by the reduction of sialylation. Furthermore, reduced myofibroblast

Toll-like receptor 9 mediated responses in cardiac fibroblasts.

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Ingrid Kristine Ohm

Full Text Available Altered cardiac Toll-like receptor 9 (TLR9 signaling is important in several experimental cardiovascular disorders. These studies have predominantly focused on cardiac myocytes or the heart as a whole. Cardiac fibroblasts have recently been attributed increasing significance in mediating inflammatory signaling. However, putative TLR9-signaling through cardiac fibroblasts remains non-investigated. Thus, our aim was to explore TLR9-signaling in cardiac fibroblasts and investigate the consequence of such receptor activity on classical cardiac fibroblast cellular functions. Cultivated murine cardiac fibroblasts were stimulated with different TLR9 agonists (CpG A, B and C and assayed for the secretion of inflammatory cytokines (tumor necrosis factor α [TNFα], CXCL2 and interferon α/β. Expression of functional cardiac fibroblast TLR9 was proven as stimulation with CpG B and -C caused significant CXCL2 and TNFα-release. These responses were TLR9-specific as complete inhibition of receptor-stimulated responses was achieved by co-treatment with a TLR9-antagonist (ODN 2088 or chloroquine diphosphate. TLR9-stimulated responses were also found more potent in cardiac fibroblasts when compared with classical innate immune cells. Stimulation of cardiac fibroblasts TLR9 was also found to attenuate migration and proliferation, but did not influence myofibroblast differentiation in vitro. Finally, results from in vivo TLR9-stimulation with subsequent fractionation of specific cardiac cell-types (cardiac myocytes, CD45+ cells, CD31+ cells and cardiac fibroblast-enriched cell-fractions corroborated our in vitro data and provided evidence of differentiated cell-specific cardiac responses. Thus, we conclude that cardiac fibroblast may constitute a significant TLR9 responder cell within the myocardium and, further, that such receptor activity may impact important cardiac fibroblast cellular functions.

Matrix metalloproteinase inhibition reduces contraction by dupuytren fibroblasts.

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Townley, William A; Cambrey, Alison D; Khaw, Peng T; Grobbelaar, Adriaan O

2008-11-01

Dupuytren's disease is a common fibroproliferative condition of the hand characterized by fibrotic lesions (nodules and cords), leading to disability through progressive digital contracture. Although the etiology of the disease is poorly understood, recent evidence suggests that abnormal matrix metalloproteinase (MMP) activity may play a role in cell-mediated collagen contraction and tissue scarring. The aim of this study was to investigate the efficacy of ilomastat, a broad-spectrum MMP inhibitor, in an in vitro model of Dupuytren fibroblast-mediated contraction. Nodule-derived and cord-derived fibroblasts were isolated from Dupuytren patients; carpal ligament-derived fibroblasts acted as control. Stress-release fibroblast-populated collagen lattices (FPCLs) were used as a model of contraction. FPCLs were allowed to develop mechanical stress (48 hours) during treatment with ilomastat (0-100 micromol/L), released, and allowed to contract over a 48-hour period. Contraction was estimated by measuring lattice area compared with untreated cells or treatment with a control peptide. MMP-1, MMP-2, and MT1-MMP levels were assessed by zymography, Western blotting, and enzyme-linked immunosorbent assay. Nodule-derived fibroblasts contracted lattices (69% +/- 2) to a greater extent than did cord-derived (55% +/- 3) or carpal ligament-derived (55% +/- 1) fibroblasts. Exposure to ilomastat led to significant inhibition of lattice contraction by all fibroblasts, although a reduction in lattice contraction by nodule-derived fibroblasts was most prominent (84% +/- 8). In addition, treatment with ilomastat led to a concomitant suppression of MMP-1 and MMP-2 activity, whereas MT1-MMP activity was found to be upregulated. Our results demonstrate that inhibition of MMP activity results in a reduction in extracellular matrix contraction by Dupuytren fibroblasts and suggest that MMP activity may be a critical target in preventing recurrent contracture caused by this disease.

RhoA signaling modulates cyclin D1 expression in human lung fibroblasts; implications for idiopathic pulmonary fibrosis

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Hoban PR

2006-06-01

Full Text Available Abstract Background Idiopathic Pulmonary Fibrosis (IPF is a debilitating disease characterized by exaggerated extracellular matrix deposition and aggressive lung structural remodeling. Disease pathogenesis is driven by fibroblastic foci formation, consequent on growth factor overexpression and myofibroblast proliferation. We have previously shown that both CTGF overexpression and myofibroblast formation in IPF cell lines are dependent on RhoA signaling. As RhoA-mediated regulation is also involved in cell cycle progression, we hypothesise that this pathway is key to lung fibroblast turnover through modulation of cyclin D1 kinetic expression. Methods Cyclin D1 expression was compared in primary IPF patient-derived fibroblasts and equivalent normal control cells. Quantitative real time PCR was employed to examine relative expression levels of cyclin D1 mRNA; protein expression was confirmed by western blotting. Effects of Rho signaling were investigated using transient transfection of constitutively active and dominant negative RhoA constructs as well as pharmacological inhibitors. Cellular proliferation of lung fibroblasts was determined by BrdU incorporation ELISA. To further explore RhoA regulation of cyclin D1 in lung fibroblasts and associated cell cycle progression, an established Rho inhibitor, Simvastatin, was incorporated in our studies. Results Cyclin D1 expression was upregulated in IPF compared to normal lung fibroblasts under exponential growth conditions (p Conclusion These findings report for the first time that cyclin D1 expression is deregulated in IPF through a RhoA dependent mechanism that influences lung fibroblast proliferation. This potentially unravels new molecular targets for future anti-IPF strategies; accordingly, Simvastatin inhibition of Rho-mediated cyclin D1 expression in IPF fibroblasts merits further exploitation.

Mechanisms involved in the therapeutic effects of Paeonia lactiflora Pallas in rheumatoid arthritis.

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Zhang, Wei; Dai, Sheng-Ming

2012-09-01

Paeonia lactiflora Pallas, also named Chinese Paeony, is a Chinese herb. A decoction of its root has been used to treat painful or inflammatory disorders in traditional Chinese medicine. A water/ethanol extract of Radix Paeoniae is known as total glycosides of paeony (TGP), of which paeoniflorin is the major active component. Preclinical studies show that TGP/paeoniflorin is able to diminish pain, joint swelling, synovial hypertrophy, and the severity of bone erosion and cartilage degradation in experimental arthritis. TGP/paeoniflorin suppresses inflammatory process by reducing the production of prostaglandin E2, leukotriene B4, nitric oxide, reactive oxygen species, proinflammatory cytokines and chemokines. TGP/paeoniflorin also inhibits the proliferation of lymphocytes and fibroblast-like synoviocytes, the formation of new blood vessels, and the production of matrix metalloproteinases. Clinical data show that TGP is effective to relieve the symptoms and signs of rheumatoid arthritis without significant adverse effects. Recently, TGP is widely used to treat rheumatoid arthritis in China. Copyright © 2012 Elsevier B.V. All rights reserved.

Protective influence of hyaluronic acid on focal adhesion kinase activity in human skin fibroblasts exposed to ethanol.

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Donejko, Magdalena; Rysiak, Edyta; Galicka, Elżbieta; Terlikowski, Robert; Głażewska, Edyta Katarzyna; Przylipiak, Andrzej

2017-01-01

The aim of this study was to evaluate the effect of ethanol and hyaluronic acid (HA) on cell survival and apoptosis in cultured human skin fibroblasts. Regarding the mechanism of ethanol action on human skin fibroblasts, we investigated cell viability and apoptosis, expression of focal adhesion kinase (FAK), and the influence of HA on those processes. Studies were conducted in confluent human skin fibroblast cultures that were treated with 25 mM, 50 mM, and 100 mM ethanol or with ethanol and 500 µg/mL HA. Cell viability was examined using methyl thiazolyl tetrazolium (MTT) assay and NC-300 Nucleo-Counter. Imaging of the cells using a fluorescence microscope Pathway 855 was performed to measure FAK expression. Depending on the dosage, ethanol decreased cell viability and activated the process of apoptosis in human skin fibroblasts. HA prevented the negative influence of ethanol on cell viability and prevented apoptosis. The analysis of fluorescence imaging using BD Pathway 855 High-Content Bioimager showed the inhibition of FAK migration to the cell nucleus, depending on the increasing concentration of ethanol. This study proves that downregulation of signaling pathway of FAK is involved in ethanol-induced apoptosis in human skin fibroblasts. The work also indicates a protective influence of HA on FAK activity in human skin fibroblasts exposed to ethanol.

p53/PUMA expression in human pulmonary fibroblasts mediates cell activation and migration in silicosis.

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Wang, Wei; Liu, Haijun; Dai, Xiaoniu; Fang, Shencun; Wang, Xingang; Zhang, Yingming; Yao, Honghong; Zhang, Xilong; Chao, Jie

2015-11-18

Phagocytosis of SiO2 into the lung causes an inflammatory cascade that results in fibroblast proliferation and migration, followed by fibrosis. Clinical evidence has indicated that the activation of alveolar macrophages by SiO2 produces rapid and sustained inflammation characterized by the generation of monocyte chemotactic protein 1, which, in turn, induces fibrosis. However, the details of events downstream of monocyte chemotactic protein 1 activity in pulmonary fibroblasts remain unclear. Here, to elucidate the role of p53 in fibrosis induced by silica, both the upstream molecular mechanisms and the functional effects on cell proliferation and migration were investigated. Experiments using primary cultured adult human pulmonary fibroblasts led to the following results: 1) SiO2 treatment resulted in a rapid and sustained increase in p53 and PUMA protein levels; 2) the MAPK and PI3K pathways were involved in the SiO2-induced alteration of p53 and PUMA expression; and 3) RNA interference targeting p53 and PUMA prevented the SiO2-induced increases in fibroblast activation and migration. Our study elucidated a link between SiO2-induced p53/PUMA expression in fibroblasts and cell migration, thereby providing novel insight into the potential use of p53/PUMA in the development of novel therapeutic strategies for silicosis treatment.

A co-culture system with three different primary human cell populations reveals that biomaterials and MSC modulate macrophage-driven fibroblast recruitment.

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Caires, Hugo R; Barros da Silva, Patrícia; Barbosa, Mário A; Almeida, Catarina R

2018-03-01

The biological response to implanted biomaterials is a complex and highly coordinated phenomenon involving many different cell types that interact within 3D microenvironments. Here, we increased the complexity of a 3D platform to include at least 3 cell types that play a role in the host response upon scaffold implantation. With this system, it was possible to address how immune responses triggered by 3D biomaterials mediate recruitment of stromal cells that promote tissue regeneration, mesenchymal stromal/stem cells (MSC), or a foreign body response, fibroblasts. Primary human macrophages yielded the highest fibroblast recruitment when interacting with chitosan scaffolds but not polylactic acid. Interestingly, when there were MSC and fibroblasts in the same environment, macrophages in chitosan scaffolds again promoted a significant increase on fibroblast recruitment, but not of MSC. However, macrophages that were firstly allowed to interact with MSC within the scaffolds were no longer able to recruit fibroblasts. This study illustrates the potential to use different scaffolds to regulate the dynamics of recruitment of proregenerative or fibrotic cell types through immunomodulation. Overall, this work strengths the idea that ex vivo predictive systems need to consider the different players involved in the biological response to biomaterials and that timing of arrival of specific cell types will affect the outcome. Copyright © 2017 John Wiley & Sons, Ltd.

Interleukin-6 in serum and in synovial fluid enhances the differentiation between periprosthetic joint infection and aseptic loosening.

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Thomas M Randau

Full Text Available The preoperative differentiation between septic and aseptic loosening after total hip or knee arthroplasty is essential for successful therapy and relies in part on biomarkers. The objective of this study was to assess synovial and serum levels of inflammatory proteins as diagnostic tool for periprosthetic joint infection and compare their accuracy with standard tests. 120 patients presenting with a painful knee or hip endoprosthesis for surgical revision were included in this prospective trial. Blood samples and samples of intraoperatively acquired joint fluid aspirate were collected. White blood cell count, C-reactive protein, procalcitonin and interleukin-6 were determined. The joint aspirate was analyzed for total leukocyte count and IL-6. The definite diagnosis of PJI was determined on the basis of purulent synovial fluid, histopathology and microbiology. IL-6 in serum showed significantly higher values in the PJI group as compared to aseptic loosening and control, with specificity at 58.3% and a sensitivity of 79.5% at a cut-off value of 2.6 pg/ml. With a cut-off >6.6 pg/ml, the specificity increased to 88.3%. IL-6 in joint aspirate had, at a cut-off of >2100 pg/ml, a specificity of 85.7% and sensitivity of 59.4%. At levels >9000 pg/ml, specificity was almost at 100% with sensitivity just below 50%, so PJI could be considered proven with IL-6 levels above this threshold. Our data supports the published results on IL-6 as a biomarker in PJI. In our large prospective cohort of revision arthroplasty patients, the use of IL-6 in synovial fluid appears to be a more accurate marker than either the white blood cell count or the C-reactive protein level in serum for the detection of periprosthetic joint infection. On the basis of the results we recommend the use of the synovial fluid biomarker IL-6 for the diagnosis of periprosthetic joint infection following total hip and knee arthroplasty.

Interleukin-6 in serum and in synovial fluid enhances the differentiation between periprosthetic joint infection and aseptic loosening.

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Randau, Thomas M; Friedrich, Max J; Wimmer, Matthias D; Reichert, Ben; Kuberra, Dominik; Stoffel-Wagner, Birgit; Limmer, Andreas; Wirtz, Dieter C; Gravius, Sascha

2014-01-01

The preoperative differentiation between septic and aseptic loosening after total hip or knee arthroplasty is essential for successful therapy and relies in part on biomarkers. The objective of this study was to assess synovial and serum levels of inflammatory proteins as diagnostic tool for periprosthetic joint infection and compare their accuracy with standard tests. 120 patients presenting with a painful knee or hip endoprosthesis for surgical revision were included in this prospective trial. Blood samples and samples of intraoperatively acquired joint fluid aspirate were collected. White blood cell count, C-reactive protein, procalcitonin and interleukin-6 were determined. The joint aspirate was analyzed for total leukocyte count and IL-6. The definite diagnosis of PJI was determined on the basis of purulent synovial fluid, histopathology and microbiology. IL-6 in serum showed significantly higher values in the PJI group as compared to aseptic loosening and control, with specificity at 58.3% and a sensitivity of 79.5% at a cut-off value of 2.6 pg/ml. With a cut-off >6.6 pg/ml, the specificity increased to 88.3%. IL-6 in joint aspirate had, at a cut-off of >2100 pg/ml, a specificity of 85.7% and sensitivity of 59.4%. At levels >9000 pg/ml, specificity was almost at 100% with sensitivity just below 50%, so PJI could be considered proven with IL-6 levels above this threshold. Our data supports the published results on IL-6 as a biomarker in PJI. In our large prospective cohort of revision arthroplasty patients, the use of IL-6 in synovial fluid appears to be a more accurate marker than either the white blood cell count or the C-reactive protein level in serum for the detection of periprosthetic joint infection. On the basis of the results we recommend the use of the synovial fluid biomarker IL-6 for the diagnosis of periprosthetic joint infection following total hip and knee arthroplasty.

COMPARISON OF CULTURE OF SYNOVIAL FLUID, PERIPROSTHETIC TISSUE AND PROSTHESIS SONICATE FOR THE DIAGNOSIS OF KNEE PROSTHESIS INFECTION

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Andrej Trampuž

2003-03-01

Full Text Available Background. Synovial fluid and periprosthetic tissue specimens are the standard specimens cultured for the diagnosis of prosthetic joint infection (PJI. We hypothesize that ultrasonication of the explanted prosthesis may improve diagnosis of PJI by dislodging biofilm bacteria from the prosthesis surface and improve the sensitivity and specificity of diagnosis of PJI.Methods. Included were patients undergoing knee prosthesis exchange for septic or biomechanical failure and have not received antimicrobial therapy in the last 2 weeks prior specimen collection. Cultures of synovial fluid and periprosthetic tissue specimens were performed per the usual clinical practice. Additionally, explanted joint components were sonicated for 5 minutes at frequency 40 kHz in sterile Ringer’s solution; aliquots of 0.5 ml sonicate were plated onto five aerobic and five anaerobic blood agar plates, and incubated at 37 °C and examined for the next seven days. The number and identity of each colony morphology was recorded.Results. 35 patients undergoing knee replacement have been studied (24 for aseptic biomechanical failure and 11 for suspected PJI. In patients with PJI, coagulase-negative staphylococci (7 cases, Corynebacterium spp. (2 cases, Staphylococcus aureus (1 case, and viridans group streptococcus (1 case were recovered. Culture sensitivity and specificity were for synovial fluid 88% and 100%, for periprosthetic tissue 83% and 81%, and for explant sonicate 91% and 100%, respectively. In sonicate cultures higher numbers of microorganisms than in periprosthetic tissue cultures were consistently detected.Conclusions. Using synovial fluid, periprosthetic tissue, and explant sonicate cultures, 12%, 17% and 9% of PJI were missed, respectively. Explant sonicate cultures were the most sensitive with respect to the diagnosis of PJI, indicating that explant ultrasonication may improve bacterial recovery. In sonicate cultures, infecting organisms were detected in

Effects of polyhexamethylene guanidine phosphate on human gingival fibroblasts.

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Vitt, Anton; Slizen, Veronica; Boström, Elisabeth A; Yucel-Lindberg, Tülay; Kats, Anna; Sugars, Rachael V; Gustafsson, Anders; Buhlin, Kåre

2017-10-01

Polyhexamethylene guanidine phosphate (PHMG-P) was compared to chlorhexidine (CHX) in order to determine potential cytotoxic and immune-modulatory effects on human gingival fibroblasts. Cytotoxic effects of PHMG-P and CHX on human gingival fibroblasts were assessed using cell viability assay at various time points and concentrations. The effects of PHMG-P and CHX on the secretion of prostaglandin (PG) E 2 , interleukin (IL)-6, IL-8 and matrix metalloproteinase (MMP)-1 by non-stimulated or IL-1β stimulated fibroblasts were evaluated by enzyme-linked immunosorbent assays. PHMG-P concentration 0.00009% led to the total loss of fibroblast viability within 24 h, whereas inhibition of fibroblast viability by CHX occurred at significantly higher concentrations of 0.0009% (p PHMG-P led to loss of fibroblast viability after 5 min, whilst cells exposed to 0.005% CHX survived 30 min of treatment (p PHMG-P or CHX at concentrations of 0.000045 or 0.0.00009% resulted in significantly decreased PGE 2 , IL-6, IL-8 and MMP-1 levels. PHMG-P or CHX alone did not affect the baseline secretion of PGE 2 , IL-6, IL-8 or MMP-1 by gingival fibroblasts. Cytotoxic effects on gingival fibroblasts were triggered by both PHMG-P and CHX at concentrations below those used in clinical practice. The tested antiseptics did not cause inflammation and reduced IL-1β-induced secretion of inflammatory mediators and collagenase by gingival fibroblasts, which suggests anti-inflammatory properties.

Distinguishing multiple rice body formation in chronic subacromial-subdeltoid bursitis from synovial chondromatosis

International Nuclear Information System (INIS)

Chen, Albert; Wong, Lun-Yick; Sheu, Chin-Yin; Chen, Be-Fong

2002-01-01

Multiple rice body formation is a complication of chronic bursitis. Although it resembles synovial chondromatosis clinically and on imaging, the literature suggests that analysis of radiographic and MR appearances should allow discrimination. We report the imaging findings in a 41-year-old man presenting with rice body formation in chronic subacromial-subdeltoid bursitis. We found that the signal intensity of the rice bodies is helpful in making the diagnosis. (orig.)

Distinguishing multiple rice body formation in chronic subacromial-subdeltoid bursitis from synovial chondromatosis

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Chen, Albert; Wong, Lun-Yick; Sheu, Chin-Yin [Department of Radiology, Mackay Memorial Hospital, Taipei (Taiwan); Chen, Be-Fong [Department of Pathology, Mackay Memorial Hospital, Taipei (Taiwan)

2002-02-01

Multiple rice body formation is a complication of chronic bursitis. Although it resembles synovial chondromatosis clinically and on imaging, the literature suggests that analysis of radiographic and MR appearances should allow discrimination. We report the imaging findings in a 41-year-old man presenting with rice body formation in chronic subacromial-subdeltoid bursitis. We found that the signal intensity of the rice bodies is helpful in making the diagnosis. (orig.)

Mesenchymal stem cells induce dermal fibroblast responses to injury

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Smith, Andria N.; Willis, Elise; Chan, Vincent T.; Muffley, Lara A.; Isik, F. Frank; Gibran, Nicole S.; Hocking, Anne M.

2010-01-01

Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. When co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury.

LIF Mediates Proinvasive Activation of Stromal Fibroblasts in Cancer

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Jean Albrengues

2014-06-01

Full Text Available Signaling crosstalk between tumor cells and fibroblasts confers proinvasive properties to the tumor microenvironment. Here, we identify leukemia inhibitory factor (LIF as a tumor promoter that mediates proinvasive activation of stromal fibroblasts independent of alpha-smooth muscle actin (α-SMA expression. We demonstrate that a pulse of transforming growth factor β (TGF-β establishes stable proinvasive fibroblast activation by inducing LIF production in both fibroblasts and tumor cells. In fibroblasts, LIF mediates TGF-β-dependent actomyosin contractility and extracellular matrix remodeling, which results in collective carcinoma cell invasion in vitro and in vivo. Accordingly, carcinomas from multiple origins and melanomas display strong LIF upregulation, which correlates with dense collagen fiber organization, cancer cell collective invasion, and poor clinical outcome. Blockade of JAK activity by Ruxolitinib (JAK inhibitor counteracts fibroblast-dependent carcinoma cell invasion in vitro and in vivo. These findings establish LIF as a proinvasive fibroblast producer independent of α-SMA and may open novel therapeutic perspectives for patients with aggressive primary tumors.

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

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Østergaard, Mikkel; Hansen, M; Stoltenberg, M

1999-01-01

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 a......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......-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

Potensi Terapeutik Fibroblast Growth Factor 21 terhadap Resistensi Insulin

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Kurniasari Kurniasari

2015-12-01

Full Text Available Fibroblast growth factor 21 (FGF21 merupakan salah satu dari anggota FGF yang berperansebagai faktor endokrin. Hepar dan jaringan adiposa merupakan tempat kerja utama FGF21.Ekspresi FGF21 di hepar diatur oleh peroxisome proliferator activated receptor alpha (PPARαsedangkan di jaringan adiposa diatur oleh peroxisome proliferator activated receptor gamma(PPARγ. Kedua faktor transkripsi tersebut terlibat dalam metabolisme karbohidrat dan lipid. Padaresistensi insulin terdapat hiperglikemia, hiperinsulinemia, dan dislipidemia. Pemberian FGF21pada berbagai studi in vivo dan in vitro telah menunjukan potensi FGF21 dalam mengatasi kelainanakibat resistensi insulin sekaligus meningkatkan sensitivitas jaringan terhadap insulin. Kata kunci: FGF21, PPARγ, PPARα, resistensi insulin Fibroblast Growth Factor 21 (FGF21 Potension in InsulinResistance Treatment Abstract Fibroblast growth factor 21 (FGF21 is a member of FGF family that plays a role as endocrinefactor. Liver and adipose tissue are major target of FGF21. The expression of FGF21 in liveris regulated by peroxisome proliferator activated receptor alpha (PPARα, while peroxisomeproliferator activated receptor gamma (PPARγ regulate FGF21 expression in adipose tissue.Both transcription factors are involved in carbohydrate and lipid metabolism. Hyperglycemia,hyperinsulinemia, and dyslipidemia are observed in insulin resistance. Treatment with FGF21 inin vitro and in vivo study showed that FGF21 have the potential to overcome insulin resistance aswell as increasing tissue’s sensitivity towards insulin. Keywords: FGF21, PPARγ, PPARα, insulin resistance Normal 0 false false false IN X-NONE X-NONE

Sex-Specific Protection of Osteoarthritis by Deleting Cartilage Acid Protein 1.

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Xianpeng Ge

Full Text Available Cartilage acidic protein 1 (CRTAC1 was recently identified as an elevated protein in the synovial fluid of patients with osteoarthritis (OA by a proteomic analysis. This gene is also upregulated in both human and mouse OA by transcriptomic analysis. The objective of this study was to characterize the expression and function of CRTAC1 in OA. Here, we first confirm the increase of CRTAC1 in cartilage biopsies from OA patients undergoing joint replacement by real-time PCR and immunohistochemistry. Furthermore, we report that proinflammatory cytokines interleukin-1beta and tumor necrosis factor alpha upregulate CRTAC1 expression in primary human articular chondrocytes and synovial fibroblasts. Genetic deletion of Crtac1 in mice significantly inhibited cartilage degradation, osteophyte formation and gait abnormalities of post-traumatic OA in female, but not male, animals undergoing the destabilization of medial meniscus (DMM surgery. Taken together, CRTAC1 is upregulated in the osteoarthritic joint and directly induced in chondrocytes and synovial fibroblasts by pro-inflammatory cytokines. This molecule is necessary for the progression of OA in female mice after DMM surgery and thus represents a potential therapy for this prevalent disease, especially for women who demonstrate higher rates and more severe OA.

Effects of dynamic matrix remodelling on en masse migration of fibroblasts on collagen matrices.

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Ozcelikkale, Altug; Dutton, J Craig; Grinnell, Frederick; Han, Bumsoo

2017-10-01

Fibroblast migration plays a key role during various physiological and pathological processes. Although migration of individual fibroblasts has been well studied, migration in vivo often involves simultaneous locomotion of fibroblasts sited in close proximity, so-called ' en masse migration', during which intensive cell-cell interactions occur. This study aims to understand the effects of matrix mechanical environments on the cell-matrix and cell-cell interactions during en masse migration of fibroblasts on collagen matrices. Specifically, we hypothesized that a group of migrating cells can significantly deform the matrix, whose mechanical microenvironment dramatically changes compared with the undeformed state, and the alteration of the matrix microenvironment reciprocally affects cell migration. This hypothesis was tested by time-resolved measurements of cell and extracellular matrix movement during en masse migration on collagen hydrogels with varying concentrations. The results illustrated that a group of cells generates significant spatio-temporal deformation of the matrix before and during the migration. Cells on soft collagen hydrogels migrate along tortuous paths, but, as the matrix stiffness increases, cell migration patterns become aligned with each other and show coordinated migration paths. As cells migrate, the matrix is locally compressed, resulting in a locally stiffened and dense matrix across the collagen concentration range studied. © 2017 The Author(s).

LXA4 actions direct fibroblast function and wound closure

International Nuclear Information System (INIS)

Herrera, Bruno S.; Kantarci, Alpdogan; Zarrough, Ahmed; Hasturk, Hatice; Leung, Kai P.; Van Dyke, Thomas E.

2015-01-01

Timely resolution of inflammation is crucial for normal wound healing. Resolution of inflammation is an active biological process regulated by specialized lipid mediators including the lipoxins and resolvins. Failure of resolution activity has a major negative impact on wound healing in chronic inflammatory diseases that is manifest as excess fibrosis and scarring. Lipoxins, including Lipoxin A 4 (LXA 4 ), have known anti-fibrotic and anti-scarring properties. The goal of this study was to elucidate the impact of LXA 4 on fibroblast function. Mouse fibroblasts (3T3 Mus musculus Swiss) were cultured for 72 h in the presence of TGF-β1, to induce fibroblast activation. The impact of exogenous TGF-β1 (1 ng/mL) on LXA 4 receptor expression (ALX/FPR2) was determined by flow cytometry. Fibroblast proliferation was measured by bromodeoxyuridine (BrdU) labeling and migration in a “scratch” assay wound model. Expression of α-smooth muscle actin (α-SMA), and collagen types I and III were measured by Western blot. We observed that TGF-β1 up-regulates LXA 4 receptor expression, enhances fibroblast proliferation, migration and scratch wound closure. α-SMA levels and Collagen type I and III deposition were also enhanced. LXA 4 slowed fibroblast migration and scratch wound closure at early time points (24 h), but wound closure was equal to TGF-β1 alone at 48 and 72 h. LXA 4 tended to slow fibroblast proliferation at both concentrations, but had no impact on α-SMA or collagen production by TGF-β1 stimulated fibroblasts. The generalizability of the actions of resolution molecules was examined in experiments repeated with resolvin D2 (RvD2) as the agonist. The activity of RvD2 mimicked the actions of LXA 4 in all assays, through an as yet unidentified receptor. The results suggest that mediators of resolution of inflammation enhance wound healing and limit fibrosis in part by modulating fibroblast function. - Highlights: • TGF-β1 up-regulates LXA 4 receptor (ALX

Phase I vaccination trial of SYT-SSX junction peptide in patients with disseminated synovial sarcoma

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Asanuma Hiroko

2005-01-01

Full Text Available Abstract Background Synovial sarcoma is a high-grade malignant tumor of soft tissue, characterized by the specific chromosomal translocation t(X;18, and its resultant SYT-SSX fusion gene. Despite intensive multimodality therapy, the majority of metastatic or relapsed diseases still remain incurable, thus suggesting a need for new therapeutic options. We previously demonstrated the antigenicity of SYT-SSX gene-derived peptides by in vitro analyses. The present study was designed to evaluate in vivo immunological property of a SYT-SSX junction peptide in selected patients with synovial sarcoma. Methods A 9-mer peptide (SYT-SSX B: GYDQIMPKK spanning the SYT-SSX fusion region was synthesized. Eligible patients were those (i who have histologically and genetically confirmed, unresectable synovial sarcoma (SYT-SSX1 or SYT-SSX2 positive, (ii HLA-A*2402 positive, (iii between 20 and 70 years old, (iv ECOG performance status between 0 and 3, and (v who gave informed consent. Vaccinations with SYT-SSX B peptide (0.1 mg or 1.0 mg were given subcutaneously six times at 14-day intervals. These patients were evaluated for DTH skin test, adverse events, tumor size, tetramer staining, and peptide-specific CTL induction. Results A total of 16 vaccinations were carried out in six patients. The results were (i no serious adverse effects or DTH reactions, (ii suppression of tumor progression in one patient, (iii increases in the frequency of peptide-specific CTLs in three patients and a decrease in one patient, and (iv successful induction of peptide-specific CTLs from four patients. Conclusions Our findings indicate the safety of the SYT-SSX junction peptide in the use of vaccination and also give support to the property of the peptide to evoke in vivo immunological responses. Modification of both the peptide itself and the related protocol is required to further improve the therapeutic efficacy.

Proteomic profiling of fibroblasts reveals a modulating effect of extracellular calumenin on the organization of the actin cytoskeleton

DEFF Research Database (Denmark)

Jensen, Morten Østergaard; Hansen, Gry Aune; Vorum, Henrik

2006-01-01

cytoskeleton and is involved in cytokinesis. Labeling of S phase fibroblasts with bromo-2'deoxy-uridine indicates that calumenin added to the medium also modulates the cell cycle. Our study thus indicates that calumenin possesses a paracrine role on the cells in its vicinity and therefore may be involved...

Role of human pulmonary fibroblast-derived MCP-1 in cell activation and migration in experimental silicosis

International Nuclear Information System (INIS)

Liu, Xueting; Fang, Shencun; Liu, Haijun; Wang, Xingang; Dai, Xiaoniu; Yin, Qing; Yun, Tianwei; Wang, Wei; Zhang, Yingming; Liao, Hong; Zhang, Wei; Yao, Honghong; Chao, Jie

2015-01-01

Background: Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO 2 ). Phagocytosis of SiO 2 in the lung initiates an inflammatory cascade that results in fibroblast proliferation and migration and subsequent fibrosis. Clinical evidence indicates that the activation of alveolar macrophages by SiO 2 produces rapid and sustained inflammation that is characterized by the generation of monocyte chemotactic protein 1 (MCP-1), which induces fibrosis. Pulmonary fibroblast-derived MCP-1 may play a critical role in fibroblast proliferation and migration. Methods and results: Experiments using primary cultured adult human pulmonary fibroblasts (HPF-a) demonstrated the following results: 1) SiO 2 treatment resulted in the rapid and sustained induction of MCP-1 as well as the elevation of the CC chemokine receptor type 2 (CCR2) protein levels; 2) pretreatment of HPF-a with RS-102895, a specific CCR2 inhibitor, abolished the SiO 2 -induced increase in cell activation and migration in both 2D and 3D culture systems; and 3) RNA interference targeting CCR2 prevented the SiO 2 -induced increase in cell migration. Conclusion: These data demonstrated that the up-regulation of pulmonary fibroblast-derived MCP-1 is involved in pulmonary fibroblast migration induced by SiO 2 . CCR2 was also up-regulated in response to SiO 2 , and this up-regulation facilitated the effect of MCP-1 on fibroblasts. Our study deciphered the link between fibroblast-derived MCP-1 and SiO 2 -induced cell migration. This finding provides novel insight into the potential of MCP-1 in the development of novel therapeutic strategies for silicosis. - Highlights: • Role of pulmonary fibroblast-derived MCP-1 in experimental silicosis was studied. • SiO 2 induced MCP-1 release from cultured human pulmonary fibroblast (HPF-a). • SiO 2 directly activated HPF-a via the MCP-1/CCR2 pathway. • SiO 2 increased HPF-a migration in both 2D and 3D model via the MCP-1/CCR2 pathway. • RNA-i of MCP-1/CCR2

Role of human pulmonary fibroblast-derived MCP-1 in cell activation and migration in experimental silicosis

Energy Technology Data Exchange (ETDEWEB)

Liu, Xueting [Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009 (China); Fang, Shencun [Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 210029 (China); Liu, Haijun [Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing, Jiangsu 210009 (China); Wang, Xingang; Dai, Xiaoniu; Yin, Qing; Yun, Tianwei [Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009 (China); Wang, Wei; Zhang, Yingming [Nine Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing, Jiangsu 210029 (China); Liao, Hong [Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing, Jiangsu 210009 (China); Zhang, Wei [Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009 (China); Yao, Honghong [Department of Pharmacology, Medical School of Southeast University, Nanjing, Jiangsu 210009 (China); Chao, Jie, E-mail: chaojie@seu.edu.cn [Department of Physiology, Medical School of Southeast University, Nanjing, Jiangsu 210009 (China)

2015-10-15

Background: Silicosis is a systemic disease caused by inhaling silicon dioxide (SiO{sub 2}). Phagocytosis of SiO{sub 2} in the lung initiates an inflammatory cascade that results in fibroblast proliferation and migration and subsequent fibrosis. Clinical evidence indicates that the activation of alveolar macrophages by SiO{sub 2} produces rapid and sustained inflammation that is characterized by the generation of monocyte chemotactic protein 1 (MCP-1), which induces fibrosis. Pulmonary fibroblast-derived MCP-1 may play a critical role in fibroblast proliferation and migration. Methods and results: Experiments using primary cultured adult human pulmonary fibroblasts (HPF-a) demonstrated the following results: 1) SiO{sub 2} treatment resulted in the rapid and sustained induction of MCP-1 as well as the elevation of the CC chemokine receptor type 2 (CCR2) protein levels; 2) pretreatment of HPF-a with RS-102895, a specific CCR2 inhibitor, abolished the SiO{sub 2}-induced increase in cell activation and migration in both 2D and 3D culture systems; and 3) RNA interference targeting CCR2 prevented the SiO{sub 2}-induced increase in cell migration. Conclusion: These data demonstrated that the up-regulation of pulmonary fibroblast-derived MCP-1 is involved in pulmonary fibroblast migration induced by SiO{sub 2}. CCR2 was also up-regulated in response to SiO{sub 2}, and this up-regulation facilitated the effect of MCP-1 on fibroblasts. Our study deciphered the link between fibroblast-derived MCP-1 and SiO{sub 2}-induced cell migration. This finding provides novel insight into the potential of MCP-1 in the development of novel therapeutic strategies for silicosis. - Highlights: • Role of pulmonary fibroblast-derived MCP-1 in experimental silicosis was studied. • SiO{sub 2} induced MCP-1 release from cultured human pulmonary fibroblast (HPF-a). • SiO{sub 2} directly activated HPF-a via the MCP-1/CCR2 pathway. • SiO{sub 2} increased HPF-a migration in both 2D and 3D

Cellular sensitivity and low dose-rate recovery in Fanconi anaemia fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Burnet, N.G.; Wurm, R.; Tait, D.M.; Peacock, J.H. (Institute of Cancer Research, Sutton (United Kingdom). Surrey Branch Royal Marsden Hospital, Sutton (United Kingdom))

1994-06-01

Fanconi anaemia (FA) is a rare inherited condition characterized by developmental abnormalities and progressive bone marrow failure, which requires bone marrow transplantation for successful treatment. This involves the use of alkylating agents and total body or thoraco-abdominal irradiation. Both chemical clastogens and irradiation cause increased chromosome damage in FA cells compared with controls. In some studies FA fibroblasts have been found to be more radiosensitive than normal. From these data it has been inferred that patients with FA might be more sensitive than normal to radiotherapy. However, increased radiosensitivity of FA fibroblasts has not been a uniform finding. The radiosensitivity of fibroblasts from two FA patients was studied at high and low dose-rate (LDR), and their sensitivity compared with normal strains. Both FA strains fell at the sensitive end of the range, but both demonstrated marked dose-rate sparing, with D[sub 0.01] recovery factors of 1.23 and 1.27, similar to the normal strains. These recovery factors are inconsistent with the suggestion that FA patients are recovery deficient. The data indicate that at least some FA strains are capable of LDR recovery, and imply that these patients would probably have a clinical benefit from fractionated or low dose-rate total body irradiation. (Author).

Cellular sensitivity and low dose-rate recovery in Fanconi anaemia fibroblasts

International Nuclear Information System (INIS)

Burnet, N.G.; Wurm, R.; Tait, D.M.; Peacock, J.H.

1994-01-01

Fanconi anaemia (FA) is a rare inherited condition characterized by developmental abnormalities and progressive bone marrow failure, which requires bone marrow transplantation for successful treatment. This involves the use of alkylating agents and total body or thoraco-abdominal irradiation. Both chemical clastogens and irradiation cause increased chromosome damage in FA cells compared with controls. In some studies FA fibroblasts have been found to be more radiosensitive than normal. From these data it has been inferred that patients with FA might be more sensitive than normal to radiotherapy. However, increased radiosensitivity of FA fibroblasts has not been a uniform finding. The radiosensitivity of fibroblasts from two FA patients was studied at high and low dose-rate (LDR), and their sensitivity compared with normal strains. Both FA strains fell at the sensitive end of the range, but both demonstrated marked dose-rate sparing, with D 0.01 recovery factors of 1.23 and 1.27, similar to the normal strains. These recovery factors are inconsistent with the suggestion that FA patients are recovery deficient. The data indicate that at least some FA strains are capable of LDR recovery, and imply that these patients would probably have a clinical benefit from fractionated or low dose-rate total body irradiation. (Author)

Chromosome aberration induction in human diploid fibroblast and epithelial cells

International Nuclear Information System (INIS)

Scott, D.

1986-01-01

The relative sensitivity of cultured human fibroblasts and epithelial cells to radiation-induced chromosomal aberrations was investigated. Lung fibroblast and kidney epithelial cells from the same fetus were compared, as were skin fibroblasts and epithelial keratinocytes from the same foreskin sample. After exposure of proliferating fetal cells to 1.5 Gy X-rays there was a very similar aberration yield in the fibroblasts and epithelial cells. Observations of either little or no difference in chromosomal sensitivity between human fibroblasts and epithelial cells give added confidence that quantitative cytogenetic data obtained from cultured fibroblasts are relevant to the question of sensitivity of epithelial cells which are the predominant cell type in human cancers. (author)

Application of 198Au colloid in the treatment of chronic knee synovial effusions

International Nuclear Information System (INIS)

Buril, J.; Zak, J.

1979-01-01

25 cases of chronic synovial exudates of the knee joint were treated with the use of 198 Au colloid (5mCi). Improvement was noted in two thirds of the patients after different numbers of applications (one to five). No improvement was seen in four cases of progressive polyarthritis or in two patients with gonarthrosis. This was to be expected though the number of the cases of the disease treated was very low. (author)

Chlamydia pecorum in Joint Tissue and Synovial Fluid of a Koala ( Phascolarctos cinereus) with Arthritis.

Science.gov (United States)

Burnard, Delaney; Gillett, Amber; Polkinghorne, Adam

2018-03-02

A small number of koalas ( Phascolarctos cinereus) presented to wildlife hospitals in Queensland, Australia, with signs of arthritis in one or more joints. Molecular analysis identified Chlamydia pecorum in the tarsal tissue and synovial fluid of an affected joint of a koala, suggesting that in addition to livestock, C. pecorum has the potential to cause arthritis in the koala.

Disposition of isoflupredone acetate in plasma, urine and synovial fluid following intra-articular administration to exercised Thoroughbred horses.

Science.gov (United States)

Knych, Heather K; Harrison, Linda M; White, Alexandria; McKemie, Daniel S

2016-01-01

The use of isoflupredone acetate in performance horses and the scarcity of published pharmacokinetic data necessitate further study. The objective of the current study was to describe the plasma pharmacokinetics of isoflupredone acetate as well as time-related urine and synovial fluid concentrations following intra-articular administration to horses. Twelve racing-fit adult Thoroughbred horses received a single intra-articular administration (8 mg) of isoflupredone acetate into the right antebrachiocarpal joint. Blood, urine and synovial fluid samples were collected prior to and at various times up to 28 days post drug administration. All samples were analyzed using liquid chromatography-Mass Spectrometry. Plasma data were analyzed using a population pharmacokinetic compartmental model. Maximum measured plasma isoflupredone concentrations were 1.76 ± 0.526 ng/mL at 4.0 ± 1.31 h and 1.63 ± 0.243 ng/mL at 4.75 ± 0.5 h, respectively, for horses that had synovial fluid collected and for those that did not. The plasma beta half-life was 24.2 h. Isoflupredone concentrations were below the limit of detection in all horses by 48 h and 7 days in plasma and urine, respectively. Isoflupredone was detected in the right antebrachiocarpal and middle carpal joints for 8.38 ± 5.21 and 2.38 ± 0.52 days, respectively. Results of this study provide information that can be used to regulate the use of intra-articular isoflupredone in the horse. Copyright © 2015 John Wiley & Sons, Ltd.

The pathogenesis of rheumatoid arthritis in radiological studies. Part I: Formation of inflammatory infiltrates within the synovial membrane

Directory of Open Access Journals (Sweden)

Iwona Sudoł‑Szopińska

2012-06-01

Full Text Available Rheumatoid arthritis is a chronic inflammatory disease with a multifactorial etiology and varied course, which in the majority of patients leads to partial disability or to permanent handicap. Its characteristic trait is a persistent inflammation of the synovial membrane and the formation of an invasive synovial tissue, called the pannus, which in time leads to destruction of the cartilage, subchondral bone tissue, and the soft tissue of the affected joint(s. The pathogenesis of rheumatoid arthritis is complex and involves cells of both innate and adaptive immunity, a network of various cytokines and an immunoregulatory dysfunction. An important role in the discovery of rheumatoid arthritis pathogenesis was played by magnetic resonance imaging, which showed the disease process to extend beyond the synovium into the bone marrow. Many studies have shown a strict correlation between the vascularity of the synovium (assessed through the power Doppler ultrasound and magnetic resonance examinations, bone marrow edema and the clinical, laboratory and histopathological parameters of rheumatoid arthritis. From the current understanding of rheumatoid arthritis, bone erosions could occur from two directions: from the joint cavity and from the bone marrow. With power Doppler ultrasound, as well as in magnetic resonance imaging, it is possible to visualize the well-vascularized pannus and its destructive effects on joint structures and ligaments. In addition, the magnetic resonance study shows inflammatory and destructive changes within the bone marrow (bone marrow edema, inflammatory cysts, and erosions. Bone marrow edema occurs in 68–75% of patients with early rheumatoid arthritis and is considered to be a predictor of rapid disease progression.

Fibrosis in connective tissue disease: the role of the myofibroblast and fibroblast-epithelial cell interactions

Science.gov (United States)

Krieg, Thomas; Abraham, David; Lafyatis, Robert

2007-01-01

Fibrosis, characterized by excessive extracellular matrix accumulation, is a common feature of many connective tissue diseases, notably scleroderma (systemic sclerosis). Experimental studies suggest that a complex network of intercellular interactions involving endothelial cells, epithelial cells, fibroblasts and immune cells, using an array of molecular mediators, drives the pathogenic events that lead to fibrosis. Transforming growth factor-β and endothelin-1, which are part of a cytokine hierarchy with connective tissue growth factor, are key mediators of fibrogenesis and are primarily responsible for the differentiation of fibroblasts toward a myofibroblast phenotype. The tight skin mouse (Tsk-1) model of cutaneous fibrosis suggests that numerous other genes may also be important. PMID:17767742

Synovial sarcoma of the foot; Synovialsarkom des Fusses

Energy Technology Data Exchange (ETDEWEB)

Beus, J. [Mainz Univ. (Germany). Klinik und Poliklinik fuer Radiologie; Kreitner, K.F. [Mainz Univ. (Germany). Klinik und Poliklinik fuer Radiologie; Rompe, J.D. [Mainz Univ. (Germany). Klinik und Poliklinik fuer Orthopaedie; Riehle, H.M. [Mainz Univ. (Germany). Inst. fuer Pathologie

1996-09-01

The case of a 29 year-old female patient who had experienced pain in the right midfoot for 5 years which was diagnosed as a degenerative or rheumatic change and treated by physiotherapy and medication. By means of magnetic resonance imaging we identified a soft-tissue tumor of the midfoot. Histology provided the findings of a monophasic fibrous synovial sarcoma. The case history is reported together with a presentation of the disease and its radiological diagnosis. (orig.) [Deutsch] Es wird ueber den Fall einer 29jaehrigen Patientin berichtet, die 5 Jahre lang wegen Schmerzen im rechten Mittelfuss unter der Diagnose degenerativer oder rheumatischer Veraenderungen physikalisch und medikamentoes behandelt wurde. Magnetresonanztomographisch wurde ein Weichteiltumor des Mittelfusses diagnostiziert. Die histologische Untersuchung erbrachte den Befund eines monophasisch-fibroesen Synovialsarkoms. Mit der Kasuistik verbunden ist eine Darstellung des Krankheitsbildes und dessen radiologischer Diagnostik. (orig.)

Rosmarinic acid potentiates carnosic acid induced apoptosis in lung fibroblasts.

Directory of Open Access Journals (Sweden)

Sana Bahri

Full Text Available Pulmonary fibrosis is characterized by over-population and excessive activation of fibroblasts and myofibroblasts disrupting normal lung structure and functioning. Rosemary extract rich in carnosic acid (CA and rosmarinic acid (RA was reported to cure bleomycin-(BLM-induced pulmonary fibrosis. We demonstrate that CA decreased human lung fibroblast (HLF viability with IC50 value of 17.13±1.06 μM, while RA had no cytotoxic effect. In the presence of 50 μM of RA, dose-response for CA shifted to IC50 value of 11.70±1.46 μM, indicating synergic action. TGFβ-transformed HLF, rat lung fibroblasts and L929 cells presented similar sensitivity to CA and CA+RA (20μM+100μM, respectively treatment. Rat alveolar epithelial cells died only under CA+RA treatment, while A549 cells were not affected. Annexin V staining and DNA quantification suggested that HLF are arrested in G0/G1 cell cycle phase and undergo apoptosis. CA caused sustained activation of phospho-Akt and phospho-p38 expression and inhibition of p21 protein.Addition of RA potentiated these effects, while RA added alone had no action.Only triple combination of inhibitors (MAPK-p38, pan-caspase, PI3K/Akt/autophagy partially attenuated apoptosis; this suggests that cytotoxicity of CA+RA treatment has a complex mechanism involving several parallel signaling pathways. The in vivo antifibrotic effect of CA and RA was compared with that of Vitamine-E in BLM-induced fibrosis model in rats. We found comparable reduction in fibrosis score by CA, RA and CA+RA, attenuation of collagen deposition and normalization of oxidative stress markers. In conclusion, antifibrotic effect of CA+RA is due to synergistic pro-apoptotic action on lung fibroblasts and myofibroblasts.

Regulation and inhibition of collagenase expression by long-wavelength ultraviolet radiation in cultured human skin fibroblasts

International Nuclear Information System (INIS)

Petersen, Marta; Hamilton, Tiffani; Haili Li

1995-01-01

The cellular mechanisms responsible for the connective tissue changes produced by chronic exposure to UV light are poorly understood. collagenase, a metalloproteinase, initiates degradation of types I and III collagen and thus plays a key role in the remodeling of dermal collagen. Collagenase synthesis by fibroblasts and keratinocytes involves the protein kinase C (PKC) second messenger system, and corticosteroids have been shown to suppress its synthesis at the level of gene transcription. Long-wavelength UV light (UVA, 320-400 nm) stimulates the synthesis of interstitial collagenase, as well as increasing PKC activity, in human skin fibroblasts in vitro. This study explores the regulation of collagenase expression by UVA in cultured human skin fibroblasts. Specifically, the time course, the effect of actinomycin D, an inhibitor of RNA synthesis, as well as the effect of PKC inhibitors and dexamethansone on expression of collagenase following UVA irradiation were examined. (Author)

Doubling potential of fibroblasts from different species after ionising radiation

International Nuclear Information System (INIS)

Macieira-Coelho, A.; Diatloff, C.; Malaise, E.

1976-01-01

It is stated that whereas chicken fibroblasts invariably die after a certain number of doublings in vitro, and this fact is never altered by chemical or physical agents, mouse fibroblasts invariably acquire spontaneously an infinite growth potential. In the human species fibroblasts never acquire spontaneously the capacity to divide for ever, although they can become permanent cell lines after treatment with certain viruses. This behaviour of fibroblasts in vitro has been attributed to different nutritional requirements. Experiments are described with human and mouse fibroblasts in which it was found that the response to ionising radiation matches the relative tendencies of the fibroblasts to yield permanent cell lines. Irradiation was commenced during the phase of active proliferation. Human fibroblast cultures irradiated with 100 R stopped dividing earlier than the controls, whereas cultures irradiated with 200, 300 and 500 R had the same lifespan as the control cultures. Cultures irradiated with 400 R showed the longest survival. With mouse fibroblasts the growth curves of the irradiated cells were of the same type as in the controls, but recovery occurred earlier. The results indicated that ionising radiation accelerates a natural phenomenon; in cells with a limited growth potential (chicken) it shortens the lifespan, whereas in cells that can acquire an unlimited growth potential (mouse) it accelerates acquisition of this potential; human fibroblasts showed an intermediate response, since ionising radiation neither established the cultures as with mouse cells nor reduced the number of cells produced as with chicken fibroblasts. Possible explanations for the different behaviour of the species are offered. (U.K.)

Multifaced Roles of the αvβ3 Integrin in Ehlers–Danlos and Arterial Tortuosity Syndromes’ Dermal Fibroblasts

Directory of Open Access Journals (Sweden)

Nicoletta Zoppi

2018-03-01

Full Text Available The αvβ3 integrin, an endothelial cells’ receptor-binding fibronectin (FN in the extracellular matrix (ECM of blood vessels, regulates ECM remodeling during migration, invasion, angiogenesis, wound healing and inflammation, and is also involved in the epithelial mesenchymal transition. In vitro-grown human control fibroblasts organize a fibrillar network of FN, which is preferentially bound on the entire cell surface to its canonical α5β1 integrin receptor, whereas the αvβ3 integrin is present only in rare patches in focal contacts. We report on the preferential recruitment of the αvβ3 integrin, due to the lack of FN–ECM and its canonical integrin receptor, in dermal fibroblasts from Ehlers–Danlos syndromes (EDS and arterial tortuosity syndrome (ATS, which are rare multisystem connective tissue disorders. We review our previous findings that unraveled different biological mechanisms elicited by the αvβ3 integrin in fibroblasts derived from patients affected with classical (cEDS, vascular (vEDS, hypermobile EDS (hEDS, hypermobility spectrum disorders (HSD, and ATS. In cEDS and vEDS, respectively, due to defective type V and type III collagens, αvβ3 rescues patients’ fibroblasts from anoikis through a paxillin-p60Src-mediated cross-talk with the EGF receptor. In hEDS and HSD, without a defined molecular basis, the αvβ3 integrin transduces to the ILK-Snail1-axis inducing a fibroblast-to-myofibroblast-transition. In ATS cells, the deficiency of the dehydroascorbic acid transporter GLUT10 leads to redox imbalance, ECM disarray together with the activation of a non-canonical αvβ3 integrin-TGFBRII signaling, involving p125FAK/p60Src/p38MAPK. The characterization of these different biological functions triggered by αvβ3 provides insights into the multifaced nature of this integrin, at least in cultured dermal fibroblasts, offering future perspectives for research in this field.

Correlation of prostaglandin E2 concentrations in synovial fluid with ground reaction forces and clinical variables for pain or inflammation in dogs with osteoarthritis induced by transection of the cranial cruciate ligament.

Science.gov (United States)

Trumble, Troy N; Billinghurst, R Clark; McIlwraith, C Wayne

2004-09-01

To evaluate the temporal pattern of prostaglandin (PG) E2 concentrations in synovial fluid after transection of the cranial cruciate ligament (CCL) in dogs and to correlate PGE2 concentrations with ground reaction forces and subjective clinical variables for lameness or pain. 19 purpose-bred adult male Walker Hounds. Force plate measurements, subjective clinical analysis of pain or lameness, and samples of synovial fluid were obtained before (baseline) and at various time points after arthroscopic transection of the right CCL. Concentrations of PGE2 were measured in synovial fluid samples, and the PGE2 concentrations were correlated with ground reaction forces and clinical variables. The PGE2 concentration increased significantly above the baseline value throughout the entire study, peaking 14 days after transection. Peak vertical force and vertical impulse significantly decreased by day 14 after transection, followed by an increase over time without returning to baseline values. All clinical variables (eg, lameness, degree of weight bearing, joint extension, cumulative pain score, effusion score, and total protein content of synovial fluid, except for WBC count in synovial fluid) increased significantly above baseline values. Significant negative correlations were detected between PGE2 concentrations and peak vertical force (r, -0.5720) and vertical impulse (r, -0.4618), and significant positive correlations were detected between PGE2 concentrations and the subjective lameness score (r, 0.5016) and effusion score (r, 0.6817). Assessment of the acute inflammatory process by measurement of PGE2 concentrations in synovial fluid may be correlated with the amount of pain or lameness in dogs.

Tumor-secreted LOXL2 activates fibroblasts through FAK signaling

DEFF Research Database (Denmark)

Barker, Holly E; Bird, Demelza; Lang, Georgina

2013-01-01

models. Here, we discovered that tumor-derived LOXL2 directly activated stromal fibroblasts in the tumor microenvironment. Genetic manipulation or antibody inhibition of LOXL2 in orthotopically grown mammary tumors reduced the expression of α-smooth muscle actin (α-SMA). Using a marker for reticular....... Importantly, in vitro assays revealed that tumor-derived LOXL2 and a recombinant LOXL2 protein induced fibroblast branching on collagen matrices, as well as increased fibroblast-mediated collagen contraction and invasion of fibroblasts through extracellular matrix. Moreover, LOXL2 induced the expression of α...

Phenotype change and migration of adventitial fibroblasts during postangioplasty

International Nuclear Information System (INIS)

Wang Yongli; Zhang Jiaxing; He Nengshu; Si Tongguo; Fan Hailun; Ge Xihong; Xu Rui

2006-01-01

Objective: To verify fibroblasts translocation from adventitia into neointima by labeling adventitia cells with bromodeoxyuridine (BrDU) after angioplasty, and to explore the relationship of adventitial fibroblast with restenosis. Methods: Vascular restenosis model was created by injured intima of common carotid artery (CCA) of mouse with guide wire, adventitial fibroblasts were labeled with BrDU, and dynamic distribution of myofibroblasts in adventitia, media and neoitima was observed at different times (3 d, 7 d, 14 d and 28 d) by means of single/double-label immunohistochemistry, light microscope, electronic microscope and image analysis system. Results: 1.Immunohistochemistry: More adventitial fibroblasts combined with BrDU could be found in adventitia on the 3rd day of postangioplasty, and the number of this kind of cells reached the peak on 7th day, and at the same time fibroblasts changed their phenotypes and became myofibroblasts, which produced α-actin and extracellular matrix (ECM). On 14th day, the number of the positive cells decreased in adventitia, increased in media and neointima associated with intima thickening; on 28th day, while the number of fibroblasts labeled by BrDU returned to the basic-line in adventitia, media and intima, nevertheless, intima thickening and vascular stenosis and intimal ELM precipitation were still present. There were significant differences in the number of fibroblasts labeled with BrDU located in three layers of artery (P<0.05). 2. Electronic microscope: After angioplasty, the plasm of fibroblasts became rich, mitochondrious and increase of Golgi apparatus; and the amount of rough endoplasmic reticulums rose with more secretory granules, together with a great amount of collagen synthesized forming the microfilaments; on days of 7th and 14th, the wide pseudopodia of myofibroblasts could be found extending into the windows on the external elastic lamina (ELL) and the internal elastic lamina (ILL); and showing the tendency

Influence of exogenous leptin on redox homeostasis in neutrophils and lymphocytes cultured in synovial fluid isolated from patients with rheumatoid arthritis

Directory of Open Access Journals (Sweden)

Michał Gajewski

2016-07-01

Full Text Available Objectives : Leptin is an adipose cells derived hormone that regulates energy homeostasis within the body. Energy metabolism of immune cells influences their activity within numerous pathological states, but the effect of leptin on these cells in unclear. On the one hand, it was observed that leptin induces neutrophils chemotaxis and modulates phagocytosis. On the other hand, neutrophils exposed to leptin did not display detectable Ca 2+ ions mobilization or β 2 -integrin upregulation. In this study, we investigated the effect of leptin on the redox homeostasis in lymphocytes and neutrophils. Material and methods : Neutrophils and lymphocytes were isolated by density-gradient centrifugation of blood from healthy volunteers. Cells were cultured with or without leptin (100 ng/ml for lymphocytes and 500 ng/ml for neutrophils or with or without synovial fluid (85% for 0–72 h. Culture media were not changed during incubation. Cells were homogenized and homogenate was frozen until laboratory measurements. Redox homeostasis was assessed by the reduced glutathione (GSH vs. oxidized glutathione (GSSG ratio and membrane lipid peroxidation evaluation. Results : Lymphocytes cultured with leptin and synovial fluid showed a significant increase of the GSSG level. The GSSG/GSH ratio increased by 184 ±37%. In neutrophils incubated in a similar environment, the GSSG/GSH ratio increased by just 21 ±7%, and the effect was observed irrespectively of whether they were exposed to leptin or synovial fluid or both together. Neither leptin nor synovial fluid influenced lipid peroxidation in neutrophils, but in lymphocytes leptin intensified lipid peroxidation. Conclusions : Leptin altered the lymphocytes, but not neutrophils redox state. Because firstly neutrophils are anaerobic cells and have just a few mitochondria and secondly lymphocytes have typical aerobic metabolism, the divergence of our data supports the hypothesis that leptin induces oxidative stress by

In vitro invasion and survival of Porphyromonas gingivalis in gingival fibroblasts: role of the capsule

NARCIS (Netherlands)

Irshad, M.; van der Reijden, W.A.; Crielaard, W.; Laine, M.L.

2012-01-01

Porphyromonas gingivalis is a Gram-negative, anaerobic bacterium involved in periodontitis and peri-implantitis that can invade and survive inside host cells in vitro. P. gingivalis can invade human gingival fibroblasts (GF), but no data are available about the role of P. gingivalis’ capsule in GF

Analysis of the levels of endotoxin and β-d-glucan in the synovial fluid of hemodialysis patients.

Science.gov (United States)

Shiota, E; Maekawa, M; Kono, T

2001-12-01

Abstract We analyzed the levels of endotoxin and β-d-glucan, which possibly induce cytokine production, in the synovial fluid of patients on long-term hemodialysis and compared the results to those in patients with osteoarthritis and rheumatoid arthritis. We studied 42 knees in 42 hemodialysis patients, 21 in 21 osteoarthritis patients, and 26 in 26 rheumatoid arthritis patients. The mean ages were 60.7, 63.2, and 59.7 years, respectively. The duration of hemodialysis in the long-term hemodialysis group averaged 14.0 years. The concentrations of endotoxin and β-d-glucan in the synovial fluid of these three groups were measured. The concentration of endotoxin was the same in the three groups. However, the concentration of β-d-glucan was significantly higher in long-term hemodialysis patients. This finding suggests that β-d-glucan may have some relation to the pathogenesis of the synovitis which exists in the hydrarthrosis of long-term hemodialysis patients.

Kallikrein-related peptidase 4 induces cancer-associated fibroblast features in prostate-derived stromal cells.

Science.gov (United States)

Kryza, Thomas; Silva, Lakmali M; Bock, Nathalie; Fuhrman-Luck, Ruth A; Stephens, Carson R; Gao, Jin; Samaratunga, Hema; Lawrence, Mitchell G; Hooper, John D; Dong, Ying; Risbridger, Gail P; Clements, Judith A

2017-10-01

The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer-associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intraepithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peristromal interface. KLK4 induced CAF-like features in the prostate-derived WPMY1 normal stromal cell line, including increased expression of alpha-smooth muscle actin, ESR1 and SFRP1. KLK4 activated protease-activated receptor-1 in WPMY1 cells increasing expression of several factors (FGF1, TAGLN, LOX, IL8, VEGFA) involved in prostate cancer progression. In addition, KLK4 induced WPMY1 cell proliferation and secretome changes, which in turn stimulated HUVEC cell proliferation that could be blocked by a VEGFA antibody. Importantly, the genes dysregulated by KLK4 treatment of WPMY1 cells were also differentially expressed between patient-derived CAFs compared to matched nonmalignant fibroblasts and were further increased by KLK4 treatment. Taken together, we propose that epithelial-derived KLK4 promotes tumour progression by actively promoting CAF differentiation in the prostate stromal microenvironment. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Curcumin attenuates inflammatory response in IL-1beta-induced human synovial fibroblasts and collagen-induced arthritis in mouse model.

Science.gov (United States)

Moon, Dong-Oh; Kim, Mun-Ok; Choi, Yung Hyun; Park, Yung-Min; Kim, Gi-Young

2010-05-01

Curcumin, a major component of turmeric, has been shown to exhibit anti-oxidant and anti-inflammatory activities. The present study was performed to determine whether curcumin is efficacious against both collagen-induced arthritis (CIA) in mice and IL-1beta-induced activation in fibroblast-like synoviocytes (FLSs). DBA/1 mice were immunized with bovine type II collagen (CII) and treated with curcumin every other day for 2weeks after the initial immunization. For arthritis, we evaluated the incidence of disease and used an arthritis index based on paw thickness. In vitro proliferation of CII- or concanavalin A-induced splenic T cells was examined using IFN-gamma production. Pro-inflammatory cytokines TNF-alpha and IL-1beta were examined in the mouse ankle joint and serum IgG1 and IgG2a isotypes were analyzed. The expression levels of prostaglandin E(2) (PGE(2)), cyclooxygenase-2 (COX-2), and matrix metalloproteinases (MMPs) in human FLSs were also determined. The results showed that compared with untreated CIA mice, curcumin-treated mice downregulated clinical arthritis score, the proliferation of splenic T cells, expression levels of TNF-alpha and IL-1beta in the ankle joint, and expression levels of IgG2a in serum. Additionally, by altering nuclear factor (NF)-kappaB transcription activity in FLSs, curcumin inhibited PGE(2) production, COX-2 expression, and MMP secretion. These results suggest that curcumin can effectively suppress inflammatory response by inhibiting pro-inflammatory mediators and regulating humoral and cellular immune responses. Copyright 2010 Elsevier B.V. All rights reserved.

Quantitative magnetic resonance imaging as marker of synovial membrane regeneration and recurrence of synovitis after arthroscopic knee joint synovectomy: a one year follow up study

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Østergaard, Mikkel; Ejbjerg, B; Stoltenberg, M

2001-01-01

OBJECTIVES: By repeated magnetic resonance imaging (MRI) to study synovial membrane regeneration and recurrence of synovitis after arthroscopic knee joint synovectomy in patients with rheumatoid arthritis (RA) and other (non-RA) causes of persistent knee joint synovitis. METHODS: Contrast enhanced...... at two months. No significant differences between volumes in RA and non-RA knees were seen. Synovial membrane volumes at two months were significantly inversely correlated with the duration of clinical remission, for all knees considered together (Spearman's correlation r(s)=-0.67; p

Histopathological Analysis of PEEK Wear Particle Effects on the Synovial Tissue of Patients

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Jansson, V.; Giurea, A.

2016-01-01

Introduction. Increasing interest developed in the use of carbon-fiber-reinforced-poly-ether-ether-ketones (CFR-PEEK) as an alternative bearing material in knee arthroplasty. The effects of CFR-PEEK wear in in vitro and animal studies are controversially discussed, as there are no data available concerning human tissue. The aim of this study was to analyze human tissue containing CFR-PEEK as well as UHMWPE wear debris. The authors hypothesized no difference between the used biomaterials. Methods and Materials. In 10 patients during knee revision surgery of a rotating-hinge-knee-implant-design, synovial tissue samples were achieved (tibial inserts: UHMWPE; bushings and flanges: CFR-PEEK). One additional patient received revision surgery without any PEEK components as a control. The tissue was paraffin-embedded, sliced into 2 μm thick sections, and stained with hematoxylin and eosin in a standard process. A modified panoptical staining was also done. Results. A “wear-type” reaction was seen in the testing and the control group. In all samples, the UHMWPE particles were scattered in the tissue or incorporated in giant cells. CFR-PEEK particles were seen as conglomerates and only could be found next to vessels. CFR-PEEK particles showed no giant-cell reactions. In conclusion, the hypothesis has to be rejected. UHMWPE and PEEK showed a different scatter-behavior in human synovial tissue. PMID:27766256

LXA{sub 4} actions direct fibroblast function and wound closure

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Herrera, Bruno S. [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States); Microbiology Branch, US Army Dental and Trauma Research Detachment, Institute of Surgical Research, JBSA Fort Sam Houston, TX (United States); Kantarci, Alpdogan; Zarrough, Ahmed; Hasturk, Hatice [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States); Leung, Kai P., E-mail: kai.p.leung.civ@mail.mil [Microbiology Branch, US Army Dental and Trauma Research Detachment, Institute of Surgical Research, JBSA Fort Sam Houston, TX (United States); Van Dyke, Thomas E., E-mail: tvandyke@forsyth.org [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States)

2015-09-04

Timely resolution of inflammation is crucial for normal wound healing. Resolution of inflammation is an active biological process regulated by specialized lipid mediators including the lipoxins and resolvins. Failure of resolution activity has a major negative impact on wound healing in chronic inflammatory diseases that is manifest as excess fibrosis and scarring. Lipoxins, including Lipoxin A{sub 4} (LXA{sub 4}), have known anti-fibrotic and anti-scarring properties. The goal of this study was to elucidate the impact of LXA{sub 4} on fibroblast function. Mouse fibroblasts (3T3 Mus musculus Swiss) were cultured for 72 h in the presence of TGF-β1, to induce fibroblast activation. The impact of exogenous TGF-β1 (1 ng/mL) on LXA{sub 4} receptor expression (ALX/FPR2) was determined by flow cytometry. Fibroblast proliferation was measured by bromodeoxyuridine (BrdU) labeling and migration in a “scratch” assay wound model. Expression of α-smooth muscle actin (α-SMA), and collagen types I and III were measured by Western blot. We observed that TGF-β1 up-regulates LXA{sub 4} receptor expression, enhances fibroblast proliferation, migration and scratch wound closure. α-SMA levels and Collagen type I and III deposition were also enhanced. LXA{sub 4} slowed fibroblast migration and scratch wound closure at early time points (24 h), but wound closure was equal to TGF-β1 alone at 48 and 72 h. LXA{sub 4} tended to slow fibroblast proliferation at both concentrations, but had no impact on α-SMA or collagen production by TGF-β1 stimulated fibroblasts. The generalizability of the actions of resolution molecules was examined in experiments repeated with resolvin D2 (RvD2) as the agonist. The activity of RvD2 mimicked the actions of LXA{sub 4} in all assays, through an as yet unidentified receptor. The results suggest that mediators of resolution of inflammation enhance wound healing and limit fibrosis in part by modulating fibroblast function. - Highlights: • TGF

Viability test of fish scale collagen (Oshpronemus gouramy on baby hamster kidney fibroblasts-21 fibroblast cell culture

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Chiquita Prahasanti

2018-04-01

Full Text Available Aim: This study aims to examine the toxicity of collagen extracted from gouramy fish scales (Oshpronemus gouramy by evaluating its viability against baby hamster kidney fibroblasts-21. Materials and Methods: Collagen was extracted from gouramy fish scales (O. gouramy with 6% acetic acid. Its results were analyzed using Fourier-transform infrared spectroscopy and freeze-dried technique. Its morphology then was analyzed with scanning electron microscope. Afterward, 3-(4.5-dimethylthiazole-2-yl2.5-diphenyl tetrazolium bromide assay was conducted to compare cells with and without fish scale collagen treatment. Results: Collagen extracted from gouramy fish scales had no influence statistically on cultured fibroblast cells with a statistical significance (2-tailed value of 0.754 (p>00025. Conclusion: Collagen extracted from gouramy fish scales has high viability against BHK21 fibroblast cells.

Extracellular matrix organization modulates fibroblast growth and growth factor responsiveness.

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Nakagawa, S; Pawelek, P; Grinnell, F

1989-06-01

To learn more about the relationship between extracellular matrix organization, cell shape, and cell growth control, we studied DNA synthesis by fibroblasts in collagen gels that were either attached to culture dishes or floating in culture medium during gel contraction. After 4 days of contraction, the collagen density (initially 1.5 mg/ml) reached 22 mg/ml in attached gels and 55 mg/ml in floating gels. After contraction, attached collagen gels were well organized; collagen fibrils were aligned in the plane of cell spreading; and fibroblasts had an elongated, bipolar morphology. Floating collagen gels, however, were unorganized; collagen fibrils were arranged randomly; and fibroblasts had a stellate morphology. DNA synthesis by fibroblasts in contracted collagen gels was suppressed if the gels were floating in medium but not if the gels were attached, and inhibition was independent of the extent of gel contraction. Therefore, growth of fibroblasts in contracted collagen gels could be regulated by differences in extracellular matrix organization and cell shape independently of extracellular matrix density. We also compared the responses of fibroblasts in contracted collagen gels and monolayer culture to peptide growth factors including fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, and interleukin 1. Cells in floating collagen gels were generally unresponsive to any of the growth factors. Cells in attached collagen gels and monolayer culture were affected similarly by fibroblast growth factor but not by the others. Our results indicate that extracellular matrix organization influenced not only cell growth, but also fibroblast responsiveness to peptide growth factors.

Extracellular ATP drives breast cancer cell migration and metastasis via S100A4 production by cancer cells and fibroblasts.

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Liu, Ying; Geng, Yue-Hang; Yang, Hui; Yang, Han; Zhou, Yan-Ting; Zhang, Hong-Quan; Tian, Xin-Xia; Fang, Wei-Gang

2018-05-04

Our previous work has demonstrated that extracellular ATP is an important pro-invasive factor, and in this study, we tapped into a possible mechanism involved. We discovered that ATP could upregulate both the intracellular expression and secretion of S100A4 in breast cancer cells and fibroblasts. Apart from stimulating breast cancer cell motility via intracellular S100A4, ATP enhanced the ability of breast cancer cells to transform fibroblasts into cancer-associated fibroblast (CAF)-like cells, which in turn secreted S100A4 to further promote cancer cell motility. Both apyrase and niclosamide treatments could inhibit metastasis of inoculated tumors to lung, liver and kidney in mice model, and CAFs from these treated tumors exhibited weakened migration-stimulating capacity for breast cancer cells. Collectively, our data indicate that extracellular ATP promotes the interactions between breast cancer cells and fibroblasts, which work collaboratively via production of S100A4 to exacerbate breast cancer metastasis. Copyright © 2018. Published by Elsevier B.V.

Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.

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Jaroslaw Suchanski

Full Text Available In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first

Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.

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Suchanski, Jaroslaw; Tejchman, Anna; Zacharski, Maciej; Piotrowska, Aleksandra; Grzegrzolka, Jedrzej; Chodaczek, Grzegorz; Nowinska, Katarzyna; Rys, Janusz; Dziegiel, Piotr; Kieda, Claudine; Ugorski, Maciej

2017-01-01

In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst) overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first time, that such

Serum amyloid A isoforms in serum and synovial fluid from spontaneously diseased dogs with joint diseases or other conditions

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Kjelgaard-Hansen, Mads Jens; Christensen, Michelle B.; Lee, Marcel Huisung

2007-01-01

Serum amyloid A (SAA) is a major acute phase protein in dogs. However, knowledge of qualitative properties of canine SAA and extent of its synthesis in extrahepatic tissues is limited. The aim of the study was to investigate expression of different SAA isoforms in serum and synovial fluid...... in samples obtained from dogs (n = 16) suffering from different inflammatory or non-inflammatory conditions, which were either related or unrelated to joints. Expression of SAA isoforms was visualized by denaturing isoelectric focusing and Western blotting. Serum amyloid A was present in serum from all dogs...... with systemic inflammatory activity, and up to four major isoforms with apparent isoelectric points between 6.1 and 7.9 were identified. In synovial fluid from inflamed joints one or more highly alkaline SAA isoforms (with apparent isoelectric points above 9.3) were identified, with data suggesting local...

The CXC chemokine cCAF stimulates precocious deposition of ECM molecules by wound fibroblasts, accelerating development of granulation tissue

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Li Qi-Jing

2002-06-01

Full Text Available Abstract Background During wound repair, fibroblasts orchestrate replacement of the provisional matrix formed during clotting with tenascin, cellular fibronectin and collagen III. These, in turn, are critical for migration of endothelial cells, keratinocytes and additional fibroblasts into the wound site. Fibroblasts are also important in the deposition of collagen I during scar formation. The CXC chemokine chicken Chemotactic and Angiogenic Factor (cCAF, is highly expressed by fibroblasts after wounding and during development of the granulation tissue, especially in areas where extracellular matrix (ECM is abundant. We hypothesized that cCAF stimulates fibroblasts to produce these matrix molecules. Results Here we show that this chemokine can stimulate precocious deposition of tenascin, fibronectin and collagen I, but not collagen III. Studies in culture and in vivo show that tenascin stimulation can also be achieved by the N-terminal 15 aas of the protein and occurs at the level of gene expression. In contrast, stimulation of fibronectin and collagen I both require the entire molecule and do not involve changes in gene expression. Fibronectin accumulation appears to be linked to tenascin production, and collagen I to decreased MMP-1 levels. In addition, cCAF is chemotactic for fibroblasts and accelerates their migration. Conclusions These previously unknown functions for chemokines suggest that cCAF, the chicken orthologue of human IL-8, enhances healing by rapidly chemoattracting fibroblasts into the wound site and stimulating them to produce ECM molecules, leading to precocious development of granulation tissue. This acceleration of the repair process may have important application to healing of impaired wounds.

Fibroblasts accelerate islet revascularization and improve long-term graft survival in a mouse model of subcutaneous islet transplantation.

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Marcos Perez-Basterrechea

Full Text Available Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors. Our group has developed a model for subcutaneous islet transplantation using a plasma-based scaffold containing fibroblasts as accessory cells that allowed achieving glycemic control in diabetic mice. Transplanted tissue engraftment is critical during the first days after transplantation, thus we have gone in depth into the graft-supporting role of fibroblasts during the first ten days after islet transplantation. All mice transplanted with islets embedded in the plasma-based scaffold reversed hyperglycemia, although long-term glycemic control was maintained only in the group transplanted with the fibroblasts-containing scaffold. By gene expression analysis and histology examination during the first days we could conclude that these differences might be explained by overexpression of genes involved in vessel development as well as in β-cell regeneration that were detected when fibroblasts were present in the graft. Furthermore, fibroblasts presence correlated with a faster graft re-vascularization, a higher insulin-positive area and a lower cell death. Therefore, this work underlines the importance of fibroblasts as accessory cells in islet transplantation, and suggests its possible use in other graft-supporting strategies.

Fibroblasts accelerate islet revascularization and improve long-term graft survival in a mouse model of subcutaneous islet transplantation.

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Perez-Basterrechea, Marcos; Esteban, Manuel Martinez; Alvarez-Viejo, Maria; Fontanil, Tania; Cal, Santiago; Sanchez Pitiot, Marta; Otero, Jesus; Obaya, Alvaro Jesus

2017-01-01

Pancreatic islet transplantation has been considered for many years a promising therapy for beta-cell replacement in patients with type-1 diabetes despite that long-term clinical results are not as satisfactory. This fact points to the necessity of designing strategies to improve and accelerate islets engraftment, paying special attention to events assuring their revascularization. Fibroblasts constitute a cell population that collaborates on tissue homeostasis, keeping the equilibrium between production and degradation of structural components as well as maintaining the required amount of survival factors. Our group has developed a model for subcutaneous islet transplantation using a plasma-based scaffold containing fibroblasts as accessory cells that allowed achieving glycemic control in diabetic mice. Transplanted tissue engraftment is critical during the first days after transplantation, thus we have gone in depth into the graft-supporting role of fibroblasts during the first ten days after islet transplantation. All mice transplanted with islets embedded in the plasma-based scaffold reversed hyperglycemia, although long-term glycemic control was maintained only in the group transplanted with the fibroblasts-containing scaffold. By gene expression analysis and histology examination during the first days we could conclude that these differences might be explained by overexpression of genes involved in vessel development as well as in β-cell regeneration that were detected when fibroblasts were present in the graft. Furthermore, fibroblasts presence correlated with a faster graft re-vascularization, a higher insulin-positive area and a lower cell death. Therefore, this work underlines the importance of fibroblasts as accessory cells in islet transplantation, and suggests its possible use in other graft-supporting strategies.

Synovial CD4+ T-cell-derived GM-CSF supports the differentiation of an inflammatory dendritic cell population in rheumatoid arthritis

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Reynolds, G; Gibbon, J R; Pratt, A G; Wood, M J; Coady, D; Raftery, G; Lorenzi, A R; Gray, A; Filer, A; Buckley, C D; Haniffa, M A; Isaacs, J D; Hilkens, C M U

2016-01-01

Objective A population of synovial inflammatory dendritic cells (infDCs) has recently been identified in rheumatoid arthritis (RA) and is thought to be monocyte-derived. Here, we investigated the role and source of granulocyte macrophage-colony-stimulating factor (GM-CSF) in the differentiation of synovial infDC in RA. Methods Production of GM-CSF by peripheral blood (PB) and synovial fluid (SF) CD4+ T cells was assessed by ELISA and flow cytometry. In vitro CD4+ T-cell polarisation experiments were performed with T-cell activating CD2/CD3/CD28-coated beads in the absence or presence of pro-Th1 or pro-Th17 cytokines. CD1c+ DC and CD16+ macrophage subsets were flow-sorted and analysed morphologically and functionally (T-cell stimulatory/polarising capacity). Results RA-SF CD4+ T cells produced abundant GM-CSF upon stimulation and significantly more than RA-SF mononuclear cells depleted of CD4+ T cells. GM-CSF-producing T cells were significantly increased in RA-SF compared with non-RA inflammatory arthritis SF, active RA PB and healthy donor PB. GM-CSF-producing CD4+ T cells were expanded by Th1-promoting but not Th17-promoting conditions. Following coculture with RA-SF CD4+ T cells, but not healthy donor PB CD4+ T cells, a subpopulation of monocytes differentiated into CD1c+ infDC; a process dependent on GM-CSF. These infDC displayed potent alloproliferative capacity and enhanced GM-CSF, interleukin-17 and interferon-γ production by CD4+ T cells. InfDC with an identical phenotype to in vitro generated cells were significantly enriched in RA-SF compared with non-RA-SF/tissue/PB. Conclusions We demonstrate a therapeutically tractable feedback loop of GM-CSF secreted by RA synovial CD4+ T cells promoting the differentiation of infDC with potent capacity to induce GM-CSF-producing CD4+ T cells. PMID:25923217

Distribution of Podoplanin in Synovial Tissues in Rheumatoid Arthritis Patients Using Biologic or Conventional Disease-Modifying Anti-Rheumatic Drugs.

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Takakubo, Yuya; Oki, Hiroharu; Naganuma, Yasushi; Saski, Kan; Sasaki, Akiko; Tamaki, Yasunobu; Suran, Yang; Konta, Tsuneo; Takagi, Michiaki

2017-01-01

Podoplanin (PDPN) mediates tumor cell migration and invasion, which phenomena might also play a role in severe rheumatoid arthritis (RA). Therefore, the precise cellular distribution of PDPN and it's relationships with inflammation was studied in RA treated with biologic disease-modifying anti-rheumatic drugs (DMARD) or conventional DMARDs (cDMARD). PDPN+ cells were immunostained by NZ-1 mAb, and scored (3+; >50%/ area, 2+; 20%- 50%, 1+; 5%-20%, 0: <5%) in synovial tissues from RA treated with biologic DMARDs (BIO, n=20) or cDMARD (n=20) for comparison with osteoarthritis (OA, n=5), followed by cell grading of inflammation and cell-typing. Inflammatory synovitis score was 1.4 in both BIO and cDMARD, compared to only 0.2 in OA. PDPN+ cells were found in the lining layer (BIO 1.6, cDMARD 1.3, OA 0.2) and lymphoid aggregates (BIO 0.6, cDMRD 0.7, OA 0.2), and correlated with RA-inflammation in BIO- and cDMARD-groups in both area (r=0.7/0.9, r=0.6/0.7, respectively p<0.05). PDPN was expressed in CD68+ type A macrophage-like and 5B5+ type B fibroblast-like cells in the lining layer, and in IL- 17+ cells in lymphoid aggregates in RA. PDPN was markedly increased in the immunologically inflamed RA synovitis, which was surgically treated due to BIO- and cDMARD-resistant RA. PDPN may have potential of a new marker of residual arthritis in local joints for inflammation-associated severe RA. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Sustained Release of Prostaglandin E2 in Fibroblasts Expressing Ectopically Cyclooxygenase 2 Impairs P2Y-Dependent Ca2+-Mobilization

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María Pimentel-Santillana

2014-01-01

Full Text Available The nucleotide uridine trisphosphate (UTP released to the extracellular milieu acts as a signaling molecule via activation of specific pyrimidine receptors (P2Y. P2Y receptors are G protein-coupled receptors expressed in many cell types. These receptors mediate several cell responses and they are involved in intracellular calcium mobilization. We investigated the role of the prostanoid PGE2 in P2Y signaling in mouse embryonic fibroblasts (MEFs, since these cells are involved in different ontogenic and physiopathological processes, among them is tissue repair following proinflammatory activation. Interestingly, Ca2+-mobilization induced by UTP-dependent P2Y activation was reduced by PGE2 when this prostanoid was produced by MEFs transfected with COX-2 or when PGE2 was added exogenously to the culture medium. This Ca2+-mobilization was important for the activation of different metabolic pathways in fibroblasts. Moreover, inhibition of COX-2 with selective coxibs prevented UTP-dependent P2Y activation in these cells. The inhibition of P2Y responses by PGE2 involves the activation of PKCs and PKD, a response that can be suppressed after pharmacological inhibition of these protein kinases. In addition to this, PGE2 reduces the fibroblast migration induced by P2Y-agonists such as UTP. Taken together, these data demonstrate that PGE2 is involved in the regulation of P2Y signaling in these cells.

A reappraisal of hemangiopericytoma of bone; analysis of cases reclassified as synovial sarcoma and solitary fibrous tumor of bone

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Verbeke, Sofie L J; Fletcher, Christopher D M; Alberghini, Marco

2010-01-01

Hemangiopericytoma (HPC) was first described as a neoplasm with distinct morphologic features, presumably composed of pericytes. In soft tissue, it is accepted that most such lesions are solitary fibrous tumors (SFTs), monophasic synovial sarcomas (SSs), or myofibromatoses. It is unclear whether...

Collagen expression in fibroblasts with a novel LMNA mutation

International Nuclear Information System (INIS)

Nguyen, Desiree; Leistritz, Dru F.; Turner, Lesley; MacGregor, David; Ohson, Kamal; Dancey, Paul; Martin, George M.; Oshima, Junko

2007-01-01

Laminopathies are a group of genetic disorders caused by LMNA mutations; they include muscular dystrophies, lipodystrophies, and progeroid syndromes. We identified a novel heterozygous LMNA mutation, L59R, in a patient with the general appearance of mandibuloacral dysplasia and progeroid features. Examination of the nuclei of dermal fibroblasts revealed the irregular morphology characteristic of LMNA mutant cells. The nuclear morphological abnormalities of LMNA mutant lymphoblastoid cell lines were less prominent compared to those of primary fibroblasts. Since it has been reported that progeroid features are associated with increased extracellular matrix in dermal tissues, we compared a subset of these components in fibroblast cultures from LMNA mutants with those of control fibroblasts. There was no evidence of intracellular accumulation or altered mobility of collagen chains, or altered conversion of procollagen to collagen, suggesting that skin fibroblast-mediated matrix production may not play a significant role in the pathogenesis of this particular laminopathy

Merkel Cell Polyomavirus Infection of Animal Dermal Fibroblasts.

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Liu, Wei; Krump, Nathan A; MacDonald, Margo; You, Jianxin

2018-02-15

Merkel cell polyomavirus (MCPyV) is the first polyomavirus to be associated with human cancer. Mechanistic studies attempting to fully elucidate MCPyV's oncogenic mechanisms have been hampered by the lack of animal models for MCPyV infection. In this study, we examined the ability of MCPyV-GFP pseudovirus (containing a green fluorescent protein [GFP] reporter construct), MCPyV recombinant virions, and several MCPyV chimeric viruses to infect dermal fibroblasts isolated from various model animals, including mouse ( Mus musculus ), rabbit ( Oryctolagus cuniculus ), rat ( Rattus norvegicus ), chimpanzee ( Pan troglodytes ), rhesus macaque ( Macaca mulatta ), patas monkey ( Erythrocebus patas ), common woolly monkey ( Lagothrix lagotricha ), red-chested mustached tamarin ( Saguinus labiatus ), and tree shrew ( Tupaia belangeri ). We found that MCPyV-GFP pseudovirus was able to enter the dermal fibroblasts of all species tested. Chimpanzee dermal fibroblasts were the only type that supported vigorous MCPyV gene expression and viral replication, and they did so to a level beyond that of human dermal fibroblasts. We further demonstrated that both human and chimpanzee dermal fibroblasts produce infectious MCPyV virions that can successfully infect new cells. In addition, rat dermal fibroblasts supported robust MCPyV large T antigen expression after infection with an MCPyV chimeric virus in which the entire enhancer region of the MCPyV early promoter has been replaced with the simian virus 40 (SV40) analog. Our results suggest that viral transcription and/or replication events represent the major hurdle for MCPyV cross-species transmission. The capacity of rat dermal fibroblasts to support MCPyV early gene expression suggests that the rat is a candidate model organism for studying viral oncogene function during Merkel cell carcinoma (MCC) oncogenic progression. IMPORTANCE MCPyV plays an important role in the development of a highly aggressive form of skin cancer, Merkel

Concentrations of tylvalosin and 3-O-acetyltylosin attained in the synovial fluid of swine after administration by oral gavage at 50 and 5 mg/kg.

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Canning, P; Bates, J; Hammen, K; Coetzee, J; Wulf, L; Rajewski, S; Wang, C; Karriker, L

2016-12-01

The objectives of this study were to determine the concentration of tylvalosin (TVN) and its metabolite, 3-O-acetyltylosin (3AT) in the synovial fluid of growing pigs when administered as a single bolus by oral gavage at target doses of 50 mg/kg (Trial 1) and 5 mg/kg (Trial 2). TVN is a water soluble macrolide antimicrobial used in swine production. The stability of the drug in synovial fluid samples stored at -70 °C up to 28 days was also evaluated in Trial 2. In Trial 1, eight pigs were randomly assigned to one of eight time points for euthanasia and synovial fluid collection: 0, 1, 2, 3, 4, 6, 9, 12 h postgavage. For Trial 2, 24 pigs were randomly allocated to one terminal collection time point at 0, 2, 4, 6, 8 or 10 h postgavage. Synovial fluid was analyzed to determine TVN and 3AT concentrations. TVN and 3AT were detected in Trial 1 at all time points, except 0 h. At 2 h postgavage for trial 2, the mean concentrations peaked at 31.17 ng/mL (95% CI: 18.62-52.16) for TVN and at 58.82 ng/mL (95% CI: 35.14-98.46) for 3AT. Storage duration did not impact TVN or 3AT concentrations (P-value 0.9732). © 2016 John Wiley & Sons Ltd.

Allogeneic human dermal fibroblasts are viable in peripheral blood mononuclear co-culture

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Restu Syamsul Hadi

2014-08-01

Full Text Available Background Transplanted allogeneic dermal fibroblasts retain stem cell subpopulations, and are easily isolated, expanded and stored using standard techniques. Their potential for regenerative therapy of chronic wounds should be evaluated. The aim of this study was to determine allogeneic fibroblast viability in the presence of peripheral blood mononuclear cells (PBMC. Methods In this experimental study, fibroblasts were isolated from foreskin explants, expanded in the presence of serum, and stored using slow-freezing. We used one intervention group of allogeneic fibroblasts co-cultured with PBMC and 2 control groups of separate fibroblast and PBMC cultures.Fibroblasts were characterized by their collagen secretion and octamer-binding transcription factor 4 (OCT4 expression. Viability was evaluated using water soluble tetrazolium-1 (WST-1 proliferation assay. Absorbances were measured at 450 nm. Data analysis was performed by student’s paired t-test. Results Dermal fibroblasts were shown to secrete collagen, express OCT4, be recoverable after cryopreservation, and become attached to the culture dish in a co-culture with PBMC. Co-cultured and control fibroblasts had no significantly different cell viabilities (p>0.05. Calculated viable cell numbers increased 1.8 and 5.1-fold, respectively, at days 2 and 4 in vitro. Both groups showed comparable doubling times at days 2 and 4 in vitro. PBMC did not interfere with allogeneic fibroblast viability and proliferative capacity Conclusions Allogeneic fibroblasts remain viable and proliferate in the presence of host PBMC. Future research should evaluate allogeneic human dermal fibroblast competency in clinical settings. Dermal fibroblasts are a potential source for cell therapy in chronic wound management.

Synovial hemangioma in an adult horse.

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Holzhausen, Lars; Nowak, Michael; Junginger, Johannes; Puff, Christina

2012-03-01

A 15-year-old gelding presented with a progressive lameness of the left forelimb of 2.5 months duration. Clinically, a dilation of the deep flexor tendon sheath with a firm elastic consistency and a pronounced tenderness was noted. Ultrasonically, a marked swelling of the flexor tendon sheath with an irregular density of the mesotendineum was observed. The white, firm material forming a nodular distension of the flexor tendon sheath with a diameter of approximately 1 cm was excised and sent for histopathological examination. Biopsies of the deep flexor tendon and corresponding tendon sheath were sent for histopathological evaluation. Histologically, the mass consisted of clefts and numerous anastomosing vascular channels extending between the collagen fibers of the deep flexor tendon. These capillary-like spaces were lined by neoplastic cells that were flattened to polygonal and contained few erythrocytes. There was 0 to 1 mitotic figure per 10 high power fields (400×). Immunohistochemically, the neoplastic cells stained positive for vimentin and factor VIII-related antigen. Adjacent to the neoplastic endothelial cells located pericytes expressed α-smooth muscle actin antigen. Based on the histopathological and immunohistochemical features, synovial hemangioma was diagnosed. One year after surgery, the horse has shown no lameness.

Ets2 in tumor fibroblasts promotes angiogenesis in breast cancer.

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Julie A Wallace

Full Text Available Tumor fibroblasts are active partners in tumor progression, but the genes and pathways that mediate this collaboration are ill-defined. Previous work demonstrates that Ets2 function in stromal cells significantly contributes to breast tumor progression. Conditional mouse models were used to study the function of Ets2 in both mammary stromal fibroblasts and epithelial cells. Conditional inactivation of Ets2 in stromal fibroblasts in PyMT and ErbB2 driven tumors significantly reduced tumor growth, however deletion of Ets2 in epithelial cells in the PyMT model had no significant effect. Analysis of gene expression in fibroblasts revealed a tumor- and Ets2-dependent gene signature that was enriched in genes important for ECM remodeling, cell migration, and angiogenesis in both PyMT and ErbB2 driven-tumors. Consistent with these results, PyMT and ErbB2 tumors lacking Ets2 in fibroblasts had fewer functional blood vessels, and Ets2 in fibroblasts elicited changes in gene expression in tumor endothelial cells consistent with this phenotype. An in vivo angiogenesis assay revealed the ability of Ets2 in fibroblasts to promote blood vessel formation in the absence of tumor cells. Importantly, the Ets2-dependent gene expression signatures from both mouse models were able to distinguish human breast tumor stroma from normal stroma, and correlated with patient outcomes in two whole tumor breast cancer data sets. The data reveals a key function for Ets2 in tumor fibroblasts in signaling to endothelial cells to promote tumor angiogenesis. The results highlight the collaborative networks that orchestrate communication between stromal cells and tumor cells, and suggest that targeting tumor fibroblasts may be an effective strategy for developing novel anti-angiogenic therapies.

Synovial chondromatosis simulating neoplastic degeneration of osteochondroma: findings on MRI and CT

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Schofield, T.D.; Pitcher, J.D.; Youngberg, R.

1994-01-01

A case is presented of synovial chondromatosis within a bursal sac overlying an osteochondroma in a patient with osteochondromatosis. This condition presented with a symptomatic soft tissue mass containing calcified bodies. It can be mistaken clinically and radiographically for malignant degeneration of an osteocondroma with development of chondrosarcoma. Mangetic resonance findings have not previously been described in this entity and proved helpful in the preoperative diagnosis. Magnetic resonance imaging was also helpful in defining the extent of the lesion. Ultrasound and other imaging modalities are also discussed, including the pathologic basis for the radiographic findings. (orig.)

PKCδ inhibition normalizes the wound-healing capacity of diabetic human fibroblasts.

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Khamaisi, Mogher; Katagiri, Sayaka; Keenan, Hillary; Park, Kyoungmin; Maeda, Yasutaka; Li, Qian; Qi, Weier; Thomou, Thomas; Eschuk, Danielle; Tellechea, Ana; Veves, Aris; Huang, Chenyu; Orgill, Dennis Paul; Wagers, Amy; King, George L

2016-03-01

Abnormal fibroblast function underlies poor wound healing in patients with diabetes; however, the mechanisms that impair wound healing are poorly defined. Here, we evaluated fibroblasts from individuals who had type 1 diabetes (T1D) for 50 years or more (Medalists, n = 26) and from age-matched controls (n = 7). Compared with those from controls, Medalist fibroblasts demonstrated a reduced migration response to insulin, lower VEGF expression, and less phosphorylated AKT (p-AKT), but not p-ERK, activation. Medalist fibroblasts were also functionally less effective at wound closure in nude mice. Activation of the δ isoform of protein kinase C (PKCδ) was increased in postmortem fibroblasts from Medalists, fibroblasts from living T1D subjects, biopsies of active wounds of living T1D subjects, and granulation tissues from mice with streptozotocin-induced diabetes. Diabetes-induced PKCD mRNA expression was related to a 2-fold increase in the mRNA half-life. Pharmacologic inhibition and siRNA-mediated knockdown of PKCδ or expression of a dominant-negative isoform restored insulin signaling of p-AKT and VEGF expression in vitro and improved wound healing in vivo. Additionally, increasing PKCδ expression in control fibroblasts produced the same abnormalities as those seen in Medalist fibroblasts. Our results indicate that persistent PKCδ elevation in fibroblasts from diabetic patients inhibits insulin signaling and function to impair wound healing and suggest PKCδ inhibition as a potential therapy to improve wound healing in diabetic patients.

Biochemical mechanisms of skin radiation burns inhibition and healing by the volumetric autotransplantation of fibroblasts and of keratinocytes with fibroblasts composition

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L. V. Altukhova

2015-09-01

Full Text Available Mechanisms of influence of volumetric autotransplantation of fibroblasts and of the mixture of fibroblasts and keratinocytes on the development of the local 3rd degree X-ray burn and the radiation skin ulcer in guinea pigs were investigated. We used deepadministration into the irradiation zone on its perimeter of 6 doses, which contained (150–160×103 fibroblasts and (130–140×103 keratinocytes in 100 µl. It is shown that this autotransplantation carried out 1 hour after the irradiation, and then every 24 hours, reduces the area of burn on the 35th day, compared to the control by 63%. Radiation ulcer appears on the 10th day after irradiation and is completely healed on the 25th day. With the same regimen of administration of only fibroblasts containing (200–210×103 cells in 100 µl, these parameters of treatment were equal to 31% on 4th and 35th day, respectively. It is shown that as a result of radiation in the area of burn the level of gene expression of collagen types I and III, elastin, fibronectin, vinculin, decorin, hyaluronansynthases 1, 2, 3, matrix metalloproteinases 1, 2, 3, 7, 9 and hyaluronidase is reduced. Besides, in the burn area the level of gene expression of transforming growth factor α, fibroblast growth factors 1, 2, 8 and anti-inflammatory cytokines – interleukin 10 and transforming growth factor-β1 – is reduced, while the level of gene expression of proinflammatory cytokine (interleykin1β increases. Both types of autotransplantation cause the growth of the expression level of all the structural genes and regulatory proteins of biopolymers and decrease in the expression level of interleukin 1β, which leads to activation of tissue regeneration and healing of the burn wound. Reasonsfor the higher efficiency of autotransplantation using the mixture of fibroblasts and keratinocytes compared to autotransplantation by fibroblasts only are both the larger total number of live cells regularly replacing dead cells in

Protective effects of methanolic extract of Adhatoda vasica Nees leaf in collagen-induced arthritis by modulation of synovial toll-like receptor-2 expression and release of pro-inflammatory mediators

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Rana Adhikary

2016-03-01

Full Text Available RA associated with oxidative stress and chronic inflammation has been a major health problem among the population worldwide. In this study protective effect of methanolic extract of Adhatoda vasica leaf (AVE was evaluated on Collagen-induced arthritis in male Swiss albino mice. Post oral administration of AVE at 50, 100 and 200 mg/kg body weight doses decreased the arthritic index and footpad swelling. AVE administration diminished pro-inflammatory cytokines in serum and synovial tissues. Reduced chemokines and neutrophil infiltration in synovial tissues after AVE administration dictated its protective effect against RA. Decreased LPO content and SOD activity along with concomitant rise in GSH and CAT activities from liver, spleen and synovial tissues indicated regulation of oxidative stress by AVE. In addition decreased CRP in serum along with suppressed TLR-2 expression in CIA mice after AVE treatment was also observed. Protective effect of AVE in RA is further supported from histopathological studies which showed improvement during bone damage. In conclusion this study demonstrated A. vasica is capable of regulating oxidative stress during CIA and therefore down regulated local and systemic release of pro-inflammatory mediators, which might be linked to mechanism of decreasing synovial TLR-2 expression via downregulating release of its regular endogenous ligands like CRP.

Evaluation of Partial Transection versus Synovial Debridement of the ACL as Novel Canine Models for Management of ACL Injuries.

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Bozynski, Chantelle C; Kuroki, Keiichi; Stannard, James P; Smith, Patrick A; Stoker, Aaron M; Cook, Cristi R; Cook, James L

2015-10-01

A major hurdle in investigating important clinical questions in knee ligament treatment is a lack of valid translational animal models. This study characterizes the effects of partial transection versus synovial debridement of the anterior (cranial) cruciate ligament (ACL) in dogs. A total of 27 adult purpose-bred research hounds underwent surgery and were assessed over the following 8 weeks. Dogs were randomized into the following three ACL status groups: sham control (n = 9), intact ACL with synovial debridement (exposed ACL) (n = 9), and partial transection of the ACL (partial tear ACL) (n = 9). Dogs in the exposed ACL group and partial tear ACL group had significantly (p < 0.05) more severe lameness, pain, effusion, reduced function, and reduced comfortable range of motion compared with controls, with the partial tear ACL group being most severely affected. More severe ACL and whole-joint pathology, and radiographic scores for osteoarthritis were present in the partial tear ACL group compared with exposed and/or sham control group. On the basis of these findings, biologic components of ACL injury (exposed ACL) played a role in whole-joint inflammation, but the clinical and pathological effects were more severe when both biologic and biomechanical components were present (i.e., partial tear ACL). These novel canine models were successfully developed to evaluate partial transection versus synovial debridement of the ACL and these models will be used to evaluate treatment options for acute management of ACL injuries. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Cell proliferation in vitro modulates fibroblast collagenase activity