The synovial lining micromass system: Toward rheumatoid arthritis in a dish?

Perlman, Harris; Pope, Richard M.

doi:10.1002/art.27297

Cited by 17 publications

(13 citation statements)

References 17 publications

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“…A characteristic feature of RA is the hyperplasia of the synovial tissue, resulting from the infiltration of various types of immune cells secreting numerous cytokines, chemokines, and matrix metalloproteinases (MMPs) that promote inflammation and joint destruction through autocrine and paracrine mechanisms [26]. In particular, synovial fibroblasts and macrophages have been identified as the major cell population in the synovial tissue for overproduction of both proinflammatory cytokines and MMPs.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis

Wang

Feng

et al. 2012

Arthritis Res Ther

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IntroductionThe immunoregulatory function of interleukin (IL)-29 has recently been recognized. However, little is known about the involvement of IL-29 in the pathogenesis of rheumatoid arthritis (RA). This study aimed to examine the expression profiles of IL-29 in blood, synovial fluid (SF) and synovium in RA patients and investigate the effect of IL-29 on cytokines production in RA synovial fibroblasts.MethodsThe transcript levels of IL-29 and its specific receptor IL-28Rα in peripheral blood mononuclear cells (PBMC) and synovium were determined by real-time reverse transcription-polymerase chain reaction (real-time PCR). The concentrations of IL-29 in serum and synovial fluid (SF) were quantified by enzyme-linked immunoassay (ELISA), and the correlation of serum IL-29 levels with disease activity in RA patients was investigated. Furthermore, the expression of IL-29 in RA synovium was examined by immunohistochemistry and double immunofluorescence analysis. Finally, the expression of IL-6, IL-8, IL-10, IL-17 and matrix metalloproteinase-3 (MMP-3) in synovial fibroblasts upon IL-29 stimulation was determined by real-time PCR.ResultsIL-29 and IL-28Rα mRNA expression in PBMC was significantly increased in patients with RA compared with healthy controls (HC). The serum levels of circulating IL-29 were higher in RA than those in HC. Increased IL-29 levels were detected in RA SF when compared with osteoarthritis (OA) SF. However, serum IL-29 levels showed no significant correlation with RA disease activity. IL-29 was mostly expressed in the lining region of RA synovium. Moreover, IL-29 was expressed predominately in synovial macrophages and fibroblasts. RA synovial fibroblasts exposed to IL-29 specifically upregulated IL-6, -8 and MMP-3 but downregulated IL-10.ConclusionsThe findings in the present study indicate, for the first time, that IL-29 is dysregulated in patients with RA, which may contribute to the RA pathogenesis via inducing the production of proinflammatory cytokines, chemokines or matrix metalloproteinases in synovial fibroblasts.

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Section: Discussionmentioning

confidence: 99%

Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis

Wang

Feng

et al. 2012

Arthritis Res Ther

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“…SFs also produce matrix components, such as collagen and a series of matrix-degrading enzymes, to participate in the continuous matrix remodeling ( 5 , 6 ). However, in RA, the synovial lining thickness increases to 10–15 cell layers ( 7 , 8 ), and the SFs are activated to become RASFs, which damage the cartilage by producing inflammatory cell factors and causing matrix degradation ( 9 ). Therefore, an improved understanding of the characteristics of SFs will be important for identifying the contribution of this specific cell type to the pathogenesis of RA.…”

Section: Introductionmentioning

confidence: 99%

A protocol for the culture and isolation of murine synovial fibroblasts

Zhao

Ouyang

et al. 2016

Biomedical Reports

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The culture of synovial fibroblasts (SFs) is one of the most effective tools for investigating the pathology and physiology of synovial tissues and should prove useful for identifying the importance of SFs in disease as well as for the development of novel therapeutic approaches for several chronic joint diseases, such as rheumatoid arthritis. However, thus far, a detailed protocol for the primary culture and isolation of murine SFs has not been established. Therefore, the present study describes an easy and convenient method for isolating and culturing SFs from C57BL/6 mice. This protocol can be divided into 4 stages: Isolation of synovial tissues, isolation of SFs, seeding of SFs for growth in culture and purity analysis of SFs using the four cell markers, vimentin, cluster of differentiation 90.2 (CD90.2; Thy-1.2), intracellular adhesion molecule 1 (CD54) and vascular cell adhesion molecule 1 (CD106). This method is efficient and a purified population of SFs can be obtained 10 days after the initiation of culture.

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“…One explanation of the limited HA synthesis from K4IM cells might be related to the culture system in monolayer. Synoviocytes grown in three‐dimensional organ culture reveal a lining organization at the interface between matrix and fluid phase that is more similar to the one seen in vivo compared with the monolayer culture (Kiener, Lee, Agarwal, & Brenner, ; D. M. Lee et al, ; Perlman & Pope, ). Viscosupplementation via intraarticular injections of HA products is used as a conservative treatment in OA patients (Jüni et al, ).…”

Section: Resultsmentioning

confidence: 94%

Cultures of a human synovial cell line to evaluate platelet-rich plasma and hyaluronic acid effects

Olivotto

Merli

Assirelli

et al. 2018

J Tissue Eng Regen Med

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Synovial inflammation plays an important role in osteoarthritis (OA) pathogenesis. Different biological compounds have been tested mainly on chondrocytes, to treat early stages of OA. However, because OA has been recently defined as "an organ" pathology, investigation on synoviocytes is also needed. Therefore, the aim of the present study was to validate a human fibroblast-like synoviocytes cell line (K4IM) to test the effects of platelet-rich plasma (PRP) and hyaluronan (HA) on anabolic and catabolic gene expression and on HA secretion from cell cultures. In order to determine the effect of PRP and HA, K4IM cells were maintained in culture with or without TNF-α stimulation. In the presence of PRP, unstimulated K4IM cells presented the same expression of IL1B, IL6, CXCL8, VEGF, TIMP1, and hyaluronic synthase isoform HAS3 as primary human synoviocytes, while HA addition did not change their expression pattern, which was similar to control cells. Stimulated cells expressed significantly higher values of IL1B, CXCL8, and VEGF compared with unstimulated ones. PRP did not show any modification, except for VEGF, while HA addition modulated IL1B expression. PRP did not modulate HA release of both stimulated and unstimulated cells. Our study showed the possibility to use K4IM synoviocytes as an in vitro model to test biological compounds useful for the treatment of early OA. Primary cells reflect the phenotype of cells in vivo, but limited recovery from biopsies and restricted lifespan makes experimental manipulation challenging. Therefore, despite cell lines present some limitations, they could be used as an alternative for preliminary experiments.

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The synovial lining micromass system: Toward rheumatoid arthritis in a dish?

Cited by 17 publications

References 17 publications

Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis

Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis

A protocol for the culture and isolation of murine synovial fibroblasts

Cultures of a human synovial cell line to evaluate platelet-rich plasma and hyaluronic acid effects

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