Modulation of the response of rheumatoid arthritis synovial fibroblasts to proinflammatory stimulants with cyclic tensile strain

Bader, Rebecca A.; K, Wagoner

doi:10.1016/j.cyto.2010.03.015

Cited by 15 publications

(7 citation statements)

References 41 publications

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“…The present study showed that the IL‐1β protein in the culture supernatants was not detected at any point in time, although IL‐17 transiently increased the IL‐1β mRNA expression. It was reported that IL‐17 stimulated IL‐1β production in human monocytes/macrophages while IL‐1β was not detected following the stimulation with IL‐17 in synovial fibroblasts . Additionally, no report showed that IL‐17 had any effect on IL‐1β production in fibroblasts.…”

Section: Discussionmentioning

confidence: 98%

The effect of IL‐17 on the production of proinflammatory cytokines and matrix metalloproteinase‐1 by human periodontal ligament fibroblasts

Shibata

Shintaku

Matsuzaki

et al. 2014

Orthod Craniofacial Res

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Section: Discussionmentioning

confidence: 98%

The effect of IL‐17 on the production of proinflammatory cytokines and matrix metalloproteinase‐1 by human periodontal ligament fibroblasts

Shibata

Shintaku

Matsuzaki

et al. 2014

Orthod Craniofacial Res

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“…Previous studies have seen that the effect of cyclic strain on cytokine production, specifically in synovial cells, is dependent on the loading parameters. Short-term exposure (4h) to loads result in an increase in IL-6 and TNF-α [38], while long-term exposure (24h) at a slower strain rate also resulted in elevated IL-8 levels [67]. The variability in cytokine production from different loading parameters highlights the sensitivity of synoviocytes to different loading parameters.…”

Section: Discussionmentioning

confidence: 99%

Endogenous production of hyaluronan, PRG4, and cytokines is sensitive to cyclic loading in synoviocytes

Pendyala

Woods

Brubaker

et al. 2022

Preprint

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Synovial fluid is composed of hyaluronan and proteoglycan-4 (PRG4 or lubricin), which work synergistically to maintain joint lubrication. In diseases like osteoarthritis, hyaluronan and PRG4 concentrations can be altered, resulting in lowered synovial fluid viscosity, and pro-inflammatory cytokine concentrations within the synovial fluid increase. Synovial fibroblasts within the synovium are responsible for contributing to synovial fluid and can be targeted to improve endogenous production of hyaluronan and PRG4 and to alter the cytokine profile. We cyclically loaded SW982 synoviocytes to 0%, 5%, 10%, or 20% strain for three hours at 1 Hz. To assess the impact of substrate stiffness, we compared the 0% strain group to cells grown on tissue culture plastic. We measured the expression of hyaluronan turnover genes, hyaluronan localization within the cell layer, hyaluronan concentration, PRG4 concentration, and the cytokine profile within the media. Our results show that the addition of cyclic loading increased HAS3 expression, but not in a magnitude-dependent response. Hyaluronidase expression was impacted by strain magnitude, which is exemplified by the decrease in hyaluronan concentration due to cyclic loading. We also show that PRG4 concentration is increased at 5% strain, while higher strain magnitude decreases overall PRG4 concentration. Finally, 10% and 20% strain show a distinct, more pro-inflammatory cytokine profile when compared to the unloaded group. Multivariate analysis showed distinct separation between certain strain groups in being able to predict strain group, hyaluronan concentration, and PRG4 concentration from gene expression or cytokine concentration data, highlighting the complexity of the system. Overall, this study shows that cyclic loading can be used tool to modulate the endogenous production of hyaluronan, PRG4, and cytokines from synovial fibroblasts.

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“…Even with the lower proliferation rate, primary RASFs are more invasive of cartilage [17]. A recent study demonstrated that immortalized RASFs respond to mechanical stress diVerently compared with primary RASFs [18]. Additionally, immortalized cells have a higher level of p53 expression than primary RASFs [11].…”

Section: Introductionmentioning

confidence: 96%

Evaluation of SV40-transformed synovial fibroblasts in the study of rheumatoid arthritis pathogenesis

Bader

2011

Rheumatol Int

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The SV40 T antigen has been used to generate immortalized cells from rheumatoid arthritis (RA) synovial fibroblasts (RASFs) that are commonly used in lieu of primary RASFs. In the current study, we investigated the effect of stimulation by tissue necrosis factor alpha (TNF-α) and interleukin 17 (IL-17) on primary and immortalized RASFs in order to gauge the appropriateness of the use of immortalized RASFs, the MH7A cell line, in the study of RA pathogenesis. Changes in the levels of secretion and expression of 8 proteins associated with RA upon stimulation were assessed by multiplex immunoassay. IL-17 stimulation had a minimal impact on protein secretion and expression for primary and immortalized cells. Basic fibroblast growth factor (FGF-2) was not detectable for the primary cells but was detectable for the immortalized cells. In contrast, monocyte chemoattractant protein 1 (MCP-1) was detectable for primary cells but was undetectable for immortalized cells. In general, protein expression and secretion by cells stimulated with TNF-α were significantly increased. For primary cells, several proteins were below the limit of detection for unstimulated cells and cells stimulated with IL-17, while levels for TNF-α-stimulated cells were within the detectable range. For the same proteins, expression was observed for immortalized cells, regardless of stimulation, suggestive of constitutive activation of the NF-κB signaling pathway. The current study therefore provides strong evidence that immortalized and primary RASFs differ in regard to protein expression and secretion and therefore may not be appropriate for use in the study of RA pathogenesis.

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Modulation of the response of rheumatoid arthritis synovial fibroblasts to proinflammatory stimulants with cyclic tensile strain

Cited by 15 publications

References 41 publications

The effect of IL‐17 on the production of proinflammatory cytokines and matrix metalloproteinase‐1 by human periodontal ligament fibroblasts

The effect of IL‐17 on the production of proinflammatory cytokines and matrix metalloproteinase‐1 by human periodontal ligament fibroblasts

Endogenous production of hyaluronan, PRG4, and cytokines is sensitive to cyclic loading in synoviocytes

Evaluation of SV40-transformed synovial fibroblasts in the study of rheumatoid arthritis pathogenesis

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