Development of an ex vivo cellular model of rheumatoid arthritis: Critical role of cd14‐positive monocyte/macrophages in the development of pannus tissue

Nozaki, Toshiko; Takahashi, Kyôko; Ishii, Osamu; Endo, Sachio; Hioki, Kyoji; Mori, Taisuke; Kikukawa, Tadahiro; Boumpas, Dimitrios T.; Ozaki, Shoichi; Yamada, Hisakata

doi:10.1002/art.22849

Cited by 14 publications

(30 citation statements)

References 41 publications

(41 reference statements)

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“…Although animal models can yield an overall understanding of RA pathogenesis, these models also have serious limitations. Due to discrepancies between human arthritis and animal models of arthritis, some responses are different [20]. Importantly, although many drugs have shown great potency in animal models, this advantage has not been borne out in clinical trials [20, 36].…”

Section: Discussionmentioning

confidence: 99%

“…Due to discrepancies between human arthritis and animal models of arthritis, some responses are different [20]. Importantly, although many drugs have shown great potency in animal models, this advantage has not been borne out in clinical trials [20, 36]. Relatedly, the key point of RA progression is associated with the inflammation of the synovial membrane around the RA joint [3].…”

Section: Discussionmentioning

confidence: 99%

“…Relatedly, the key point of RA progression is associated with the inflammation of the synovial membrane around the RA joint [3]. Thus, in vitro models that use human cells were developed to study the mechanism of RA and possible therapeutic approaches [20]. Therefore, primary human fibroblast-like synoviocytes from RA patients have been used to screen and study the unique effects of many drugs and phytochemicals [21–23].…”

Section: Discussionmentioning

confidence: 99%

“…The use of human cells was established to study the mechanism of RA and possible therapeutic approaches [20]. Thus, primary human fibroblast-like synoviocytes isolated from RA patients have been used to study the effects of a variety of drugs and phytochemicals [21–23].…”

Section: Introductionmentioning

confidence: 99%

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Effects of sesamin on primary human synovial fibroblasts and SW982 cell line induced by tumor necrosis factor-alpha as a synovitis-like model

Khansai

Phitak

Klangjorhor

et al. 2017

BMC Complement Altern Med

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BackgroundRheumatoid arthritis (RA) is an autoimmune disease that causes chronic synovitis, cartilage degradation and bone deformities. Synovitis is the term for inflammation of the synovial membrane, an early stage of RA. The pathogenesis of the disease occurs through cytokine induction. The major cytokine that increases the severity of RA is TNF-α. Thus, inhibition of the TNF-α cascade is an effective way to diminish the progression of the disease. We are interested in investigating the difference between primary human synovial fibroblast (hSF) cells and SW982 as synovitis models induced by TNF-α and in monitoring their responses to sesamin as an anti-inflammatory phytochemical.MethodThe designed experiments were performed in hSF cells or the SW982 cell line treated with 10 ng/ml TNF-α with or without 0.25, 0.5 or 1 μM sesamin. Subsequently, pro-inflammatory cytokine genes and proteins were measured in parallel with a study of associated signalling transduction involved in inflammatory processes, including NF-κB and MAPK pathways.ResultsThe results demonstrated that although hSF and SW982 cells responded to TNF-α induction in the same fashion, they reacted at different levels. TNF-α could induce IL-6, IL-8 and IL-1β in both cell types, but the levels in SW982 cells were much higher than in hSF cells. This characteristic was due to the different induction of MAPKs in each cell type. Both cell types reacted to sesamin in almost the same fashion. However, hSF cells were more sensitive to sesamin than SW982 cells in terms of the anti-RA effect.ConclusionsThe responses of TNF-α-induced hSF and SW982 were different at the signal transduction level. However, the two cell types showed almost the same reaction to sesamin treatment in terms of the end point of the response.Electronic supplementary materialThe online version of this article (10.1186/s12906-017-2035-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effects of sesamin on primary human synovial fibroblasts and SW982 cell line induced by tumor necrosis factor-alpha as a synovitis-like model

Khansai

Phitak

Klangjorhor

et al. 2017

BMC Complement Altern Med

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“…12 It has been previously shown that targeted depletion of synovial macrophages by using anti-CD14-conjugated magnetic beads in RA synovial cells improves inflammation. 13,14 For OA, it has also been shown that OA synovial macrophages likely play an important role in activating the fibroblasts and perpetuating the production of proinflammatory cytokines and destructive enzymes. Although the levels of proinflammatory cytokines are generally lower in OA than those are in RA, IL-1b and TNF-a have been suggested as the key players in OA synovial inflammation.…”

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confidence: 99%

Effects of CD14 Macrophages and Proinflammatory Cytokines on Chondrogenesis in Osteoarthritic Synovium-Derived Stem Cells

Sun

Lee

Seong

et al. 2014

Tissue Engineering Part A

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We investigated the effects of CD14 macrophages and proinflammatory cytokines on chondrogenic differentiation of osteoarthritic synovium-derived stem cells (SDSCs). Osteoarthritic synovial fluid was analyzed for interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), and IL-6. Levels of stem cell surface markers in osteoarthritic SDSCs were evaluated using flow cytometry. CD14-negative cells were obtained using magnetically activated cell sorting. We compared chondrogenic potentials between whole cells and CD14-negative cells in CD14 low cells and CD14 high cells, respectively. To assess whether nuclear factor-kB (NF-kB) and CCAAT/enhancer-binding protein b (C/EBPb) modulate IL-1b-induced alterations in chondrogenic potential, we performed small interfering RNA transfection. We observed a significant correlation between the CD14 ratio in osteoarthritic SDSCs and IL-1b and TNF-a in osteoarthritic synovial fluid. Phenotypic characterization of whole cells and CD14-negative cells showed no significant differences in levels of stem cell markers. mRNA expression of type II collagen was higher in CD14-negative cell pellets than in whole cell pellets. Immunohistochemical staining indicated higher levels of type II collagen in the CD14-negative cell pellets of CD14 high cells than in whole cell pellets of CD14 high cells. As expected, IL-1b and TNF-a significantly inhibited the expression of chondrogenic-related genes in SDSCs, an effect which was antagonized by knockdown of NF-kB and C/EBPb. Our results suggest that depletion of CD14 + synovial macrophages leads to improved chondrogenic potential in CD14 high cell populations in osteoarthritic SDSCs, and that NF-kB (RelA) and C/EBPb are critical factors mediating IL-1b-induced suppression of the chondrogenic potential of human SDSCs.

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Endogenous prostaglandin E₂ inhibits aberrant overgrowth of rheumatoid synovial tissue and the development of osteoclast activity through EP4 receptor

Shibata-Nozaki

Mitomi

et al. 2011

Arthritis & Rheumatism

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Objective. We recently developed an ex vivo cellular model of pannus, the aberrant overgrowth of human synovial tissue. This study was undertaken to use that model to investigate the role of prostaglandin E 2 (PGE 2 ) and its receptor subtypes in the development of pannus growth and osteoclast activity in rheumatoid arthritis (RA).Methods. Inflammatory cells that infiltrated pannus from patients with RA were collected without enzyme digestion and designated synovial tissue-derived inflammatory cells. Their single-cell suspensions were cultured in medium alone to observe an aberrant overgrowth of inflammatory tissue in vitro. Levels of cytokines produced in culture supernatants were measured using enzyme-linked immunosorbent assay kits. Osteoclast activity was assessed by the development of resorption pits in calcium phosphate-coated slides.Results. Primary culture of the synovial tissuederived inflammatory cells resulted in spontaneous reconstruction of inflammatory tissue in vitro within 4 weeks, during which tumor necrosis factor ␣, PGE 2 , macrophage colony-stimulating factor, and matrix metalloproteinase 9 were produced in the supernatant. This aberrant overgrowth was inhibited by antirheumatic drugs including methotrexate and infliximab. On calcium phosphate-coated slides, synovial tissue-derived inflammatory cells showed numerous resorption pits. In the presence of inhibitors of endogenous prostanoid production such as indomethacin and NS398, exogenous PGE 1 and EP4-specific agonists significantly inhibited all these activities of synovial tissue-derived inflammatory cells in a dose-dependent manner. Addition of indomethacin, NS398, or EP4-specific antagonist resulted in the enhancement of these cells' activities. EP2-specific agonist had a partial effect, while EP1-and EP3-specific agonists had no significant effects.Conclusion. These results suggest that endogenous PGE 2 produced in rheumatoid synovium negatively regulates aberrant synovial overgrowth and the development of osteoclast activity via EP4.Rheumatoid arthritis (RA) is a progressive, systemic inflammatory disorder that is characterized by a chronic synovitis which leads to pannus formation and joint destruction. Pannus tissue is composed mainly of activated macrophages, T cells, and proliferating fibroblast-like synoviocytes (FLS) (1-3). Both cytokine networks and cell-cell interaction contribute to the development of pannus tissue. Previous studies indicated that both peripheral blood and synovial monocyte/ macrophages had the ability to serve as osteoclast precursors and developed osteoclastic activity when cocultured with either CD14Ϫ synovial cells or FLS in the presence of macrophage colony-stimulating factor (M-CSF) (4). Cultured synovial fibroblasts and mesen-

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Development of an ex vivo cellular model of rheumatoid arthritis: Critical role of cd14‐positive monocyte/macrophages in the development of pannus tissue

Cited by 14 publications

References 41 publications

Effects of sesamin on primary human synovial fibroblasts and SW982 cell line induced by tumor necrosis factor-alpha as a synovitis-like model

Effects of sesamin on primary human synovial fibroblasts and SW982 cell line induced by tumor necrosis factor-alpha as a synovitis-like model

Effects of CD14 Macrophages and Proinflammatory Cytokines on Chondrogenesis in Osteoarthritic Synovium-Derived Stem Cells

Endogenous prostaglandin E₂ inhibits aberrant overgrowth of rheumatoid synovial tissue and the development of osteoclast activity through EP4 receptor

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Development of an ex vivo cellular model of rheumatoid arthritis: Critical role of cd14‐positive monocyte/macrophages in the development of pannus tissue

Cited by 14 publications

References 41 publications

Effects of sesamin on primary human synovial fibroblasts and SW982 cell line induced by tumor necrosis factor-alpha as a synovitis-like model

Effects of sesamin on primary human synovial fibroblasts and SW982 cell line induced by tumor necrosis factor-alpha as a synovitis-like model

Effects of CD14 Macrophages and Proinflammatory Cytokines on Chondrogenesis in Osteoarthritic Synovium-Derived Stem Cells

Endogenous prostaglandin E2 inhibits aberrant overgrowth of rheumatoid synovial tissue and the development of osteoclast activity through EP4 receptor

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Endogenous prostaglandin E₂ inhibits aberrant overgrowth of rheumatoid synovial tissue and the development of osteoclast activity through EP4 receptor