Macrophage‐Derived Delta‐like Protein 1 Enhances Interleukin‐6 and Matrix Metalloproteinase 3 Production by Fibroblast‐like Synoviocytes in Mice With Collagen‐Induced Arthritis

Sekine, Chiyoko; Nanki, Toshihiro; Yagita, Hideo

doi:10.1002/art.38743

Cited by 13 publications

(3 citation statements)

References 25 publications

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“…Multiple cell types in the RA synovium produce Notch ligands including Delta1, Jagged1, and Jagged2. (4,36,37) These Notch ligands bind to Notch receptors expressed by synovial macs to activate Notch signaling. Notch activation is also involved in synovial T cell and B cell immune responses.…”

Section: Discussionmentioning

confidence: 99%

Targeting Notch-Activated M1 Macrophages Attenuates Joint Tissue Damage in a Mouse Model of Inflammatory Arthritis

Sun

Zhang

Wang

et al. 2017

Journal of Bone and Mineral Research

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Expression of Notch signaling molecules are increased in synovium from patients with rheumatoid arthritis (RA). However, it is not known which cell type(s) in RA synovium have Notch activation or if they play a pathogenetic role in RA. Here, we used Hes1-GFP/TNF-transgenic (TNF-Tg) mice to investigate the role of cells with active Notch signaling (GFP+) in RA. The number of GFP+ cells was significantly increased in synovium in Hes1-GFP/TNF-Tg mice and about 60% of them were F4/80+ macrophages expressing the inflammatory macrophage (M1) marker. TNF-Tg mice transplanted with Hes1-GFP/TNF-Tg bone marrow (BM) had significantly more GFP+ cells in their synovium than in BM. Intra-articular injection of Hes1-GFP/TNF-Tg or Hes1-GFP+ BM macrophages into WT and TNF-Tg mice showed highest synovial GFP+ cells in the TNF-Tg mice received Hes1-GFP/TNF-Tg cells. Thapsigargin, a Notch inhibitor, decreased TNF-induced M1 and increased M2 numbers and reduced joint lesion, synovial M1s and GFP+ cells in Hes1-GFP/TNF-Tg mice. Thapsigargin did not affect M1s from mice carrying a constitutively active Notch1. Thus, the main cells with activated Notch signaling in the inflamed synovium of TNF-Tg mice are M1s derived from BM and targeting which may represent a new therapeutic approach for patients with inflammatory arthritis.

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Section: Discussionmentioning

confidence: 99%

Targeting Notch-Activated M1 Macrophages Attenuates Joint Tissue Damage in a Mouse Model of Inflammatory Arthritis

Sun

Zhang

Wang

et al. 2017

Journal of Bone and Mineral Research

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“…Other Notch member-specific modulations have successfully attenuated experimental arthritis using HMD1-5 hamster anti-mouse Dll1 IgG (150,160) and anti-human and anti-mouse Notch3 IgG2a (151) mAbs. On the other side, anti-Jagged1 mAb-treated mice worsened CIA in one study (149), further corroborating the importance of specific targeting selective members of the Notch axis.…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Targeting the Notch Signaling Pathway in Chronic Inflammatory Diseases

et al. 2021

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The Notch signaling pathway regulates developmental cell-fate decisions and has recently also been linked to inflammatory diseases. Although therapies targeting Notch signaling in inflammation in theory are attractive, their design and implementation have proven difficult, at least partly due to the broad involvement of Notch signaling in regenerative and homeostatic processes. In this review, we summarize the supporting role of Notch signaling in various inflammation-driven diseases, and highlight efforts to intervene with this pathway by targeting Notch ligands and/or receptors with distinct therapeutic strategies, including antibody designs. We discuss this in light of lessons learned from Notch targeting in cancer treatment. Finally, we elaborate on the impact of individual Notch members in inflammation, which may lay the foundation for development of therapeutic strategies in chronic inflammatory diseases.

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“…Dexamethasone is commonly used to treat various inflammatory diseases and has moderate effect on OA and rheumatoid arthritis. However, long-term or high-dose dexamethasone should not be used since it may cause cell apoptosis and hormone-related side effects (Chung et al, 2011;Jia et al, 2011;Sekine et al, 2014;Shantha Kumara et al, 2014). Studies revealed that single high-dose dexamethasone could cause chondrocyte toxicity resulting in loss of cell viability and irreversible damage (Naves et al, 2011;Braun et al, 2012;Dragoo et al, 2012).…”

Section: +mentioning

confidence: 99%

Effect of Ginkgo biloba extract on matrix metalloproteinase-3 expression in a rat model of chondrocyte injury

Meng

et al. 2015

Genet. Mol. Res.

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ABSTRACT. A rat model with cartilage chondrocyte injury was established using interleukin-1β (IL-1β) to investigate the effect of Ginkgo biloba extract (EGb) on matrix metalloproteinase-3 (MMP-3) expression. Rat chondrocytes were extracted and randomly divided into six groups: control group, IL-1β (model) group, IL-1β + dexamethasone group, and IL-1β + EGb group (both high and low dose groups). Reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay were used to detect MMP-3 expression. Compared to the MMP-3 mRNA level in the control group, MMP-3 mRNA level significantly increased in the model group (P < 0.05). The application of dexamethasone or EGb significantly decreased the MMP-3 mRNA level (P < 0.05). MMP-3 mRNA and protein levels decreased in the EGb-treated group, especially in the high-dose group, compared to those in the dexamethasone group (P < 0.05). EGb EGb on IL-1β-induced chondrocyte damage may reduce MMP-3 production during IL-1β-induced chondrocyte damage and protect chondrocytes to some extent, with better efficacy at high doses.

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Macrophage‐Derived Delta‐like Protein 1 Enhances Interleukin‐6 and Matrix Metalloproteinase 3 Production by Fibroblast‐like Synoviocytes in Mice With Collagen‐Induced Arthritis

Cited by 13 publications

References 25 publications

Targeting Notch-Activated M1 Macrophages Attenuates Joint Tissue Damage in a Mouse Model of Inflammatory Arthritis

Targeting Notch-Activated M1 Macrophages Attenuates Joint Tissue Damage in a Mouse Model of Inflammatory Arthritis

Targeting the Notch Signaling Pathway in Chronic Inflammatory Diseases

Effect of Ginkgo biloba extract on matrix metalloproteinase-3 expression in a rat model of chondrocyte injury

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