Migratory potential of rheumatoid arthritis synovial fibroblasts: Additional perspectives

Neumann, Elena; Lefèvre, Stephanie; Zimmermann, Birgit; Geyer, Matthias; Lehr, A.; Umscheid, Thomas; Schönburg, Markus; Rehart, Stefan; Müller‐Ladner, Ulf

doi:10.4161/cc.9.12.11907

Cited by 23 publications

(34 citation statements)

References 56 publications

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“…RASF adhesion to extracellular matrix or cells is essential for RASF migration and cartilage invasion (24,25). RASF adhesion to cartilage was significantly reduced by RNase (cells/visual field, 11.9 6 2.9 versus 34.5 6 4.2 for control, p = 0.001) (Fig.…”

Section: Modulation Of Rasf Adhesion and Proliferation By Exrnamentioning

confidence: 90%

“…Synovium was snap frozen or used for SF isolation. SF culture was performed as described previously (24,25,31) in DMEM containing 100 U/ml penicillin/streptomycin, 12.5 mM HEPES (all PAA Laboratories, Cölbe, Germany), and 10% FCS (Sigma-Aldrich, Taufkirchen, Germany) with 10% CO 2 at 37˚C. Dermal fibroblasts from RA patients (RADF) or healthy volunteers (normal dermal fibroblasts [NDF]) were isolated and cultured according to RASF; normal synovial fibroblasts (NSF) were from Cell Applications (San Diego, CA).…”

Section: Methodsmentioning

confidence: 99%

“…According to established protocols (24), Crl-scidBR mice (Charles River Laboratories) underwent implantation surgery. In brief, ipsilaterally, a gelatin matrix containing human cartilage with 1.5 3 10 5 RASF (34) and, contralaterally, cartilage in a gelatin matrix without RASF were s.c. implanted (24,25). Animals received i.v.…”

Section: Rnase1 Treatment In the Scid Mouse Model Of Ramentioning

confidence: 99%

“…Following termination of the experiment after 45 d, implants were removed and snap frozen. Cartilage invasion by RASF was scored (five blinded researchers) (24,25,34).…”

Section: Rnase1 Treatment In the Scid Mouse Model Of Ramentioning

confidence: 99%

“…RASF are activated cells with increased production of proinflammatory factors, matrix-degrading enzymes, enhanced matrix adhesion, and cell migration (23). RASF are able to leave their local environment and migrate to distant cartilage (24,25). The proinflammatory role of extracellular nucleic acids, specifically extracellular mitochondrial DNA and oxidized DNA, has been previously demonstrated in an arthritis model (26).…”

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confidence: 99%

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Influence of Extracellular RNAs, Released by Rheumatoid Arthritis Synovial Fibroblasts, on Their Adhesive and Invasive Properties

Zimmermann-Geller

Köppert

Fischer

et al. 2016

The Journal of Immunology

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Extracellular RNA (exRNA) has been characterized as a molecular alarm signal upon cellular stress or tissue injury and to exert biological functions as a proinflammatory, prothrombotic, and vessel permeability–regulating factor. In this study, we investigated the contribution of exRNA and its antagonist RNase1 in a chronic inflammatory joint disease, rheumatoid arthritis (RA). Upon immunohistochemical inspection of RA, osteoarthritis (OA), and psoriatic arthritis synovium, exRNA was detectable only in the RA synovial lining layer, whereas extracellular DNA was detectable in various areas of synovial tissue. In vitro, exRNA (150–5000 nt) was released by RA synovial fibroblasts (RASF) under hypoxic conditions but not under normoxia or TNF-α treatment. RNase activity was increased in synovial fluid from RA and OA patients compared with psoriatic arthritis patients, whereas RNase activity of RASF and OASF cultures was not altered by hypoxia. Reduction of exRNA by RNase1 treatment decreased adhesion of RASF to cartilage, but it had no influence on their cell proliferation or adhesion to endothelial cells. In vivo, treatment with RNase1 reduced RASF invasion into coimplanted cartilage in the SCID mouse model of RA. We also analyzed the expression of neuropilins in synovial tissue and SF, as they may interact with vascular endothelial growth factor signaling and exRNA. The data support the concepts that the exRNA/RNase1 system participates in RA pathophysiology and that RASF are influenced by exRNA in a prodestructive manner.

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Section: Modulation Of Rasf Adhesion and Proliferation By Exrnamentioning

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Rnase1 Treatment In the Scid Mouse Model Of Ramentioning

confidence: 99%

“…Following termination of the experiment after 45 d, implants were removed and snap frozen. Cartilage invasion by RASF was scored (five blinded researchers) (24,25,34).…”

Section: Rnase1 Treatment In the Scid Mouse Model Of Ramentioning

confidence: 99%

mentioning

confidence: 99%

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Influence of Extracellular RNAs, Released by Rheumatoid Arthritis Synovial Fibroblasts, on Their Adhesive and Invasive Properties

Zimmermann-Geller

Köppert

Fischer

et al. 2016

The Journal of Immunology

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Morin Acts as a USP7 Inhibitor to Hold Back the Migration of Rheumatoid Arthritis Fibroblast‐Like Synoviocytes in a “Prickle1‐mTORC2” Dependent Manner

Yang

Cao

Miao

et al. 2021

Molecular Nutrition Food Res

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Introduction The aim of this study is to investigate the effect and detailed mechanisms of morin, an anti‐arthritis compound widely distributed in foods of plant origin, on the pathological migration of fibroblast‐like synoviocytes (FLS). Methods and Results The migration of FLS collected from arthritis rats and MH7A cells is induced by platelet‐derived growth factor, and an arthritis model in rats is established by Freund's complete adjuvant. The results show that morin remarkably restrains FLS migration but slightly affects FLS apoptosis and proliferation. Moreover, in the progression of FLS migration, focal adhesion (FA) turnover is inhibited by morin via lowering the activation of Paxillin and focal adhesion kinase (FAK) and internalization of integrin β1. Morin disrupts the formation of mTOR complex 2 (mTORC2) and the activation of AKT (S473) and PKCα (S657), and MHY1485 reverses morin‐limited FLS migration. Of note, the protein stability of Prickle1, a binding factor of Rictor, is reduced by morin, and MG132 but not Baf A1 shows a repressive effect. Finally, the target protein is identified as ubiquitin‐specific protease 7 (USP7) but not USP9X. USP7 overexpressing plasmid weakens morin‐affected protein and ubiquitination of Prickle1, and mechanisms are confirmed in vivo by using an overexpressing plasmid and inhibitor. Conclusion Morin restricts FLS migration and arthritis by intervening in “USP7‐Prickle1‐mTORC2” signaling and FA turnover.

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Allgemeiner Aufbau und histologische Pathophysiologie der Tunica synovialis

Kriegsmann

Casadonte²,

Kriegsmann

2022

Arthroskopie

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Migratory potential of rheumatoid arthritis synovial fibroblasts: Additional perspectives

Cited by 23 publications

References 56 publications

Influence of Extracellular RNAs, Released by Rheumatoid Arthritis Synovial Fibroblasts, on Their Adhesive and Invasive Properties

Influence of Extracellular RNAs, Released by Rheumatoid Arthritis Synovial Fibroblasts, on Their Adhesive and Invasive Properties

Morin Acts as a USP7 Inhibitor to Hold Back the Migration of Rheumatoid Arthritis Fibroblast‐Like Synoviocytes in a “Prickle1‐mTORC2” Dependent Manner

Allgemeiner Aufbau und histologische Pathophysiologie der Tunica synovialis

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