title: Influence of Extracellular RNAs, Released by Rheumatoid Arthritis Synovial Fibroblasts, on Their Adhesive and Invasive Properties.
abstract: 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.
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus Liebig University Giessen, Kerckhoff Clinic, 61231 Bad Nauheim, Germany;
authors.forename: Birgit
authors.identifier: 0000-0003-1034-6657
authors.initials: B
authors.lastname: Zimmermann-Geller
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus Liebig University Giessen, Kerckhoff Clinic, 61231 Bad Nauheim, Germany;
authors.forename: Sina
authors.initials: S
authors.lastname: Köppert
authors.affiliation: Department of Biochemistry, Medical School, Justus Liebig University Giessen, 35392 Giessen, Germany;
authors.forename: Silvia
authors.initials: S
authors.lastname: Fischer
authors.affiliation: Department of Biochemistry, Medical School, Justus Liebig University Giessen, 35392 Giessen, Germany; Department of Microbiology, Kazan Federal University, Kazan 420008, Russian Federation;
authors.forename: Hector A
authors.identifier: 0000-0002-8502-7098
authors.initials: HA
authors.lastname: Cabrera-Fuentes
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus Liebig University Giessen, Kerckhoff Clinic, 61231 Bad Nauheim, Germany;
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lefèvre
authors.affiliation: Department of Orthopedics and Orthopedic Surgery, University Hospital Giessen and Marburg, 35392 Giessen, Germany;
authors.forename: Markus
authors.identifier: 0000-0001-6264-0888
authors.initials: M
authors.lastname: Rickert
authors.affiliation: Laboratory for Experimental Orthopedics, Department of Orthopedics and Orthopedic Surgery, University Hospital Giessen and Marburg, 35392 Giessen, Germany;
authors.forename: Jürgen
authors.initials: J
authors.lastname: Steinmeyer
authors.affiliation: Department of Orthopedics and Trauma Surgery, Markus Hospital, 60431 Frankfurt, Germany;
authors.forename: Stefan
authors.identifier: 0000-0003-2711-3550
authors.initials: S
authors.lastname: Rehart
authors.affiliation: Department of Vascular Surgery, HELIOS William Harvey Clinic, 61231 Bad Nauheim, Germany; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Umscheid
authors.affiliation: Department of Cardiac Surgery, Kerckhoff Clinic, 61231 Bad Nauheim, Germany.
authors.forename: Markus
authors.identifier: 0000-0002-7566-6769
authors.initials: M
authors.lastname: Schönburg
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus Liebig University Giessen, Kerckhoff Clinic, 61231 Bad Nauheim, Germany;
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.affiliation: Department of Biochemistry, Medical School, Justus Liebig University Giessen, 35392 Giessen, Germany; Department of Microbiology, Kazan Federal University, Kazan 420008, Russian Federation;
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Preissner
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus Liebig University Giessen, Kerckhoff Clinic, 61231 Bad Nauheim, Germany;
authors.forename: Klaus W
authors.initials: KW
authors.lastname: Frommer
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus Liebig University Giessen, Kerckhoff Clinic, 61231 Bad Nauheim, Germany; e.neumann@kerckhoff-klinik.de.
authors.forename: Elena
authors.initials: E
authors.lastname: Neumann
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D012313:RNA / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D013583:Synovial Membrane / Q000473:pathology*
chemical_list: D012313:RNA