Toll-like receptor 3 activation promotes joint degeneration in osteoarthritis
Osteoarthritis (OA) is characterized by cartilage degradation that is induced by inflammation. Sterile inflammation can be caused by damage-associated molecular patterns that are released by chondrocytes and activate pattern recognition receptors. We evaluate the role of toll-like receptor-3-activat...
Verfasser: | |
---|---|
FB/Einrichtung: | FB 13: Biologie |
Dokumenttypen: | Artikel |
Medientypen: | Text |
Erscheinungsdatum: | 2022 |
Publikation in MIAMI: | 05.09.2023 |
Datum der letzten Änderung: | 07.09.2023 |
Angaben zur Ausgabe: | [Electronic ed.] |
Quelle: | Cell Death and Disease 13 (2022), 224, 1-8 |
Schlagwörter: | Experimental models of disease; Trauma |
Fachgebiet (DDC): | 610: Medizin und Gesundheit |
Lizenz: | CC BY 4.0 |
Sprache: | English |
Förderung: | Finanziert über die DEAL-Vereinbarung mit Wiley 2019-2022. Förderer: Deutsche Forschungsgemeinschaft / Projektnummer: 272825466 |
Format: | PDF-Dokument |
URN: | urn:nbn:de:hbz:6-29928533300 |
Weitere Identifikatoren: | DOI: 10.17879/69928709840 |
Permalink: | https://nbn-resolving.de/urn:nbn:de:hbz:6-29928533300 |
Verwandte Dokumente: |
|
Onlinezugriff: | 10.1038_s41419-022-04680-5.pdf |
Osteoarthritis (OA) is characterized by cartilage degradation that is induced by inflammation. Sterile inflammation can be caused by damage-associated molecular patterns that are released by chondrocytes and activate pattern recognition receptors. We evaluate the role of toll-like receptor-3-activating RNA in the pathogenesis of OA. Toll-like receptor 3 (TLR3) was detected by semiquantitative reverse transcriptase PCR, western blotting and microscopy. Rhodamine-labelled poly(I:C) was used to image uptake in chondrocytes and full-thickness cartilage. The production of IFNβ in chondrocytes after stimulation with poly(I:C) as well as in the synovial fluid of OA patients was measured using ELISA. Chondrocyte apoptosis was chemically induced using staurosporine. Immunohistochemistry was performed to examine TLR3 expression and apoptosis in human and murine OA cartilage. RNA in synovial fluid was quantified by RiboGreen assay. Destabilisation of the medial meniscus was performed in TLR3−/− and wildtype mice. OA was assessed after eight weeks using OARSI score. TLR3 expression was confirmed by western blot and RT-PCR. Poly(I:C) was internalised by chondrocytes as well as cartilage and caused an increase of IFNβ production in murine (11.46 ± 11.63 (wo) to 108.7 ± 25.53 pg/ml; N = 6) and human chondrocytes (1.88 ± 0.32 (wo) to 737.6 ± 130.5 pg/ml; N = 3; p