PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Shen, P.* ; Serve, S.* ; Wu, P.* ; Liu, X.* ; Dai, Y.* ; Durán-Hernández, N.* ; Nguyen, D.T.M.* ; Fuchs, M.* ; Maleitzke, T.* ; Reisener, M.J.* ; Dzamukova, M.* ; Nussbaumer, K.* ; Brunner, T.M.* ; Li, Y.* ; Holecska, V.* ; Heinz, G.* ; Heinrich, F.* ; Durek, P.* ; Katsoula, G. ; Gwinner, C.* ; Jung, T.* ; Zeggini, E. ; Winkler, T.* ; Mashreghi, M.F.* ; Pumberger, M.* ; Perka, C.* ; Löhning, M.*

NOS inhibition reverses TLR2-induced chondrocyte dysfunction and attenuates age-related osteoarthritis.

Proc. Natl. Acad. Sci. U.S.A. 120:e2207993120 (2023)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Osteoarthritis (OA) is a joint disease featuring cartilage breakdown and chronic pain. Although age and joint trauma are prominently associated with OA occurrence, the trigger and signaling pathways propagating their pathogenic aspects are ill defined. Following long-term catabolic activity and traumatic cartilage breakdown, debris accumulates and can trigger Toll-like receptors (TLRs). Here we show that TLR2 stimulation suppressed the expression of matrix proteins and induced an inflammatory phenotype in human chondrocytes. Further, TLR2 stimulation impaired chondrocyte mitochondrial function, resulting in severely reduced adenosine triphosphate (ATP) production. RNA-sequencing analysis revealed that TLR2 stimulation upregulated nitric oxide synthase 2 (NOS2) expression and downregulated mitochondria function-associated genes. NOS inhibition partially restored the expression of these genes, and rescued mitochondrial function and ATP production. Correspondingly, Nos2-/- mice were protected from age-related OA development. Taken together, the TLR2-NOS axis promotes human chondrocyte dysfunction and murine OA development, and targeted interventions may provide therapeutic and preventive approaches in OA.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Altmetric
11.100
0.000
1
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Toll-like Receptors ; Cartilage-anabolic And Catabolic Activities ; Chondrocytes ; Nitric Oxide Synthase ; Osteoarthritis; Toll-like Receptors; Nitric-oxide Synthase; Double-blind; Selective-inhibition; Knee; Progression; Gene; Mice; Differentiation; Chondrogenesis
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Zeitschrift Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Band: 120, Heft: 29, Seiten: , Artikelnummer: e2207993120 Supplement: ,
Verlag National Academy of Sciences
Verlagsort 2101 Constitution Ave Nw, Washington, Dc 20418 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Translational Genomics (ITG)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-506700-001
Förderungen WethankAdrian Madrigal
China Scholarship Council
state of Berlin
European Regional Development Fund (ERDF)
National Natural Science Foundation of China
German Federal Ministry of Education and Research (BMBF)
German Research Foundation (DFG)
Einstein Center for Regenerative Therapies
Dr. Rolf M. Schwiete Foundation
Willy Robert Pitzer Foundation (Pitzer Laboratory of Osteoarthritis Research)
DOI 10.1073/pnas.2207993120
WOS ID 001058459000005
Scopus ID 85164288652
PubMed ID 37428931
Erfassungsdatum 2023-10-06
[➜Korrektur melden]