JNK1 is not essential for TNF-mediated joint disease
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JNK1 is not essential for TNF-mediated joint disease. / Köller, Marcus; Hayer, Silvia; Redlich, Kurt; Ricci, Romeo; David, Jean-Pierre; Steiner, Günter; Smolen, Josef S; Wagner, Erwin F; Schett, Georg.
in: ARTHRITIS RES THER, Jahrgang 7, Nr. 1, 01.01.2005, S. R166-73.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - JNK1 is not essential for TNF-mediated joint disease
AU - Köller, Marcus
AU - Hayer, Silvia
AU - Redlich, Kurt
AU - Ricci, Romeo
AU - David, Jean-Pierre
AU - Steiner, Günter
AU - Smolen, Josef S
AU - Wagner, Erwin F
AU - Schett, Georg
PY - 2005/1/1
Y1 - 2005/1/1
N2 - Tumour necrosis factor (TNF) signalling molecules are considered as promising therapeutic targets of antirheumatic therapy. Among them, mitogen-activated protein kinases are thought to be of central importance. Herein, we investigate the role in vivo of TNF-alpha signalling through c-Jun N-terminal kinase (JNK)1 in destructive arthritis. Human TNF transgenic (hTNFtg) mice, which develop inflammatory arthritis, were intercrossed with JNK1-deficient (JNK1-/-) mice. Animals (n = 35) of all four genotypes (wild-type, JNK1-/-, hTNFtg, JNK1-/-hTNFtg) were assessed for clinical and histological signs of arthritis. Clinical features of arthritis (swelling and decreased grip strength) developed equally in hTNFtg and JNK1-/-hTNFtg mice. Histological analyses revealed no differences in the quantity of synovial inflammation and bone erosions or in the cellular composition of the synovial infiltrate. Bone destruction and osteoclast formation were observed to a similar degree in hTNFtg and JNK1-/-hTNFtg animals. Moreover, cartilage damage, as indicated by proteoglycan loss in the articular cartilage, was comparable in the two strains. Intact phosphorylation of JNK and c-Jun as well as expression of JNK2 in the synovial tissue of JNK1-/-hTNFtg mice suggests that signalling through JNK2 may compensate for the deficiency in JNK1. Thus, JNK1 activation does not seem to be essential for TNF-mediated arthritis.
AB - Tumour necrosis factor (TNF) signalling molecules are considered as promising therapeutic targets of antirheumatic therapy. Among them, mitogen-activated protein kinases are thought to be of central importance. Herein, we investigate the role in vivo of TNF-alpha signalling through c-Jun N-terminal kinase (JNK)1 in destructive arthritis. Human TNF transgenic (hTNFtg) mice, which develop inflammatory arthritis, were intercrossed with JNK1-deficient (JNK1-/-) mice. Animals (n = 35) of all four genotypes (wild-type, JNK1-/-, hTNFtg, JNK1-/-hTNFtg) were assessed for clinical and histological signs of arthritis. Clinical features of arthritis (swelling and decreased grip strength) developed equally in hTNFtg and JNK1-/-hTNFtg mice. Histological analyses revealed no differences in the quantity of synovial inflammation and bone erosions or in the cellular composition of the synovial infiltrate. Bone destruction and osteoclast formation were observed to a similar degree in hTNFtg and JNK1-/-hTNFtg animals. Moreover, cartilage damage, as indicated by proteoglycan loss in the articular cartilage, was comparable in the two strains. Intact phosphorylation of JNK and c-Jun as well as expression of JNK2 in the synovial tissue of JNK1-/-hTNFtg mice suggests that signalling through JNK2 may compensate for the deficiency in JNK1. Thus, JNK1 activation does not seem to be essential for TNF-mediated arthritis.
KW - Animals
KW - Arthritis, Experimental
KW - Bone and Bones
KW - Cartilage, Articular
KW - Crosses, Genetic
KW - Genotype
KW - Humans
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Mice, Transgenic
KW - Mitogen-Activated Protein Kinase 8
KW - Mitogen-Activated Protein Kinase 9
KW - Osteoclasts
KW - Phosphorylation
KW - Protein Processing, Post-Translational
KW - Proteoglycans
KW - Proto-Oncogene Proteins c-jun
KW - Recombinant Fusion Proteins
KW - Signal Transduction
KW - Single-Blind Method
KW - Synovial Membrane
KW - Tumor Necrosis Factor-alpha
U2 - 10.1186/ar1473
DO - 10.1186/ar1473
M3 - SCORING: Journal article
C2 - 15642137
VL - 7
SP - R166-73
JO - ARTHRITIS RES THER
JF - ARTHRITIS RES THER
SN - 1478-6354
IS - 1
ER -