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JNK1 is not essential for TNF-mediated joint disease.

Köller M, Hayer S, Redlich K, Ricci R, David JP, Steiner G, Smolen JS, Wagner EF, Schett G - Arthritis Res. Ther. (2004)

Bottom Line: 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.

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Affiliation: Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Austria. Marcus.Koeller@meduniwien.ac.at

ABSTRACT
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.

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Quantitative analysis of synovial inflammation and joint destruction. There were no differences in the extent of inflammatory tissue between human tumour necrosis factor transgenic (hTNFtg) and intercrossed (JNK1-/-hTNFtg) mice. Mean areas of inflammation (a) and erosions (b) were comparable in these two strains. Vertical bars indicate standard deviation. JNK, c-Jun N-terminal kinase.
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Figure 3: Quantitative analysis of synovial inflammation and joint destruction. There were no differences in the extent of inflammatory tissue between human tumour necrosis factor transgenic (hTNFtg) and intercrossed (JNK1-/-hTNFtg) mice. Mean areas of inflammation (a) and erosions (b) were comparable in these two strains. Vertical bars indicate standard deviation. JNK, c-Jun N-terminal kinase.

Mentions: We next more closely evaluated arthritis by quantitative and qualitative histological analysis of inflammatory tissue (Fig. 2). Animals of both control groups, wt and JNK1-/-, did not show any sign of joint inflammation or destruction. In contrast, hTNFtg mice not only developed intense inflammation but also showed multiple bone erosions. Comparable destructive changes were observed in joints from JNK1-/-hTNFtg mice. Quantitative analysis of the area of synovial inflammation revealed no significant differences between hTNFtg and JNK1-/-hTNFtg mice (Fig. 3a). Similarly, quantification of erosive changes was comparable in these two genotypes (Fig. 3b). Furthermore, immunohistochemical analysis revealed similar distributions of T cells, B cells, granulocytes, and macrophages within the synovial membranes of the two genotypes (Table 1).


JNK1 is not essential for TNF-mediated joint disease.

Köller M, Hayer S, Redlich K, Ricci R, David JP, Steiner G, Smolen JS, Wagner EF, Schett G - Arthritis Res. Ther. (2004)

Quantitative analysis of synovial inflammation and joint destruction. There were no differences in the extent of inflammatory tissue between human tumour necrosis factor transgenic (hTNFtg) and intercrossed (JNK1-/-hTNFtg) mice. Mean areas of inflammation (a) and erosions (b) were comparable in these two strains. Vertical bars indicate standard deviation. JNK, c-Jun N-terminal kinase.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1064897&req=5

Figure 3: Quantitative analysis of synovial inflammation and joint destruction. There were no differences in the extent of inflammatory tissue between human tumour necrosis factor transgenic (hTNFtg) and intercrossed (JNK1-/-hTNFtg) mice. Mean areas of inflammation (a) and erosions (b) were comparable in these two strains. Vertical bars indicate standard deviation. JNK, c-Jun N-terminal kinase.
Mentions: We next more closely evaluated arthritis by quantitative and qualitative histological analysis of inflammatory tissue (Fig. 2). Animals of both control groups, wt and JNK1-/-, did not show any sign of joint inflammation or destruction. In contrast, hTNFtg mice not only developed intense inflammation but also showed multiple bone erosions. Comparable destructive changes were observed in joints from JNK1-/-hTNFtg mice. Quantitative analysis of the area of synovial inflammation revealed no significant differences between hTNFtg and JNK1-/-hTNFtg mice (Fig. 3a). Similarly, quantification of erosive changes was comparable in these two genotypes (Fig. 3b). Furthermore, immunohistochemical analysis revealed similar distributions of T cells, B cells, granulocytes, and macrophages within the synovial membranes of the two genotypes (Table 1).

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Internal Medicine III, Division of Rheumatology, Medical University of Vienna, Austria. Marcus.Koeller@meduniwien.ac.at

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus