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Experimental models of arthritis in which pathogenesis is dependent on TNF expression

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Abstract

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by joint damage as well as systemic manifestations. The exact cause of RA is not known. Both genetic and environmental factors are believed to contribute to the development of this disease. Increased expression of tumor necrosis factor (TNF) has been implicated in the pathogenesis of RA. Currently, the use of anti-TNF drugs is one of the most effective strategies for the treatment of RA, although therapeutic response is not observed in all patients. Furthermore, due to non-redundant protective functions of TNF, systemic anti-TNF therapy is often associated with unwanted side effects such as increased frequency of infectious diseases. Development of experimental models of arthritis in mice is necessary for studies on the mechanisms of pathogenesis of this disease and can be useful for comparative evaluation of various anti-TNF drugs. Here we provide an overview of the field and present our own data with two experimental models of autoimmune arthritis — collagen-induced arthritis and antibody-induced arthritis in C57Bl/6 and BALB/c mice, as well as in tnf-humanized mice generated on C57Bl/6 back-ground. We show that TNF-deficient mice are resistant to the development of collagen-induced arthritis, and the use of anti-TNF therapy significantly reduces the disease symptoms. We also generated and evaluated a fluorescent detector of TNF overexpression in vivo. Overall, we have developed an experimental platform for studying the mechanisms of action of existing and newly developed anti-TNF drugs for the treatment of rheumatoid arthritis.

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, 119991, Moscow, Russia

    M. S. Drutskaya, G. A. Efimov, R. V. Zvartsev, A. A. Chashchina & S. A. Nedospasov

  2. Biological Faculty, Lomonosov Moscow State University, Leninsky Gory 1/12, 119234, Moscow, Russia

    A. A. Chashchina, S. V. Tillib & S. A. Nedospasov

  3. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia

    D. M. Chudakov

  4. Institute of Gene Biology, Russian Academy of Sciences, ul. Vavilova 34/5, 119334, Moscow, Russia

    S. V. Tillib

  5. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninsky Gory 1/40, 119234, Moscow, Russia

    A. A. Kruglov & S. A. Nedospasov

  6. Lobachevsky State University of Nizhnii Novgorod, pr. Gagarina 23, 603950, Nizhnii Novgorod, Russia

    A. A. Kruglov & S. A. Nedospasov

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  1. M. S. Drutskaya
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  2. G. A. Efimov
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  3. R. V. Zvartsev
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  4. A. A. Chashchina
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  5. D. M. Chudakov
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  6. S. V. Tillib
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  7. A. A. Kruglov
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  8. S. A. Nedospasov
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Correspondence to M. S. Drutskaya.

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Published in Russian in Biokhimiya, 2014, Vol. 79, No. 12, pp. 1648–1657.

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Drutskaya, M.S., Efimov, G.A., Zvartsev, R.V. et al. Experimental models of arthritis in which pathogenesis is dependent on TNF expression. Biochemistry Moscow 79, 1349–1357 (2014). https://doi.org/10.1134/S0006297914120086

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