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  Investigation of arthritic joint destruction by a novel fibroblast-based model.

Sack, U., Sehm, B., Kahlenberg, F., Murr, A., Lehmann, J., Tannapfel, A., et al. (2005). Investigation of arthritic joint destruction by a novel fibroblast-based model. Annals of the New York Academy of Sciences, 1051, 291-298. doi:10.1196/annals.1361.070.

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 Creators:
Sack, Ulrich1, Author
Sehm, Bernhard1, Author              
Kahlenberg, F.1, Author
Murr, A.1, Author
Lehmann, J.2, Author
Tannapfel, A.3, Author
Uberla, K.4, Author
Moessner , A.5, Author
Dietrich, A.6, Author
Emmrich, F.1, Author
Lange, F.1, Author
Jungel, A.1, Author
Braun, J.-M.1, Author
Anderegg, U.7, Author
Affiliations:
1Medical Faculty, Institute of Clinical Immunology and Transfusion Medicine, University of Leipzig , Johannisallee 30, 04103 Leipzig, Germany, ou_persistent22              
2Labor Diagnostik GmbH Leipzig, Research and Development , Leipzig, Germany, ou_persistent22              
3Institute of Pathology, University of Leipzig, Leipzig, Germany, ou_persistent22              
4Medical Faculty, Department of Molecular and Medical Virology, University of Bochum, 44801 Bochum, Germany, ou_persistent22              
5Department of Ophthalmology, University of Leipzig, Leipzig, Germany, ou_persistent22              
6Department of Surgery, University of Leipzig, Leipzig, Germany, ou_persistent22              
7Department of Clinic of Dermatology, Leipzig, Germany, ou_persistent22              

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 Abstract: The key pathologic mechanism in rheumatoid arthritis (RA) is the destruction of cartilage by fibroblasts. In a severe combined immunodeficient (SCID) mouse model, this process can be modulated by gene transfer using invasive LS48 fibroblasts. This study aims to investigate the effect of interleukins (IL) -11 and -12 on cartilage destruction when transferred into LS48, and of IL-15 when transfected into non-invasive 3T3 cells; to compare three transduction systems (a lentiviral vector system, a retroviral vector system, and a particle-mediated gene transfer); and to establish an in vitro cartilage destruction system based on LS48 cells. Transduced fibroblasts were injected into SCID mice knee joints, and disease progression assessed microscopically. Distinctive morphologic pattern revealed invasion of fibroblasts into the articular cartilage by transfected, as well as non-transfected, LS48 cells. IL-12 and IL-15 did not alter swelling or cartilage destruction. Animals treated with IL-11-transfected cells showed reduced cartilage damage but no changes in swelling. Efficacy of gene transfer to establish transfected fibroblasts was shown to be >85% for lentiviral transfer, compared to <10% for retroviral transfer and gene gun. Furthermore, cells were co-incubated with porcine cartilage. Transduction of IL-11 led to a reduction of apoptosis in chondrocytes. These findings suggest that cartilage destruction by invasive fibroblasts can be modulated by gene transfer. Lentiviral vector systems offer the most effective approach for gene transduction. In vitro fibroblast/cartilage co-cultures present a convenient system for the assessment of novel therapeutic strategies toward reduction of articular destruction.

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 Dates: 2005
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: DOI: 10.1196/annals.1361.070
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Title: Annals of the New York Academy of Sciences
  Other : Ann. N.Y. Acad. Sci.
Source Genre: Journal
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Publ. Info: New York : New York Academy of Sciences
Pages: - Volume / Issue: 1051 Sequence Number: - Start / End Page: 291 - 298 Identifier: ISSN: 0077-8923
CoNE: https://pure.mpg.de/cone/journals/resource/954926958894_2