Artikel
Effect of adipokines on Wnt signaling in osteoarthritis osteoblasts
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Autoren
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Susann Junker
- Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Grit Krumbholz
- Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Klaus Frommer
- Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Stefan Rehart
- Agaplesion Markus Krankenhaus, Akademisches Lehrkrankenhaus der Johann Wolfgang Goethe-Universität, Klinik für Orthopädie und Unfallchirurgie, Frankfurt/Main
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Uwe Lange
- Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Georg Schett
- Universitätsklinikum Erlangen, Medizinische Klinik 3, Rheumatologie und Immunologie, Erlangen
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Ulf Müller-Ladner
- Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
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Elena Neumann
- Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
| Veröffentlicht: | 12. September 2014 |
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Gliederung
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Background: Osteoarthritis (OA) is characterized by cartilage and bone erosion but also by osteophyte formation that is mediated by an increased osteoblast activity which is regulated by the Wnt signaling pathway. Obesity is a recognized risk factor in OA, but there is limited information about the interaction between bone formation and adipose tissue-derived factors including adipokines. Histological analysis of OA osteophytes showed the presence of adiponectin, resistin and visfatin in osteophytes. Additionally, OA osteoblasts respond to adipokines in a specific manner, e.g. adiponectin induces inflammatory mediators in osteoblasts. These effects can be further modulated by activation of the Wnt-signaling pathway. Hence, in this context, the effects of adiponectin, resistin and visfatin on Wnt signaling in OA osteoblasts were analyzed.
Methods: Osteoblasts were isolated from OA bone tissue obtained during joint replacement surgery. Cultured osteoblasts were stimulated with adiponectin, resistin and visfatin and additionally, a co-stimulation with Wnt3a or DKK1 was performed. The Wnt signaling pathway of stimulated vs. non-stimulated osteoblasts was analyzed for adipokine-mediated effects using immunoassays for IL-6, DKK1 and sclerostin, and by real-time PCR for axin2.
Results: Stimulation of OA osteoblasts with adiponectin, resistin or visfatin did not alter the release of the Wnt inhibitor DKK1 compared to the unstimulated controls. Secreted Wnt inhibitor sclerostin levels were below the detection level of the immunoassay for both, adipokine-stimulated osteoblasts as well as unstimulated control cells. Also, the expression of axin2, a direct target gene of the Wnt signaling, showed no significant differences in OA osteoblasts after adipokine-stimulation compared to the unstimulated control. A co-stimulation with adiponectin, resistin or visfatin in combination with Wnt3a or DKK1 had no synergistic influence on the Wnt-mediated IL-6 release of OA osteoblasts.
Conclusion: The adipokines adiponectin, resistin and visfatin are present in osteoblasts in OA osteophytes, and adipokines such as adiponectin increase the release of inflammatory mediators by OA osteoblasts. Nevertheless, the observed adipokine-mediated effects do not include alteration of Wnt-signaling and are -in turn- not induced via Wnt-pathway activation. Therefore, the involvement of adipokines specifically in OA osteophyte formation via osteoblasts appears to be independent of Wnt signaling.
