Article
Pro-inflammatory effect of free fatty acids on bone-forming cells
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Authors
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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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Andreas Schäffler
- Justus-Liebig-University of Giessen, Department of Internal Medicine III, Endocrinology, Diabetes, Metabolism, Giessen
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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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Stefan Rehart
- Agaplesion Markus Krankenhaus, Akademisches Lehrkrankenhaus der Johann Wolfgang Goethe-Universität, Klinik für Orthopädie und Unfallchirurgie, Frankfurt/Main
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Jürgen Steinmeyer
- Universitätsklinikum Gießen und Marburg, Orthopädische Klinik, Labor für Experimentelle Orthopädie, Gießen
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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
| Published: | September 1, 2015 |
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Outline
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Introduction: Inflammation and chronically elevated free fatty acid (FFA) levels are linked to each other under several pathological conditions. However, the influence of FFA on cells of bone metabolism is largely unknown so far. The fact that obesity is associated with a higher risk of osteoarthritis also in non-weight bearing joints suggests that FFA may also play a role in bone metabolism. In addition, the FFA mediated signaling was evaluated in osteoblasts.
To test the hypothesis that FFA affect cells of bone metabolism in the context of rheumatic diseases. Specifically bone-forming cells, i.e. osteoblasts, were analyzed. A further objective was to examine whether TLR signaling is involved in FFA-mediated effects in osteoblasts.
Methods: Primary osteoblasts were isolated from cancellous bone of rheumatoid arthritis (RA) and osteoarthritis (OA) patients undergoing knee joint surgery. The osteoblasts were stimulated with saturated and unsaturated FFA of different length. Immunoassays were used to quantify protein secretion. mRNA expression levels were quantified by real-time PCR. TLR2 and TLR4 were blocked using neutralizing antibodies.
Results: FFA-stimulated osteoblasts secreted increased amounts of the proinflammatory cytokine IL-6 and the chemokine IL-8 in a donor-dependent manner (IL-6: up to 9.1-fold; IL-8: up to 221-fold). RANKL and OPG, important regulators of osteoclastogenesis and osteoclast activity, were not affected by FFA on protein as well as mRNA level. Osteoblast activity markers (ALP and collagen type I), markers of osteoblast differentiation (SOX9, RunX2, osterix, osteocalcin), and Wnt signaling molecules (axin-2 and β-catenin) also remained unchanged by FFA stimulation on mRNA level. Both, saturated (e.g. palmitic acid) and unsaturated (e.g. linoleic acid) FFA, caused a pro-inflammatory response in osteoblasts. Blocking of TLR4 but not TLR2 reduced the FFA-induced IL-6 secretion in osteoblasts.
Conclusion: Inflammation plays a key role in many rheumatic diseases and increased inflammatory activity is associated with degradation of bone. Locally increased FFA levels may promote inflammation by altering the secretory profile of osteoblasts via TLR4. However, FFA appear not to affect osteoblast function directly.
