Artikel
Free Fatty Acids Promote Inflammation in Bone
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Autoren
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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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Markus Rickert
- Universitätsklinikum Gießen und Marburg, Orthopädie und Orthopädische Chirurgie, 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
| Veröffentlicht: | 4. September 2017 |
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Gliederung
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Background: Increased amounts of visceral fat are often associated with lower bone density and in obese patients an increased risk of osteoarthritis (OA) can be seen in non-weight bearing joints. Chronically elevated free fatty acid (FFA) levels as occurring in obesity may therefore also play a role in bone loss. We hence analyzed if and how FFA influence active bone cells in rheumatic diseases.
Methods: Primary osteoblasts (OB) were isolated from cancellous bone of OA and rheumatoid arthritis (RA) patients undergoing knee joint surgery. Osteoclasts (OC) were differentiated from peripheral blood mononuclear cells (PBMC). OB and OC were stimulated with the saturated FFA palmitic acid (PA) and the unsaturated FFA linoleic acid (LA). Protein secretion was quantified by immunoassays, mRNA expression by real-time PCR. Mineralization was quantified using Alizarin Red S staining, differentiated OC were quantified by counting TRAP-positive multinuclear cells. Toll-like receptor (TLR) 4 and TLR2 were blocked by neutralizing antibodies.
Results: Stimulation with PA or LA increased OB secretion of the proinflammatory cytokine IL 6 (up to 9-fold ↑) and the chemokines IL-8 (up to 221-fold ↑), GRO-α (from below detection level to detectable levels) and MCP-1 (up to 16-fold ↑). RANKL and OPG were not influenced by FFA on protein and mRNA level. In osteoblasts, activity (ALP/collagen type I) and differentiation markers (e.g. osteocalcin) as well as production of inorganic matrix were not altered significantly by FFA stimulation. TLR4 but not TLR2 blockade reduced PA-induced IL-8 secretion by OB. In both RA and OA OC, IL-8 secretion was enhanced by PA and LA, with a much stronger effect at the earliest time point within the differentiation process for RA OC but not for OA OC. The absolute number of OA OC was mostly increased by PA and decreased by LA. Osteoclast activity markers (CLCN7, CTSK, TCIRG) were not altered in RA OC.
Conclusion: FFA mainly promote inflammation via bone cells, which may indirectly contribute to bone loss. In osteoblasts, FFA signaling appears largely mediated by TLR4, but not by TLR2.
