gms | German Medical Science

44. Kongress der Deutschen Gesellschaft für Rheumatologie, 30. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 26. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

31.08. - 03.09.2016, Frankfurt am Main

Divergent Effects of Free Fatty Acids on Cells of Bone Metabolism

Meeting Abstract

  • Klaus Frommer - Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
  • Andreas Schäffler - Justus-Liebig-University of Giessen, Department of Internal Medicine III, Endocrinology, Diabetes, Metabolism, Giessen
  • Uwe Lange - Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
  • Stefan Rehart - Agaplesion Markus Krankenhaus, Akademisches Lehrkrankenhaus der Johann Wolfgang Goethe-Universität, Klinik für Orthopädie und Unfallchirurgie, Frankfurt/Main
  • Jürgen Steinmeyer - Universitätsklinikum Gießen und Marburg, Orthopädische Klinik, Labor für Experimentelle Orthopädie, Gießen
  • Markus Rickert - Universitätsklinikum Gießen und Marburg, Orthopädie und Orthopädische Chirurgie, Gießen
  • Ulf Müller-Ladner - Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
  • Elena Neumann - Justus-Liebig-Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 44. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 30. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 26. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Frankfurt am Main, 31.08.-03.09.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocER.01

doi: 10.3205/16dgrh044, urn:nbn:de:0183-16dgrh0443

Published: August 29, 2016

© 2016 Frommer et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Background: Obesity is associated with an increased risk of osteoarthritis also in non-weight bearing joints and increased amounts of visceral fat are associated with lower bone density. Furthermore, chronically elevated free fatty acid (FFA) serum levels are linked to a number of inflammatory cardiovascular and metabolic diseases. These observations suggest that FFA may also play a role in inflammation-related bone loss. The influence of FFA on cells of bone metabolism however has not been investigated yet. We analyzed the effect of FFA on osteoblasts and osteoclasts in the context of rheumatic diseases.

Methods: Primary osteoblasts were isolated from cancellous bone of rheumatoid arthritis (RA) and osteoarthritis (OA) patients undergoing knee joint surgery. Osteoblasts were stimulated with palmitic acid (PA) as a saturated and linoleic (LA) acid as an unsaturated FFA. Immunoassays were used to quantify protein secretion. mRNA expression was quantified by real-time PCR. Mineralization activity was analyzed by alizarin red S staining of mineralized matrix. Osteoclastogenesis of monocytic precursor cells was quantified by counting the number of differentiated osteoclasts defined as TRAP-positive multinucleated cells. Toll-like receptors (TLR) 2 and 4 were blocked by neutralizing antibodies.

Results: Both PA and LA increased the secretion of the proinflammatory cytokine IL-6 (up to 9-fold) and the chemokines IL-8 (up to 221-fold), GRO-α and MCP-1. The extent of the response was highly dependent on the donor. Markers of osteoblast activity (ALP, collagen type I) and osteoblast differentiation (e.g. osteocalcin) as well as RANKL and OPG, mediators of osteoclastogenesis and osteoclast activity, were not affected by FFA at mRNA or protein level. The PA-induced IL-8 secretion could be significantly reduced by blocking TLR4 but not TLR2. RA osteoclasts responded to PA and LA stimulation with a decrease in the number of TRAP-positive multinucleated cells. However, markers of osteoclast activity (CLCN7, CTSK, TCIRG) remained unchanged.

Conclusion: The effect of FFA on cells of bone metabolism appears to be divergent. Their proinflammatory effect via osteoblasts could indirectly promote bone resorption, while the reduced formation of differentiated osteoclasts might contribute to an increase in bone density.