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

Adipokines affect differentiation of osteoporosis and osteoarthritis spongiosa-derived mesenchymal stromal cells

Meeting Abstract

  • Lali Tsiklauri - Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
  • Janina Werner - Institut für Veterinär-Anatomie, -Histologie und -Embryologie, Justus-Liebig-Universität Gießen, Gießen
  • Klaus Frommer - Justus-Liebig Universität Gießen, Kerckhoff-Klinik GmbH, Rheumatologie u. klinische Immunologie, Osteologie, Physikalische Therapie, Bad Nauheim
  • Ulf Müller-Ladner - 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
  • Sabine Wenisch - Institute of anatomy, histology and embryology, GiessenInstitute of veterinary medicine, Giessen
  • 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.11

doi: 10.3205/16dgrh286, urn:nbn:de:0183-16dgrh2865

Veröffentlicht: 29. August 2016

© 2016 Tsiklauri et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Background: Age-related bone loss and articular cartilage damage are associated with increased bone marrow fat infiltration. A reciprocal relationship between bone marrow adiposity and bone mass has been implicated in osteoporosis. Adipose tissue is metabolically active: It releases proinflammatory (e.g. adipokines) and matrix-degrading proteins (e.g. matrix metalloproteinases, MMPs) which promote progressive bone loss. Moreover, adipocytes and osteoblasts share the same precursor, the mesenchymal stem cell (MSC). The differentiation of MSC into adipocytes or osteoblasts is an important determinant of bone structural integrity. Adipocyte-derived factors might influence differentiation of bone marrow-derived MSCs. Therefore, we analyzed the effects of resistin, leptin and visfatin on MSC-differentiation and their distribution in bone.

Methods: Spongiosa from femoral heads of osteoarthritis patients were collected. Primary spongiosa-derived mesenchymal stromal cells (hMSCs) as well as commercially obtained MSCs were cultured in adipogenic and osteogenic media 3 weeks with/without adipokines. mRNA expression of adipokines, bone marker genes, TIMPs and MMPs of stimulated hMSCs/MSCs as well as of bone samples were evaluated by real time PCR. The secretion of pro-inflammatory mediators was determined by ELISA.

Results: Expression of visfatin and leptin was significantly increased in osteoporotic bone (n=14) compared to non-osteoporotic bone (n=14). The stimulation with visfatin of hMSC during adipogenic differentiation markedly increased MMP13-expression (e.g. d21: 72-fold) but not leptin and resistin. In osteogenic differentiated cells, a reduction of MMP2 by stimulation of all adipokines could be observed (n=3). However, the expression of MMP13 was downregulated mainly by visfatin (e.g. d21: 55-fold). In addition, visfatin decreased TIMP1 (e.g. d21: 2.9-fold), TIMP2 (e.g. d21: 3.2-fold), and RunX2 (e.g. d21: 5.9-fold) production and overall matrix production in contrast to leptin and resistin during osteogenic differentiation. Moreover, visfatin induced the secretion of IL-6, IL-8 and MCP-1 in both, osteogenic and adipogenic differentiated cells.

Conclusion: Visfatin and leptin levels are increased in osteoporotic bone. The altered MMP and TIMP production mediated especially by visfatin might influence bone remodeling at the bone/bone marrow interface. Although leptin had no local effect on MSCs differentiation in vitro, it may modulate bone degradation by affecting other cell types such as inflammatory cells.