gms | German Medical Science

42. Kongress der Deutschen Gesellschaft für Rheumatologie, 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie, 24. Wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie

17.-20. September 2014, Düsseldorf

Vitamin D hormone prevents TNF-alpha effects on expression of osteogenic markers and on NFκB activation in human osteoblasts

Meeting Abstract

  • Peter Oelzner - Universitätsklinikum Jena, Klinik für Innere Medizin III, Abt. Rheumatologie/Osteologie, Jena
  • Sybille Franke - Universitätsklinikum Jena, Klinik für Innere Medizin III, Abt. Rheumatologie/Osteologie, Jena
  • Tzvetanka Bondeva - Universitätsklinikum Jena, Klinik für Innere Medizin III, Jena
  • Gunther Hofmann - Universitätsklinikum Jena, Klinik für Unfall-, Hand- und Wiederherstellungschirurgie, Jena
  • Gunter Wolf - Universitätsklinikum Jena, Klinik für Innere Medizin III, Jena

Deutsche Gesellschaft für Rheumatologie. Deutsche Gesellschaft für Orthopädische Rheumatologie. Gesellschaft für Kinder- und Jugendrheumatologie. 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR). Düsseldorf, 17.-20.09.2014. Düsseldorf: German Medical Science GMS Publishing House; 2014. DocER.01

doi: 10.3205/14dgrh068, urn:nbn:de:0183-14dgrh0688

Veröffentlicht: 12. September 2014

© 2014 Oelzner et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Background: By suppression of bone formation and stimulation of bone resorption TNF-α is of critical importance in inflammation associated bone destruction and inflammation associated osteoporosis. On the other hand, chronic inflammatory diseases are frequently associated with vitamin D deficiency. The active vitamin D hormone (1,25D3) has been shown to have protective effects on bone loss especially on the background of chronic inflammation. The aim of our study was to investigate, if 1,25D3 is able to antagonize unfavourable TNF-α effects on human osteoblasts (OB).

Methods: Human OB were isolated and cultured from bone tissue of 3 individual patients with knee osteoarthritis and joint replacement. Cells from passages 3-7 were treated for 14 days with 10 % FCS, TNF-α (1 ng/ml and 10 ng/ml), 1,25D3 (5*10-10 Mol/l) and with the combination of TNF-α and 1,25D3. MRNA and protein expression of the osteogenic markers bone alkaline phosphatase (bALP), collagen type 1 (Col1) and osteocalcin (OC) as well as of receptor of advanced glycation end products (RAGE) and NFκBp65 were investigated by real-time PCR and Western Blot-analysis, respectively. Furthermore, protein expression of IκB and phosphorylated IκB (pIκB) was measured. Electrophoretic mobility shift assay (EMSA) was performed to investigate NFκB DNA-binding activity.

Results: In comparison to untreated human OB, TNF-α treatment resulted in a significant suppression of mRNA and protein expression of bALP, Col1 and OC and a significant decrease of RAGE and NFκBp65 mRNA expression. RAGE protein expression was not influenced by TNF-α and NFκBp65 protein expression was numerically increased. TNF-α induced a significant increase of the pIκB/IκB ratio (protein expression) and resulted in NFκBp65 activation. In contrast to TNF-α, 1,25D3 significantly upregulated the mRNA and protein expression of bALP, Col1 and OC. RAGE and NFκBp65 mRNA and protein expression as well as the pIκB/IB ratio were not significantly influenced by 1,25D3. The combination of 1,25D3 with TNF-α resulted in a complete inhibition of TNF-α induced NFκB activation and normalization of the expression of the osteogenic markers.

Conclusion: 1,25D3 prevents anti-osteogenic effects of TNF-α on human OB, probably by inhibition of TNF-α induced NFκB activation.