gms | German Medical Science

Joint German Congress of Orthopaedics and Trauma Surgery

02. - 06.10.2006, Berlin

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NF-κB plays an important role in mesenchymal stem cell invasion in vitro

NF-κB spielt eine wichtige Rolle bei der Invasion von humanen mesenchymalen Stammzellen in vitro

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  • W. Böcker - Department of Surgery - Downtown, University of Munich (LMU), Munich, Germany
  • O. Rossmann - Department of Surgery - Downtown, University of Munich (LMU), Munich, Germany
  • V. Egea-Alonso - Division of Clinical Chemistry and Clinical Biochemistry, University of Munich (LMU), Munich, Germany
  • C. Ries - Division of Clinical Chemistry and Clinical Biochemistry, University of Munich (LMU), Munich, Germany
  • W. Mutschler - Department of Surgery - Downtown, University of Munich (LMU), Munich, Germany
  • M. Schieker - Department of Surgery - Downtown, University of Munich (LMU), Munich, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie. 70. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 92. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie und 47. Tagung des Berufsverbandes der Fachärzte für Orthopädie. Berlin, 02.-06.10.2006. Düsseldorf, Köln: German Medical Science; 2006. DocE.4.1-1572

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgu2006/06dgu0106.shtml

Published: September 28, 2006

© 2006 Böcker et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Background: Several publication have shown, that TNF-α plays an important role in bone healing. The exact molecular mechanisms of stem cell migration and invasion during fracture healing are unknown. Therefore, we have investigated the influence of TNF-α on migration and invasion of human mesenchymal stem cells (hMSCs) and the relevance of the NF-κB signal transduction pathway.

Methods: The dominant-negative mutant of IκB kinase 2 (dn-IKK-2) was over-expressed in hMSCs using lentiviral gene transfer. Green fluorescent protein (eGFP) was used as a negative control. Over-expression of dn-IKK-2 was conformed by RT-PCR and western blot. Inhibition of nuclear translocation of NF-κB (p65) was investigated by immunocytochemistry. Human extracellular matrix was used in invasion and migration assays. Cells were stimulated with 50 ng/ml human recombinant TNF-α

Results: 60% ± 10% of hMSCs were successfully transduced using a lentiviral titer of 1 x 10*4 TU/ml. After blastizidine selection 98% of hMSCs expressed the transgene. TNF-α caused a nuclear translocation of NF-κB (p65) within 30 minutes. Translocation was almost completely blocked by over-expression of dn-IKK-2. Furthermore, TNF-α stimulated the migration and invasion of hMSCs through human extracellular matrix. Overexpression of dn-IKK-2 caused a significant decrease of stem cell migration and invasion.

Conclusion: This study shows for the first time that NF-κB is found in human mesenchymal stem cells and is regulated via IKK-2 after stimulation with TNF-α. Furthermore, we have shown that the NF-κB signal transduction pathway plays a critical role in TNF-α-induced migration of hMSCs. Our results support the hypothesis, that NF-κB signal transduction pathway may plays a critical role in TNF-α-mediated migration of hMSCs during fracture healing.