Mechano-transduction in periodontal ligament cells identifies activated states of MAP-kinases p42/44 and p38-stress kinase as a mechanism for MMP-13 expression

BMC Cell Biology

Research Article

Pascal Tomakidi¹  Thorsten Steinberg¹  Simon Schulz¹  Nelli Ziegler²  Eva Müssig³  Annette Kohl⁴  Dale Woodnutt⁴  Angel Alonso⁵ 

[1] Department of Oral Biotechnology, Dental School, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany;Department of Oral Biotechnology, Dental School, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany;Department of Orthodontics and Dentofacial Orthopaedics, Dental School, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany;Department of Oral Biotechnology, Dental School, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany;Department of Orthodontics, Dental School, University of Freiburg, Hugstetterstrasse 55, 79106, Freiburg, Germany;Department of Orthodontics and Dentofacial Orthopaedics, Dental School, University of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany;Division of Cell Differentiation, German Cancer Research Center, Im Neuenheimer Feld 242, 69120, Heidelberg, Germany;

关键词: Focal Adhesion Kinase;    Focal Adhesion;    Strain Application;    Periodontal Ligament;    Integrin Subunit;   

DOI  :  10.1186/1471-2121-11-10

 received in 2009-06-29, accepted in 2010-01-28,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundMechano-transduction in periodontal ligament (PDL) cells is crucial for physiological and orthodontic tooth movement-associated periodontal remodelling. On the mechanistic level, molecules involved in this mechano-transduction process in PDL cells are not yet completely elucidated.ResultsIn the present study we show by western blot (WB) analysis and/or indirect immunofluorescence (IIF) that mechanical strain modulates the amount of the matrix metalloproteinase MMP-13, and induces non-coherent modulation in the amount and activity of signal transducing molecules, such as FAK, MAP-kinases p42/44, and p38 stress kinase, suggesting their mechanistic role in mechano-transduction. Increase in the amount of FAK occurs concomitant with increased levels of the focal contact integrin subunits β3 and β1, as indicated by WB or optionally by IIF. By employing specific inhibitors, we further identified p42/44 and p38 in their activated, i.e. phosphorylated state responsible for the expression of MMP-13. This finding may point to the obedience in the expression of this MMP as extracellular matrix (ECM) remodelling executioner from the activation state of mechano-transducing molecules. mRNA analysis by pathway-specific RT-profiler arrays revealed up- and/or down-regulation of genes assigning to MAP-kinase signalling and cell cycle, ECM and integrins and growth factors. Up-regulated genes include for example focal contact integrin subunit α3, MMP-12, MAP-kinases and associated kinases, and the transcription factor c-fos, the latter as constituent of the AP1-complex addressing the MMP-13 promotor. Among others, genes down-regulated are those of COL-1 and COL-14, suggesting that strain-dependent mechano-transduction may transiently perturbate ECM homeostasis.ConclusionsStrain-dependent mechano-/signal-transduction in PDL cells involves abundance and activity of FAK, MAP-kinases p42/44, and p38 stress kinase in conjunction with the amount of MMP-13, and integrin subunits β1 and β3. Identifying the activated state of p42/44 and p38 as critical for MMP-13 expression may indicate the mechanistic contribution of mechano-transducing molecules on executioners of ECM homeostasis.

【 授权许可】

Unknown   
© Ziegler et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.