BMP2 and mechanical loading cooperatively regulate immediate early signalling events in the BMP pathway

BMC Biology

Research Article

Petra Knaus¹  Jessica Kopf²  Ansgar Petersen³  Georg N Duda³ 

[1] Institute for Chemistry/Biochemistry, FU Berlin, Berlin, Germany;Institute for Chemistry/Biochemistry, FU Berlin, Berlin, Germany;Julius Wolff Institute, Charité-Universitätsmedizin Berlin, Germany;Julius Wolff Institute, Charité-Universitätsmedizin Berlin, Germany;Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany;CMSC, Charité-Universitätsmedizin, Berlin, Germany;

关键词: Mechanical Loading;    Osteogenic Differentiation;    Collagen Scaffold;    Mechanical Boundary Condition;    Mechanotransduction Pathway;   

DOI  :  10.1186/1741-7007-10-37

 received in 2012-04-17, accepted in 2012-04-30,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundEfficient osteogenic differentiation is highly dependent on coordinated signals arising from growth factor signalling and mechanical forces. Bone morphogenetic proteins (BMPs) are secreted proteins that trigger Smad and non-Smad pathways and thereby influence transcriptional and non-transcriptional differentiation cues. Crosstalk at multiple levels allows for promotion or attenuation of signalling intensity and specificity. Similar to BMPs, mechanical stimulation enhances bone formation. However, the molecular mechanism by which mechanical forces crosstalk to biochemical signals is still unclear.ResultsHere, we use a three-dimensional bioreactor system to describe how mechanical forces are integrated into the BMP pathway. Time-dependent phosphorylation of Smad, mitogen-activated protein kinases and Akt in human fetal osteoblasts was investigated under loading and/or BMP2 stimulation conditions. The phosphorylation of R-Smads is increased both in intensity and duration under BMP2 stimulation with concurrent mechanical loading. Interestingly, the synergistic effect of both stimuli on immediate early Smad phosphorylation is reflected in the transcription of only a subset of BMP target genes, while others are differently affected. Together this results in a cooperative regulation of osteogenesis that is guided by both signalling pathways.ConclusionsMechanical signals are integrated into the BMP signalling pathway by enhancing immediate early steps within the Smad pathway, independent of autocrine ligand secretion. This suggests a direct crosstalk of both mechanotransduction and BMP signalling, most likely at the level of the cell surface receptors. Furthermore, the crosstalk of both pathways over longer time periods might occur on several signalling levels.

【 授权许可】

Unknown   
© Kopf et al; licensee BioMed Central Ltd. 2012. 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.