Understanding mechanotransduction in mesenchymal stem cells by proteomics. Knowledge transfer to implant osseointegration.

Mechanical loading plays an important role in the maintenance and regeneration of bone tissue. The biological mechanisms by which bone adapt to loading are not fully understood. The project aims at investigating the protein expression pattern and their functions during mechanical loading of differentiating cells by means of mass spectrometry and imaging mass spectrometry. In the in vitro part of the project, a cell culture system generating shear stresses and bone marrow mesenchymal stem cells will be used for the investigation of the mechanotransduction process. After selection of the loading condition inducing an optimal differentiation response of mesenchymal stem cells in response to shear stresses, proteomic profiling for different stimulation conditions will be performed by means of 2-D electrophoresis, image analysis, mass spectrometry and bioinformatics (primary sequence databases). The key role of the identified proteins in the pathway of mechanotransduction will be validated through RNA interference. In the in vivo study, imaging mass spectrometry will allow localizing the identified proteins on tissue sections of a well-controlled mechanical loaded implant positioned in the rat tibia. The importance of the bone quality and of specific mechanical parameters will be assessed. New approaches for the treatment of musculoskeletal diseases such as osteoporosis and new biomaterial surface coatings might results from the findings of the project.

Keywords:Proteomics, Differentiation, Mechanotransduction, Mesenchymal stem cells, Implant osseointegration

Disciplines:Dentistry, Morphological sciences, Biochemistry and metabolism, Systems biology, Medical biochemistry and metabolism