Deutsch Intern
    Chair of orthopedic

    Mechanically regulated Genes

    Biomechanics from Wolff´s Law to Molecular Biology

    in Cooperation with the *Department for Traumatological Research and Biomechanics, University of Ulm

    Sigrid Mueller-Deubert
    Melanie Krug
    Regina Ebert
    Franz Jakob

    Mechanical strain affects bone mass and bone architecture. In-vivo, mesenchymal stem cells (MSC) constitute the cellular source for regeneration and healing of bone tissue. While mechanical strain currently is known to stimulate proliferation and matrix synthesis in osteoblastic cells, it is largely unknown, to what extend mechanical forces can influence proliferation and the activation of osteogenic factors in MSC. Concerning this matter, telomerase-immortalized human MSC and respective clones with overexpression and knockdown of cbfa-1, an indispensable transcription factor for osteogenic differentiation, will be submitted to mechanical stretching. The resulting effects will be analyzed comprehensively in terms of proliferation and differentiation. Whole Genome Arrays analyzed be means of bioinformatics will be the starting point for further characterization of selected genes that may have fundamental, tissue-specific impact on mechanotransduction in bone. Identification of such genes in MSC and osteoblast-precursors will provide putative therapeutic target-molecules that might help to recover mechanosensitivity in osteoporotic bone and to maintain bone mass in case of immobilisation and loss of gonadal steroid hormones.

    • Ramani-Mohan RK, Schwedhelm I, Finne-Wistrand A, Krug M, Schwarz T, Jakob F,Walles H, Hansmann J. Deformation strain is the main physical driver for skeletalprecursors to undergo osteogenesis in earlier stages of osteogenic cellmaturation. J Tissue Eng Regen Med. 2017 Sep 5. doi: 10.1002/term.2565. [Epubahead of print]
    • Müller-Deubert S, Seefried L, Krug M, Jakob F, Ebert R. Epidermal growthfactor as a mechanosensitizer in human bone marrow stromal cells. Stem Cell Res. 2017 Oct;24:69-76. doi: 10.1016/j.scr.2017.08.012. Epub 2017 Aug 18.
    • Seefried L, Müller-Deubert S, Krug M, Youssef A, Schütze N, Ignatius A, Jakob F, Ebert R. Dissection of mechanoresponse elements in promoter sites of themechanoresponsive CYR61 gene. Exp Cell Res. 2017 May 15;354(2):103-111. doi:10.1016/j.yexcr.2017.03.031. Epub 2017 Mar 16.
    • Seefried L, Mueller-Deubert S, Schwarz T, Lind T, Mentrup B, Kober M, Docheva D, Liedert A, Kassem M, Ignatius A, Schieker M, Claes L, Wilke W, Jakob F, Ebert R. A small scale cell culture system to analyze mechanobiology using reportergene constructs and polyurethane dishes. Eur Cell Mater. 2010 Dec 10;20:344-55.
    • Liedert A, Wagner L, Seefried L, Ebert R, Jakob F, Ignatius A. Estrogenreceptor and Wnt signaling interact to regulate early gene expression in responseto mechanical strain in osteoblastic cells. Biochem Biophys Res Commun. 2010 Apr 9;394(3):755-9. doi: 10.1016/j.bbrc.2010.03.065. Epub 2010 Mar 17.