TY  - JOUR
A1  - Müller-Deubert, Sigrid
A1  - Seefried, Lothar
A1  - Krug, Melanie
A1  - Jakob, Franz
A1  - Ebert, Regina
T1  - Epidermal growth factor as a mechanosensitizer in human bone marrow stromal cells
T2  - Stem Cell Research
N2  - Epidermal growth factors (EGFs) e.g. EGF, heparin-binding EGF and transforming growth factor alpha and their receptors e.g. EGFR and ErbB2 control proinflammatory signaling and modulate proliferation in bone marrow stromal cells (BMSC). Interleukin-6 and interleukin-8 are EGF targets and participate in the inflammatory phase of bone regeneration via non-canonical wnt signaling. BMSC differentiation is also influenced by mechanical strain-related activation of ERK1/2 and AP-1, but the role of EGFR signaling in mechanotransduction is unclear. We investigated the effects of EGFR signaling in telomerase-immortalized BMSC, transfected with a luciferase reporter, comprising a mechanoresponsive AP1 element, using ligands, neutralizing antibodies and EGFR inhibitors on mechanotransduction and we found that EGF via EGFR increased the response to mechanical strain. Results were confirmed by qPCR analysis of mechanoresponsive genes. EGF-responsive interleukin-6 and interleukin-8 were synergistically enhanced by EGF stimulation and mechanical strain. We show here in immortalized and primary BMSC that EGFR signaling enhances mechanotransduction, indicating that the EGF system is a mechanosensitizer in BMSC. Alterations in mechanosensitivity and -adaptation are contributors to age-related diseases like osteoporosis and the identification of a suitable mechanosensitizer could be beneficial. The role of the synergism of these signaling cascades in physiology and disease remains to be unraveled.
KW  - mechanotransduction
KW  - bone marrow stromal cells
KW  - epidermal growth factor
KW  - signaling
Y1  - 2017
UR  - https://opus.bibliothek.uni-wuerzburg.de/frontdoor/index/index/docId/17024
UR  - https://nbn-resolving.org/urn:nbn:de:bvb:20-opus-170247
VL  - 24
ER  -