Immune Cell Induced Migration of Osteoprogenitor Cells Is Mediated by TGF-β Dependent Upregulation of NOX4 and Activation of Focal Adhesion Kinase

Autor: Sabrina, Ehnert, Caren, Linnemann, Romina H, Aspera-Werz, Daria, Bykova, Sara, Biermann, Leonie, Fecht, Peter M, De Zwart, Andreas K, Nussler, Fabian, Stuby
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 19, Iss 8, p 2239 (2018)
International Journal of Molecular Sciences
Volume 19
Issue 8
ISSN: 1422-0067
Popis: The cytokines secreted by immune cells have a large impact on the tissue, surrounding a fracture, e.g., by attraction of osteoprogenitor cells. However, the underlying mechanisms are not yet fully understood. Thus, this study aims at investigating molecular mechanisms of the immune cell-mediated migration of immature primary human osteoblasts (phOBs), with transforming growth factor beta (TGF-&beta
), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and focal adhesion kinase (FAK) as possible regulators. Monocyte- and macrophage (THP-1 cells ±
phorbol 12-myristate 13-acetate (PMA) treatment)-conditioned media, other than the granulocyte-conditioned medium (HL-60 cells + dimethyl sulfoxide (DMSO) treatment), induce migration of phOBs. Monocyte- and macrophage (THP-1 cells)-conditioned media activate Smad3-dependent TGF-&beta
signaling in the phOBs. Stimulation with TGF-&beta
promotes migration of phOBs. Furthermore, TGF-&beta
treatment strongly induces NOX4 expression on both mRNA and protein levels. The associated reactive oxygen species (ROS) accumulation results in phosphorylation (Y397) of FAK. Blocking TGF-&beta
signaling, NOX4 activity and FAK signaling effectively inhibits the migration of phOBs towards TGF-&beta
In summary, our data suggest that monocytic- and macrophage-like cells induce migration of phOBs in a TGF-&beta
dependent manner, with TGF-&beta
dependent induction of NOX4, associated production of ROS and resulting activation of FAK as key mediators.
Databáze: OpenAIRE
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