What is it about?
Having shown a role of the MEK5/ERK5/KLF pathway as mediators of cholesterol-decreasing statins before (Ohnesorge et. al., J. Biol. Chem. 2010; 285: 26199–26210), we now reveal that this pathway is also activated by bone-sustaining bisphosphonates that represent other inhibitors of the mevalonate pathway used for osteoporosis treatment. We also demonstrate a critical role of ERK5 activity in osteogenic differentiation and mineralization of human mesenchymal stem cells by KLF2-dependent regulation of bone-relevant genes such as Parathyroid like Hormone (PTHLH). Further we provide evidence for an inverse correlation of ERK5 phosphorylation and activity of Cdc42 suggesting that ERK5 activation by mevalonate pathway inhibiting drugs is due to functional inactivation of Cdc42 by interference with ist prenylation.
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Why is it important?
- We reveal the mechanism of ERK5 actvation by mevalonate pathway-inhibiting drugs - We show a critical role of ERK5 in osteogenic differntiation and mineralization - We demonstrate that Cdc42 inhibition results in ERK5 activation
Perspectives
Modulation of ERK5 activity may be a strategy for treating bone-related diseases including osteoporosis
Professor Marc Schmidt
University of Würzburg
Read the Original
This page is a summary of: The MEK5/ERK5 mitogen-activated protein kinase cascade is an effector pathway of bone-sustaining bisphosphonates that regulates osteogenic differentiation and mineralization, Bone, June 2018, Elsevier,
DOI: 10.1016/j.bone.2018.03.020.
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