Mst1/2 Kinases Modulate Glucose Uptake for Osteoblast Differentiation and Bone Formation
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AbstractBone formation and bone homeostasis are energy-expensive processes. How they are being regulated by energy needs is not completely understood. This is of high clinical importance because diabetic-induced bone loss is common whereas the underlying mechanisms are unclear. Here, we show that Mst1/2 are important regulators for glucose uptake during osteoblast differentiation. Genetically removal of both Mst1/2 kinases simultaneously in mice in early and mature osteoblasts inhibits bone formation and bone remodeling, respectively. We found that the activity of Mst1/2 kinases is sensitive to glucose levels, and in turn, regulates glucose uptake by stabilizing key glucose transporter Glut1. In the absence of Mst1/2 kinases, Glut1 expression is loss and results in AMP-dependent protein kinase (AMPK) activation and subsequent proteasomal degradation of Runx2. The streptozotocin (STZ)-induced diabetic mouse model also recapitulates similar changes in the bone tissues. In addition, Glut1 expression regulated by Mst1/2 kinases is independent of Yap/Taz expression. Our results unravel new mechanistic insights into the orchestration of glucose level and bone homeostasis.
All Author(s) ListWenling LI, Yujie DENG, Bo FENG, Kingston King-Lun MAK
Journal nameJournal of Bone and Mineral Research
Volume Number33
Issue Number6
Pages1183 - 1195
LanguagesEnglish-United Kingdom

Last updated on 2020-05-07 at 01:09