Mst1/2 Kinases Modulate Glucose Uptake for Osteoblast Differentiation and Bone Formation.

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Wenling LiKingston King-Lun Mak

Abstract

Bone 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. © 2018 American Society for Bone and Mineral Research.

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Citations

Jul 28, 2020·Current Osteoporosis Reports·Christopher D KegelmanJoel D Boerckel
Feb 6, 2020·Proceedings of the National Academy of Sciences of the United States of America·Xingyao LiStephen B Shears
Apr 8, 2020·Journal of the American Society of Nephrology : JASN·Chunhua XuYin Xia

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