RT Journal Article
SR Electronic
T1 PIP5k1 β controls bone homeostasis through modulating both osteoclast and osteoblast differentiation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 288910
DO 10.1101/288910
A1 Xiaoying Zhao
A1 Guoli Hu
A1 Chuandong Wang
A1 Lei Jiang
A1 Jingyu Zhao
A1 Jiake Xu
A1 Xiaoling Zhang
YR 2018
UL http://biorxiv.org/content/early/2018/03/26/288910.abstract
AB PIP5K1β is crucial to generation of phosphotidylinosotol (4, 5) P2. PIP5K1β participates in numerous cellular activities, such as B cell and platelet activation, cell phagocytosis and endocytosis, cell apoptosis, and cytoskeletal organization. In the present work, we aimed to make insight into the function of PIP5K1β in osteoclastogenesis and osteogenesis to provide promising strategies for osteoporosis prevention and treatment. We discovered that PIP5k1β deletion in mice resulted in obvious bone loss and PIP5K1β was highly expressed both during osteoclast and osteoblast differentiation, besides, PIP5K1β deletion enhanced the proliferation and migration of BMMs to promote osteoclast differentiation. PIP5k1β−/− osteoclast exhibited normal cytoskeleton architecture but stronger resorption activity. PIP5k1β deficiency also promoted activation of MAPK and Akt signaling, enhanced TRAF6 and c-Fos expression, facilitated the expression and nuclear translocation of NFATC1 and upregulated Grb2 expression, thereby accelerating osteoclast differentiation and function. Finally, PIP5K1β enhanced osteoblast differentiation by upregulating master genes expression through triggering smad1/5/8 signaling. Thereby, PIP5K1β modulate bone homeostasis and remodeling.