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bioRxiv · 10.1101/288910

PIP5k1 β controls bone homeostasis through modulating both osteoclast and osteoblast differentiation

Zhao, X.-y.·Hu, G.·Wang, C.·Jiang, L.·Zhao, J.·Xu, J.·Zhang, X.
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Abstract

PIP5K1{beta} is crucial to generation of phosphotidylinosotol (4, 5) P2. PIP5K1{beta} 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 PIP5K1{beta} in osteoclastogenesis and osteogenesis to provide promising strategies for osteoporosis prevention and treatment. We discovered that PIP5k1{beta} deletion in mice resulted in obvious bone loss and PIP5K1{beta} was highly expressed both during osteoclast and osteoblast differentiation, besides, PIP5K1{beta} deletion enhanced the proliferation and migration of BMMs to promote osteoclast differentiation. PIP5k1{beta}-/- osteoclast exhibited normal cytoskeleton architecture but stronger resorption activity. PIP5k1{beta} 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, PIP5K1{beta} enhanced osteoblast differentiation by upregulating master genes expression through triggering smad1/5/8 signaling. Thereby, PIP5K1{beta} modulate bone homeostasis and remodeling.

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Zhao, X.-y., Hu, G., Wang, C., Jiang, L., Zhao, J., Xu, J., Zhang, X.. 2018-03-26. PIP5k1 β controls bone homeostasis through modulating both osteoclast and osteoblast differentiation. https://doi.org/10.1101/288910

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