YAP promotes osteogenesis and suppresses adipogenic differentiation by regulating β-catenin signaling

Jin Xiu Pan, Lei Xiong, Kai Zhao, Peng Zeng, Bo Wang, Fulei Tang, Dong Sun, Hao Han Guo, Xiao Yang, Shun Cui, Wen Fang Xia, Lin Mei, Wen Cheng Xiong

Research output: Contribution to journalArticlepeer-review

177 Scopus citations

Abstract

YAP (yes-associated protein) is a transcriptional factor that is negatively regulated by Hippo pathway, a conserved pathway for the development and size control of multiple organs. The exact function of YAP in bone homeostasis remains controversial. Here we provide evidence for YAP's function in promoting osteogenesis, suppressing adipogenesis, and thus maintaining bone homeostasis. YAP is selectively expressed in osteoblast (OB)-lineage cells. Conditionally knocking out Yap in the OB lineage in mice reduces cell proliferation and OB differentiation and increases adipocyte formation, resulting in a trabecular bone loss. Mechanistically, YAP interacts with β-catenin and is necessary for maintenance of nuclear β-catenin level and Wnt/β-catenin signaling. Expression of β-catenin in YAP-deficient BMSCs (bone marrow stromal cells) diminishes the osteogenesis deficit. These results thus identify YAP-β-catenin as an important pathway for osteogenesis during adult bone remodeling and uncover a mechanism underlying YAP regulation of bone homeostasis.

Original languageEnglish (US)
Article number18
JournalBone Research
Volume6
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Physiology

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