Osteocytes Produces RANKL Via Wnt-TGFβ Signaling Axis for Osteoclastogenesis
Yujiao Liu, Lizhou Zhao, Molin Li, Weimin Gong, Xiaofang Wang, Yu Cheng, Ying Zhang, Pengtao Wang, Yisheng Luo, Yining Zhang, Yufei Shao, Makoto M. Taketo, Teresita Bellido, Gaohai Shao, Xing Liu, Xiaolin Tu
Abstract
data highlight the specificity of osteocytic Wnt, rather than osteoblastic Wnt, in regulating TGFβ signaling. Activation/inactivation of osteocytic TGFβ signaling stringently promotes/inhibits RANKL expression and osteoclast differentiation in dose- and time-dependent manners. Wnt signaling increases RANKL expression through TGFβ signaling via the physical interaction of its transcription factor Smad4 with the RANKL promoter region. Mice with disrupted TGFβ signaling in osteocytes recapitulate defective osteoclastogenesis and reduced RANKL expression in osteocytes. Thus, osteocytes mediate bone resorption via Wnt-TGFβ signaling axis.