TAZ inhibits osteoclastogenesis by attenuating TAK1/NF-κB signaling

摘要

Osteoporosis is an osteolytic disorder commonly associated with excessive osteoclast formation.Transcriptional coactivator with PDZ-binding motif(TAZ)is a key downstream effector of the Hippo signaling pathway;it was suggested to be involved in the regulation of bone homeostasis.However,the exact role of TAZ in osteoclasts has not yet been established.In this study,we demonstrated that global knockout and osteoclast-specific knockout of TAZ led to a low-bone mass phenotype due to elevated osteoclast formation,which was further evidenced by in vitro osteoclast formation assays.Moreover,the overexpression of TAZ inhibited RANKL-induced osteoclast formation,whereas silencing of TAZ reduced it.Mechanistically,TAZ bound to TGF-activated kinase 1(TAK1)and reciprocally inhibited NF-κB signaling,suppressing osteoclast differentiation.Collectively,our findings highlight an essential role of TAZ in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism.