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.

骨质疏松症是一种溶骨性疾病，通常与过度的破骨细胞形成有关。具有 PDZ 结合基序 (TAZ) 的转录共激活因子是 Hippo 信号通路的关键下游效应子；建议参与骨稳态的调节。然而，TAZ 在破骨细胞中的确切作用尚未确定。在这项研究中，我们证明了 TAZ 的整体敲除和破骨细胞特异性敲除导致破骨细胞形成增加导致低骨量表型，体外破骨细胞形成试验进一步证明了这一点。此外，TAZ 的过表达抑制了 RANKL 诱导的破骨细胞形成，而 TAZ 的沉默减少了它。从机制上讲，TAZ 与 TGF 活化激酶 1 (TAK1) 结合并相互抑制 NF-κB 信号传导，抑制破骨细胞分化。