TAZ inhibits osteoclastogenesis by attenuating TAK1/NF-κB signaling
Wanlei Yang,
Xuanyuan Lu,
Tan Zhang,
Weiqi Han,
Jianlei Li,
Wei He,
Yewei Jia,
Kangxian Zhao,
An Qin,
Yu Qian
Affiliations
Wanlei Yang
Department of Orthopaedics, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine)
Xuanyuan Lu
Department of Orthopaedics, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine)
Tan Zhang
Department of Orthopaedics, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine)
Weiqi Han
Department of Orthopaedics, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine)
Jianlei Li
Department of Orthopaedics, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine)
Wei He
Department of Orthopaedics, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine)
Yewei Jia
Department of Orthopaedics, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine)
Kangxian Zhao
Department of Orthopaedics, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine)
An Qin
Department of Orthopedic Surgery, Shanghai Key Laboratory of Orthopedic Implants, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine
Yu Qian
Department of Orthopaedics, Shaoxing People’s Hospital (Shaoxing Hospital, Zhejiang University School of Medicine)
Abstract 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.
