Mechanical protein polycystin-1 directly regulates osteoclastogenesis and bone resorption

• DOI: 10.1016/j.scib.2024.04.044
• Publication Date: 2024-04-23T01:45:44Z
• Authors: Mei Huang; Jingxuan Zhou; Xiaoxiao Li; Ran Liu; Yangzi Jiang; Kaixuan Chen; Yurui Jiao; Xin Yin; Ling Liu; Yuchen Sun; Weishan Wang; Ye Xiao; Tian Su; Qi Guo; Yan Huang; Mi Yang; Jie Wei; L. Darryl Quarles; Zhousheng Xiao; Chao Zeng; Xianghang Luo; Guanghua Lei; Changjun Li
• Keywords: Conditional gene knockout; Bone remodeling; PKD1

Mechanical loading is required for bone homeostasis, but the underlying mechanism still unclear. Our previous studies revealed that mechanical protein polycystin-1 (PC1, encoded by Pkd1) critical formation. However, role of PC1 in resorption unknown. Here, we found directly regulates osteoclastogenesis and resorption. The conditional deletion Pkd1 osteoclast lineage resulted a reduced number osteoclasts, decreased resorption, increased mass. A cohort study 32,500 patients further autosomal dominant polycystic kidney disease, which mainly caused loss-of-function mutation PKD1 gene, associated with lower risk hip fracture than those other chronic diseases. Moreover, mice osteoclast-specific knockout showed complete resistance to unloading-induced loss. mechanistic facilitated TAZ nuclear translocation via C-terminal tail-TAZ complex Taz Pharmacological regulation PC1-TAZ axis alleviated unloading- estrogen deficiency- induced Thus, may be potential therapeutic target osteoclast-related osteoporosis.