image: PC1, as a mechanical stress sensitive factor, influences osteoclastogenesis and bone resorption by regulating TAZ nuclear translocation. Patients with ADPKD, which is mainly caused by loss-of-function mutation of the PKD1 gene, have lower risk of hip fracture than those with other chronic kidney diseases
Credit: ©Science China Press
Recently, professor Changjun Li and his colleagues in Xiangya Hospital of Central South University has published a research paper in Science Bulletin. In the paper, the authors pointed out that mechanical loading is required for bone homeostasis, but the underlying mechanism is still unclear. Their research found that mechanosensitive protein polycystin-1 (PC1, encoded by Pkd1) played an important role in osteoclast-mediated bone resorption. The authors conducted a cohort study of 32,500 patients and found that patients with autosomal dominant polycystic kidney disease, which is mainly caused by loss-of-function mutation of the PKD1 gene, had significantly lower risk of hip fracture than those with other chronic kidney diseases. Furthermore, the conditional deletion of Pkd1 in the osteoclast lineage resulted in decreased bone resorption, increased bone mass and complete resistance to unloading-induced bone loss. A mechanistic study revealed that PC1 facilitated TAZ nuclear translocation via the C-terminal domain, thereby increasing the transcription of osteoclast-related genes, and that conditional deletion of Taz in the osteoclast lineage resulted in reduced osteoclastogenesis and increased bone mass. Pharmacological regulation of the PC1-TAZ axis alleviated unloading- and estrogen deficiency- induced bone loss. The research team elucidated a new mechanism by which mechanical loading could directly regulate bone resorption and affect bone homeostasis, which provided a potential new therapeutic target for the prevention and treatment of osteoclast-related osteoporosis. Mei Huang, an assistant researcher in Xiangya Hospital of Central South University, is the first author of the paper. Prof. Changjun Li, Prof. Guanghua Lei, Prof. Xianghang Luo and Prof. Chao Zeng are co-corresponding authors.
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See the article:
Mechanical Protein Polycystin-1 Directly Regulates Osteoclastogenesis and Bone Resorption
https://doi.org/10.1016/j.scib.2024.04.044
Journal
Science Bulletin