The Important Role of Polycystin in the Skeletal System

The polycystin (PC) protein family, including Polycystin-1 (PC1) and Polycystin-2 (PC2), was initially identified for its role in autosomal dominant polycystic kidney disease (ADPKD). Recent studies reveal that these mechanosensitive proteins play significant roles in skeletal development, homeostasis, and disease. PC1 and PC2 participate in mechanotransduction in bone cells and regulate the differentiation and function of osteoblasts, osteoclasts, and other skeletal cells through multiple signaling pathways, thereby influencing bone remodeling. Dysregulation of PC signaling is associated with various skeletal disorders, including osteoporosis, impaired fracture healing, craniosynostosis, and maxillofacial abnormalities. This review summarizes the structure, expression, molecular mechanisms, and clinical significance of polycystins in the skeletal system. We discuss their roles in different bone cell types, the signaling pathways involved, and emerging therapeutic strategies targeting PC-mediated mechanotransduction. Understanding the mechanosensitive functions of polycystins in bone provides a theoretical basis for developing new approaches to prevent and treat skeletal diseases. Further research on mechanisms and therapeutic applications will help elucidate bone metabolism regulation and advance clinical management of related conditions.