The Role of R-Spondins and Their Receptors in Bone Metabolism

The document from 2016 explores the impact of R-spondins (Rspos) and their receptors on bone metabolism, emphasizing their role in the Wnt/ß-catenin signaling pathway which is crucial for bone development and remodeling. Rspos, particularly Rspo1 and Rspo2, are shown to promote osteoblastic differentiation and bone formation, with potential therapeutic implications for bone loss-related diseases. The receptors Lgr4/5/6 and E3 ubiquitin ligases Znrf3/Rnf43 are essential for Rspos' regulatory effects on the skeleton. Studies have demonstrated that Rspo2 is important for bone development and limb elongation, while Rspo1 enhances osteoblastic maturation and mineralization. Additionally, systemic administration of recombinant R-spondin has been found to increase bone mineral apposition rate and bone volume in mouse models. However, the precise molecular mechanisms and signaling pathways of Rspos and their receptors in bone metabolism are not fully understood, necessitating further research.