Major Vault Protein (MVP), the main structural protein of the vault complex, is involved in various biological processes. It has been shown to play a role in apoptosis, prevention of metabolic diseases in macrophages, and is associated with multiple signaling pathways such as JAK2-STAT6, calcineurin-NFATc1, and Fas-mediated apoptosis pathways [1,2,3]. Genetic models like Mvpflox/floxLyz2-Cre (myeloid-specific MVP gene knockout, MacKO) and Mvp-/-(total body MVP gene knockout) mice are crucial for studying its functions.

In macrophages, the lack of MVP impairs their transition from a pro-inflammatory to an anti-inflammatory phenotype during fracture repair. This leads to increased secretion of pro-inflammatory cytokines, promoting osteoclastic differentiation and impairing BMSC osteogenic differentiation, ultimately resulting in impaired fracture repair in MacKO mice [1]. In osteoclasts, MVP-deficient mice (Mvp-/-and Mvpf/fLyz2-Cre) exhibit osteoporosis-like phenotypes, as MVP deficiency enhances calcineurin-NFATc1 signaling, promoting osteoclastogenesis and bone resorption [2]. Also, conditional knockout of MVP in monocyte lineage (Mvpf/fLyz2-Cre mice) inhibits osteoclast apoptosis in aging and estrogen-deficiency-related osteoporosis contexts [3].

In conclusion, MVP has immunomodulatory, anti-osteoclastogenic, and pro-osteoclast apoptosis functions. The gene knockout mouse models have significantly contributed to understanding its roles in fracture repair and osteoporosis, providing potential therapeutic targets for these bone-related diseases [1,2,3].