MVP, also known as major vault protein, is a crucial protein involved in various biological processes, especially those related to macrophages and bone homeostasis. In macrophages, it is associated with the JAK2-STAT6 pathway [1]. In bone, it is related to osteoclastogenesis and the calcineurin-NFATc1 pathway [2]. It also has a significant impact on bone remodeling and immune-related processes in the body. Genetic models, such as KO and CKO mouse models, have been instrumental in studying its functions.

In macrophage-related studies, myeloid-specific MVP gene knockout (MacKO) mice showed impaired fracture repair due to macrophages' inability to transition from a pro-inflammatory to an anti-inflammatory phenotype. This led to enhanced osteoclastic differentiation and impaired osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) [1].

In bone-related investigations, total body (Mvp-/ -) and monocyte-specific (Mvpf/fLyz2-Cre) MVP gene knockout mice exhibited osteoporosis-like phenotypes. MVP-deficiency enhanced calcineurin-NFATc1 signaling, promoting osteoclastogenesis and bone resorption [2]. Also, conditional knockout of MVP in monocyte lineage (Mvpf/fLyz2-Cre mice) inhibited osteoclast apoptosis in osteoporosis contexts of aging and estrogen deficiency [3].

In conclusion, MVP plays essential roles in macrophage-mediated inflammation during fracture repair and in regulating osteoclastogenesis and osteoclast apoptosis, thereby influencing bone homeostasis. The use of MVP KO/CKO mouse models has significantly contributed to understanding its functions in these disease-relevant biological processes, which may provide potential therapeutic targets for fracture treatment and osteoporosis [1,2,3].