Abstract: Objective:?To investigate the role of macrophage major vault protein (MVP) on bone regeneration. Methods:? Macrophage-specific MVP knockout (CKO) and wild-type (WT) C57BL/6 mice were used to establish a tibial mono-cortical defect model, and the bone regeneration was observed by Micro-CT and hematoxylin-eosin (H&E) staining. Macrophages from WT or CKO mice bone marrow were co-cultured with wild-type bone marrow mesenchymal stem cell (BMSC), respectively. The effect of macrophage MVP on BMSC osteogenic differentiation was tested by alkaline phosphatase (ALP) staining and qRT-PCR. Finally, a cytokine array was used to test the cytokine profile of macrophages to understand the regulation of MVP on cytokines secretion. Results:?On day 14 of bone defect, Micro-CT scan and reconstruction results showed that the mineralized tissue in the defect area of CKO mice was less than that of WT mice (P＜0.05); hematoxylin-eosin staining results showed that the bone area in the defect area of CKO mice was less than that of WT mice; In the in vitro co-culture assay, the levels of osteogenic differentiation marker genes were significantly lower in BMSC co-cultured with CKO macrophages than in those co-cultured with WT macrophages (P＜0.05). Cytokine array results showed that macrophages lacking MVP secreted more cytokines including CCL2, CCL4, CXCL10, CCL3, IL-7 that inhibit osteogenic differentiation. Conclusions:?Macrophage MVP may regulate bone regeneration by promoting BMSC osteogenic differentiation.

Key words: major vault protein, macrophage, bone regeneration, osteogenic differentiation, cytokine