Improved BMP2-CPC-stimulated Osteogenesis in Vitro and in Vivo via Modulation of Macrophage Polarization

Abstract This study aimed to explore the in vitro and in vivo roles of macrophages in the osteogenesis stimulated by BMP2-CPC. In vitro, the alteration of macrophage polarization and cytokine secretion induced by BMP2-CPC or CPC was investigated. The influence of conditioned medium derived from BMP2-CPC- or CPC-stimulated macrophages on the migration and osteogenic differentiation of MSCs were evaluated. The in vivo relationship between macrophage polarization and osteogenesis was examined in a rabbit calvarial defect model. The in vitro results indicated that BMP2-CPC and CPC induced different patterns of macrophage polarization and subsequently resulted in distinct patterns of cytokine expression and secretion. Conditioned medium derived from BMP2-CPC- or CPC-stimulated macrophages both exhibited apparent osteogenic effect on MSCs. Notably, BMP2-CPC induced more M2-phenotype polarization and higher expression of anti-inflammatory cytokines and growth factors than did CPC, which led to the better osteogenic effect of conditioned medium derived from BMP2-CPC-stimulated macrophages. The rabbit calvarial defect model further confirmed that BMP2-CPC facilitated more bone regeneration than CPC did by enhancing M2-phenotype polarization in local macrophages and then alleviating inflammatory reaction. In conclusion, this study revealed that the favorable immunoregulatory property of BMP2-CPC contributed to the strong osteogenic capability of BMP2-CPC by modulating macrophage polarization.