Calcium silicate bioactive ceramics induce osteogenesis through oncostatin M

Abstract

Immune reactions are a key factor in determining the destiny of bone substitute materials after implantation. Macrophages, the most vital factor in the immune response affecting implants, are critical in bone formation, as well as bone biomaterial-mediated bone repair. Therefore, it is critical to design materials with osteoimmunomodulatory properties to reduce host-to-material inflammatory responses by inducing macrophage polarization. Our previous study showed that calcium silicate (CS) bioceramics could significantly promote osteogenesis. Herein, we further investigated the effects of CS on the behavior of macrophages and how macrophages regulated osteogenesis. Under CS extract stimulation, the macrophage phenotype was converted to the M2 extreme. Stimulation by a macrophage-conditioned medium that was pretreated by CS extracts resulted in a significant enhancement of osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), indicating the important role of macrophage polarization in biomaterial-induced osteogenesis. Mechanistically, oncostatin M (OSM) in the macrophage-conditioned medium promoted osteogenic differentiation of BMSCs through the ERK1/2 and JAK3 pathways. This in vivo study further demonstrated that CS bioceramics could stimulate osteogenesis better than β-TCP implants by accelerating new bone formation at defective sites in the femur. These findings improve our understanding of immune modulation of CS bioactive ceramics and facilitate strategies to improve the in vitro osteogenesis capability of bone substitute materials.