Beta-tricalcium phosphate promotes osteogenic differentiation of bone marrow-derived mesenchymal stem cells through macrophages.

ABSTRACT

Macrophages are vital regulators of skeletal remodeling and osseous repair. Beta-tricalcium phosphate (ß-TCP) is a synthetic ceramic biomaterial that has shown promise as bone substitute. However, whether and how ß-TCP affects osteogenesis-related responses of macrophages has rarely been studied. The aims of this study were to explore (a) the effects of ß-TCP on osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) co-cultured with macrophages and (b) on macrophage polarization as well as macrophage gene and protein expression profiles. BMSC osteogenic differentiation capacity in vitro was enhanced in ß-TCP-induced co-cultured BMSCs compared to that in BMSC monocultures. We also found that macrophages induced with 25 mg ml-1 ß-TCP extract had more significant immune responses and switched to the M2 phenotype. Expression levels of the Wnt signaling pathway modulators wingless-type MMTV integration site family, member 6 (WNT6) and Wnt inhibitory factor 1 (WIF1) were upregulated and downregulated, respectively, in macrophages treated with ß-TCP extract. Our findings suggest that ß-TCP enhances osteogenic differentiation of BMSCs by inducing macrophage polarization and by regulating the Wnt signaling pathway, thereby highlighting its therapeutic potential for bone healing through osteoimmunomodulatory properties.