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 (β-TCP) is a synthetic ceramic biomaterial that has shown promise as bone substitute. However, whether and how β-TCP affects osteogenesis-related responses of macrophages has rarely been studied. The aims of this study were to explore (a) the effects of β-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 β-TCP-induced co-cultured BMSCs compared to that in BMSC monocultures. We also found that macrophages induced with 25 mg ml−1 β-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 β-TCP extract. Our findings suggest that β-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.

3D-Printed β-Tricalcium Phosphate Scaffolds Promote Osteogenic Differentiation of Bone Marrow-Deprived Mesenchymal Stem Cells in an N6-methyladenosineDependent Manner

“…The concentrations of Ca and P ions (Ctrl, 1/32, 1/64, and 1/128) were detected by ICP-AES, as shown in Figure 1A . The concentrations of Ca were 66.20 ± 1.53, 65.37 ± 0.81, 64.26 ± 0.97, and 65.79 ± 1.26 mg/L in Ctrl, 1/32, 1/64, and 1/128 dilutions, respectively, while the concentrations of P were 32.05 ± 1.64, 29.96 ± 0.65, 29.80 ± 0.96, and 30.99 ± 0.19 mg/L, respectively, which were consistent with a previous study and showed no significant difference in the concentrations of Ca and P[ 27 ]. The pH values were 7.353 ± 0.012, 7.343 ± 0.012, 7.427 ± 0.009, and 7.427 ± 0.021, respectively ( Figure 1B ).…”

“…Therefore, these two elements of β-TCP promote bone regeneration. Herein, we detected the release of calcium and phosphorus, which was also reported in a previous study[ 27 ]. No significant difference existing among the four groups was possibly linked to the precipitation of calcium phosphate.…”

A Novel Immunoregulatory PEGylated Poly(glycerol sebacate)/β‐TCP Membrane for Application in Guided Bone Regeneration

“…Moreover, β‐TCP further enhanced PEGS membrane‐induced M2 polarization, which resulted in significant M2 macrophage infiltration in defects treated with the PEGS/β‐TCP membrane at earlier stages. This finding was supported by the study of Zheng et al., [ 26 ] which demonstrated that β‐TCP extract upregulates M2 polarization by regulating the Wnt signaling pathway. Following the increase in M2 macrophages, the PEGS/β‐TCP membrane induced higher expression of VEGF, IGF‐1, BMP2, and TGF‐β1 than did the PEGS membrane.…”

The crosstalk between macrophages and bone marrow mesenchymal stem cells in bone healing

“…In another study, scientists transplanted TCP particles loaded with histone methyltransferase enhancer of zeste1 (EZH1) into animal models and they found that the proportion of M 2 Mϕs was significantly increased compared with that of in the control group [ 44 ]. Moreover, another study recently has shown that β-TCP particles had the ability to enhance the osteogenic differentiation of BMSCs by inducing the polarization of Mϕs and regulating the Wnt signaling pathway [ 185 ]. However, the function of TCP particles on bone immune system is still in dispute.…”