Department of Orthodontics, Shanghai 9th Peoples Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, People's Republic of China.
Department of Pediatric Dentistry, Shanghai 9th Peoples Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 639 Zhizaoju Road, Shanghai, People's Republic of China.
Biomed Mater. 2021 Feb 18;16(2):025005. doi: 10.1088/1748-605X/abdbdc.
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 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.
巨噬细胞是骨骼重塑和骨修复的重要调节者。β-磷酸三钙（β-TCP）是一种合成陶瓷生物材料，已显示出作为骨替代物的潜力。然而，β-TCP 是否以及如何影响巨噬细胞的成骨相关反应很少被研究。本研究的目的是探讨（a）β-TCP 对与巨噬细胞共培养的骨髓间充质干细胞（BMSCs）成骨分化的影响，以及（b）β-TCP 对巨噬细胞极化以及巨噬细胞基因和蛋白表达谱的影响。与 BMSC 单核培养相比，β-TCP 诱导的共培养 BMSC 体外成骨分化能力增强。我们还发现，用 25mg/mlβ-TCP 提取物诱导的巨噬细胞具有更显著的免疫反应，并向 M2 表型转变。用β-TCP 提取物处理的巨噬细胞中 Wnt 信号通路调节剂 Wnt 信号通路调节剂无翅型 MMV 整合位点家族成员 6（WNT6）和 Wnt 抑制因子 1（WIF1）的表达水平分别上调和下调。我们的研究结果表明，β-TCP 通过诱导巨噬细胞极化和调节 Wnt 信号通路来增强 BMSCs 的成骨分化，从而突出了其通过骨免疫调节特性促进骨愈合的治疗潜力。
