School of Dentistry of Bauru, University of São Paulo (FOB/USP), Bauru, SP, Brazil.
School of Dentistry of Bauru, University of São Paulo (FOB/USP), Bauru, SP, Brazil; Department of Bioengineering, The University of Texas at Dallas, Richardson, TX, United States of America.
Bone. 2022 Oct;163:116506. doi: 10.1016/j.bone.2022.116506. Epub 2022 Jul 25.
The alveolar bone repair process may be influenced by multiple local and systemic factors, which include immune system cells and mediators. Macrophages allegedly play important roles in the repair process, and the transition of an initial inflammatory M1 profile into a pro-reparative M2 profile theoretically contributes to a favorable repair outcome. In this context, considering immunoregulatory molecules as potential targets for improving bone repair, this study evaluated the role of the immunoregulatory molecule FTY720, previously described to favor the development of the M2 phenotype, in the process of alveolar bone healing in C57Bl/6 (WT) mice. Experimental groups submitted to tooth extraction and maintained under control conditions or treated with FTY720 were evaluated by microtomographic (μCT), histomorphometric, immunohistochemical and molecular analysis to characterize healing and host response features at 0, 1, 3, 7 and 14 days. Our results demonstrated that the FTY720 group presented higher bone tissue density, higher bone tissue volume, greater tissue volume fraction, greater number and thickness of trabeculae and a higher number of osteoblasts and osteoclasts than the control group. Accordingly, the bone markers BMP2, BMP7, ALPL, SOST and RANK mRNA expressions increased in the FTY720 treated group. Furthermore, the levels of FIZZ, ARG2 and IL-10 mRNA increased in the FTY720 group together with the presence of CD206 cells, suggesting that the boost of bone formation mediated by FTY720 involves an increased polarization and activity of M2 macrophages in healing sites. Thus, our results demonstrate that FTY720 favored the process of alveolar bone repair, probably trough a strengthened M2 response, associated with an increased expression of markers osteogenic differentiation and activity markers. Immunoregulatory strategies based in the modulation of macrophage polarization profile can comprise effective tools to improve the bone repair process.
牙槽骨修复过程可能受到多种局部和全身因素的影响，包括免疫系统细胞和介质。巨噬细胞据称在修复过程中发挥重要作用，初始炎症性 M1 表型向促修复的 M2 表型的转变理论上有助于产生有利的修复结果。在这种情况下，考虑到免疫调节分子是改善骨修复的潜在靶点，本研究评估了免疫调节分子 FTY720 的作用，先前的研究表明 FTY720 有利于 M2 表型的发展，在 C57Bl/6（WT）小鼠的牙槽骨愈合过程中。通过 microtomographic（μCT）、组织形态计量学、免疫组织化学和分子分析评估实验组接受拔牙并在对照条件下或用 FTY720 治疗的情况，以在 0、1、3、7 和 14 天评估愈合和宿主反应特征。我们的结果表明，FTY720 组的骨组织密度、骨组织体积、组织体积分数、小梁数量和厚度以及成骨细胞和破骨细胞数量均高于对照组。相应地，骨标志物 BMP2、BMP7、ALPL、SOST 和 RANK mRNA 的表达在 FTY720 处理组中增加。此外，FTY720 组的 FIZZ、ARG2 和 IL-10 mRNA 水平增加，同时出现 CD206 细胞，表明 FTY720 介导的骨形成增强涉及愈合部位 M2 巨噬细胞的极化和活性增强。因此，我们的结果表明，FTY720 有利于牙槽骨修复过程，可能是通过增强 M2 反应，同时增加成骨分化标志物和活性标志物的表达。基于巨噬细胞极化谱调节的免疫调节策略可能是改善骨修复过程的有效工具。
