Department of Prosthodontics and Implantology, School and Hospital of Stomatology of Guizhou Medical University, Guiyang, Guizhou, China.
Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology of Guizhou Medical University, Guiyang, China.
Front Immunol. 2023 Apr 20;14:1121549. doi: 10.3389/fimmu.2023.1121549. eCollection 2023.
Bone defect repair by implanting bone substitute materials has been a common clinical treatment. With the understanding of substance-immune system interactions and increasing evidence indicating that the post-implantation immune response determines the fate of bone substitute materials, active modulation of host macrophage polarization is considered a promising strategy. However, whether the same regulatory effects exist when an individual immune system is altered with aging is unclear.
In this study, we mechanistically investigated the effect of immunosenescence on the active regulation of macrophage polarization by establishing a cranial bone defect model in young and aged rats implanted with Bio-Oss®. Forty-eight young and 48 aged specific pathogen-free (SPF) male SD rats were randomly divided into two groups. In the experimental group, 20 μL of IL-4 (0.5 μg/mL) was injected locally on the third to seventh postoperative days, while an equal volume of PBS was injected in the control group. Specimens were collected at 1, 2, 6, and 12 weeks postoperatively, and bone regeneration at the defect site was evaluated by micro-CT, histomorphometry, immunohistochemistry, double-labeling immunofluorescence, and RT-qPCR.
The application of exogenous IL-4 reduced activation of NLRP3 inflammasomes by promoting the polarization of M1 macrophages to M2 macrophages, thus promoting bone regeneration at the site of bone defects in aged rats. However, this effect was gradually weakened after the IL-4 intervention was discontinued.
Our data confirmed that a strategy to regulate macrophage polarization is also feasible under conditions of immunosenescence, i.e., the local inflammatory microenvironment can be regulated by reducing M1-type macrophages. However, further experiments are needed to determine an exogenous IL-4 intervention that can maintain a more sustained effect.
植入骨替代材料修复骨缺损一直是一种常见的临床治疗方法。随着人们对物质-免疫系统相互作用的认识不断深入，越来越多的证据表明，植入后免疫反应决定了骨替代材料的命运，因此主动调节宿主巨噬细胞极化被认为是一种很有前途的策略。然而，当个体免疫系统随着衰老而改变时，这种调节是否存在相同的效果尚不清楚。
在这项研究中，我们通过建立年轻和衰老大鼠颅骨骨缺损模型，并植入 Bio-Oss®，从机制上研究了免疫衰老对巨噬细胞极化主动调节的影响。将 48 只年轻和 48 只衰老的特定病原体（SPF）雄性 SD 大鼠随机分为两组。实验组在术后第 3 至第 7 天局部注射 20 μL 的 IL-4（0.5 μg/mL），对照组注射等量的 PBS。术后 1、2、6 和 12 周采集标本，通过 micro-CT、组织形态计量学、免疫组织化学、双标记免疫荧光和 RT-qPCR 评估缺损部位的骨再生情况。
外源性 IL-4 的应用通过促进 M1 巨噬细胞向 M2 巨噬细胞极化来减少 NLRP3 炎性小体的激活，从而促进了老年大鼠骨缺损部位的骨再生。然而，这种效应在停止 IL-4 干预后逐渐减弱。
我们的数据证实，调节巨噬细胞极化的策略在免疫衰老的情况下也是可行的，即可以通过减少 M1 型巨噬细胞来调节局部炎症微环境。然而，需要进一步的实验来确定一种外源性 IL-4 干预方法，以维持更持续的效果。
