The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) & Key Laboratory of Oral Biomedicine, Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Institute of Infection and Immunity, Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, PR China.
Int J Oral Sci. 2023 May 17;15(1):19. doi: 10.1038/s41368-023-00225-4.
Periodontal bone regeneration is a major challenge in the treatment of periodontitis. Currently the main obstacle is the difficulty of restoring the regenerative vitality of periodontal osteoblast lineages suppressed by inflammation, via conventional treatment. CD301b macrophages were recently identified as a subpopulation that is characteristic of a regenerative environment, but their role in periodontal bone repair has not been reported. The current study indicates that CD301b macrophages may be a constituent component of periodontal bone repair, and that they are devoted to bone formation in the resolving phase of periodontitis. Transcriptome sequencing suggested that CD301b macrophages could positively regulate osteogenesis-related processes. In vitro, CD301b macrophages could be induced by interleukin 4 (IL-4) unless proinflammatory cytokines such as interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were present. Mechanistically, CD301b macrophages promoted osteoblast differentiation via insulin-like growth factor 1 (IGF-1)/thymoma viral proto-oncogene 1 (Akt)/mammalian target of rapamycin (mTOR) signaling. An osteogenic inducible nano-capsule (OINC) consisting of a gold nanocage loaded with IL-4 as the "core" and mouse neutrophil membrane as the "shell" was designed. When injected into periodontal tissue, OINCs first absorbed proinflammatory cytokines in inflamed periodontal tissue, then released IL-4 controlled by far-red irradiation. These events collectively promoted CD301b macrophage enrichment, which further boosted periodontal bone regeneration. The current study highlights the osteoinductive role of CD301b macrophages, and suggests a CD301b macrophage-targeted induction strategy based on biomimetic nano-capsules for improved therapeutic efficacy, which may also provide a potential therapeutic target and strategy for other inflammatory bone diseases.
牙周骨再生是治疗牙周炎的主要挑战。目前，主要障碍是通过常规治疗难以恢复被炎症抑制的牙周成骨细胞谱系的再生活力。最近发现 CD301b 巨噬细胞是一种具有再生环境特征的亚群，但它们在牙周骨修复中的作用尚未报道。本研究表明 CD301b 巨噬细胞可能是牙周骨修复的组成成分，并且它们专注于牙周炎缓解阶段的骨形成。转录组测序表明 CD301b 巨噬细胞可以正向调节成骨相关过程。在体外，除非存在促炎细胞因子（如白细胞介素 1β（IL-1β）和肿瘤坏死因子α（TNF-α）），否则 CD301b 巨噬细胞可以由白细胞介素 4（IL-4）诱导。在机制上，CD301b 巨噬细胞通过胰岛素样生长因子 1（IGF-1）/胸腺瘤病毒原癌基因 1（Akt）/哺乳动物雷帕霉素靶蛋白（mTOR）信号促进成骨细胞分化。设计了一种由负载白细胞介素 4 的金纳米笼作为“核心”和小鼠中性粒细胞膜作为“壳”的成骨诱导纳米胶囊（OINC）。当注入牙周组织时，OINCs 首先吸收炎症性牙周组织中的促炎细胞因子，然后通过远红光照射控制释放白细胞介素 4。这些事件共同促进了 CD301b 巨噬细胞的富集，从而进一步促进了牙周骨再生。本研究强调了 CD301b 巨噬细胞的成骨作用，并提出了一种基于仿生纳米胶囊的 CD301b 巨噬细胞靶向诱导策略，以提高治疗效果，这也可能为其他炎症性骨病提供潜在的治疗靶点和策略。
