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.

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Heterogeneity of fibroblasts directly affects the outcome of tissue regeneration; however, whether bioactive ceramics regulate bone regeneration through fibroblasts is unclear. Ectopic bone formation model with biphasic calcium phosphate (BCP) implantation was used to investigate the temporal and spatial distribution of fibroblasts around ceramics. The effect of BCP on L929 fibroblasts was evaluated by EdU assay, transwell assay, and qRT-PCR. Further, the effect of its conditioned medium on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was confirmed by ALP staining. SEM and XRD results showed that BCP contained abundant micro- and macro-pores and consisted of hydrogen-apatite (HA) and β-tricalcium phosphate (β-TCP) phases. Subsequently, BCP implanted into mice muscle successfully induced osteoblasts and bone formation. Fibroblasts labelled by vimentin gathered around BCP at 7 days and peaked at 14 days post implantation. In vitro, BCP inhibited proliferation of L929 fibroblast but promoted its migration. Moreover, expression of Col1a1, Bmp2, and Igf1 in L929 treated by BCP increased significantly while expression of Tgfb1 and Acta did not change. ALP staining further showed conditioned media from L929 fibroblasts treated by BCP could enhance osteogenic differentiation of BMSCs. In conclusion, fibroblasts mediate ectopic bone formation of calcium phosphate ceramics.

Due to improvements of quality of life and the demand for aesthetics, more and more people are choosing orthodontic treatments, resulting in a surge in adult orthodontic patients in recent years. However, a large amount of clinical evidence shows that many orthodontic patients have mild periodontitis in the periodontal tissues, which affects the efficacy of the orthodontic treatment or aggravates the periodontal condition. Therefore, it is important to identify the key factors that affect orthodontic treatments in this inflammatory environment. The aim of this study was to investigate the role of macrophages in orthodontic treatments under inflammatory environments. By analyzing the functional groups of macrophages in the orthodontic rat model of periodontitis, we found that macrophages with high expression levels of CD301b could improve the periodontal microenvironment and improve the efficiency of the orthodontic tooth movement. CD301b+ macrophages transplanted into the model can promote osteogenesis around orthodontic moving teeth, improve bone remodeling during orthodontic treatment, and accelerate orthodontic tooth movement. Considered together, these results suggest that CD301b+ macrophages may play an active role in orthodontic treatments in inflammatory environments and may serve as potential regulatory targets.

With improvements in the quality of life and the demand for aesthetics, more and more people are opting for orthodontic treatment, resulting in a surge in adult orthodontic patients in recent years. However, a large body of clinical evidence shows that many orthodontic patients experience periodontal inflammation, which hinders the effect of the treatment or exacerbates the periodontal status. Therefore, determining the key factors that affect orthodontic treatment in an inflammatory environment to improve the efficiency of the treatment is vital. In this study, we focused on the critical role of macrophages during orthodontic treatment in an inflammatory environment. The functional population of macrophages was analyzed in a rat orthodontic model with periodontitis. Macrophages with high expression levels of CD301b improved the periodontal microenvironment and the efficiency of the orthodontic tooth movement. Transplantation of CD301b + macrophages into the model promoted osteogenesis around the orthodontic mobile teeth, improved bone remodeling during the orthodontic process, and accelerated orthodontic tooth movement. These findings indicate that CD301b + macrophages may have a positive effect during orthodontic treatment in an inflammatory environment and could be considered as a potential regulatory target.