CCR2+ Macrophages Promote Orthodontic Tooth Movement and Alveolar Bone Remodeling

Xu, Hao; Zhang, Shuting; Sathe, Adwait Amod; Jin, Zhichun; Guan, Jiani; Sun, Wen; Xing, Chao; Zhang, Hanwen; Yan, Bin

doi:10.3389/fimmu.2022.835986

Cited by 11 publications

(5 citation statements)

References 37 publications

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“…Thus, we assume that the synchronous up-regulation of M1 and M2 could be the result of this macrophage heterogeneity in the late stage of the immune response induced by compression. This hypothesis is supported indirectly by single-cell sequencing results [ 31 ]. Furthermore, iNOS was the first marker to respond to mechanical stimulation, and did so earlier than Arg1 and IL-10.…”

Section: Discussionmentioning

confidence: 82%

Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation

Wang

Groeger

Yong

et al. 2023

IJMS

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Orthodontic tooth movement is a complex periodontal remodeling process triggered by compression that involves sterile inflammation and immune responses. Macrophages are mechanically sensitive immune cells, but their role in orthodontic tooth movement is unclear. Here, we hypothesize that orthodontic force can activate macrophages, and their activation may be associated with orthodontic root resorption. After force-loading and/or adiponectin application, the migration function of macrophages was tested via scratch assay, and Nos2, Il1b, Arg1, Il10, ApoE, and Saa3 expression levels were detected using qRT-PCR. Furthermore, H3 histone acetylation was measured using an acetylation detection kit. The specific inhibitor of H3 histone, I-BET762, was deployed to observe its effect on macrophages. In addition, cementoblasts were treated with macrophage-conditioned medium or compression force, and OPG production and cellular migration were measured. We further detected Piezo1 expression in cementoblasts via qRT-PCR and Western-blot, and its effect on the force-induced impairment of cementoblastic functions was also analyzed. Compressive force significantly inhibited macrophage migration. Nos2 was up-regulated 6 h after force-loading. Il1b, Arg1, Il10, Saa3, and ApoE increased after 24 h. Meanwhile, higher H3 histone acetylation was detected in the macrophages subjected to compression, and I-BET762 dampened the expression of M2 polarization markers (Arg1 and Il10). Lastly, even though the activated macrophage-conditioned medium showed no effect on cementoblasts, compressive force directly impaired cementoblastic function by enhancing mechanoreceptor Piezo1. Compressive force activates macrophages; specifically, it causes M2 polarization via H3 histone acetylation in the late stage. Compression-induced orthodontic root resorption is macrophage-independent, but it involves the activation of mechanoreceptor Piezo1.

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Section: Discussionmentioning

confidence: 82%

Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation

Wang

Groeger

Yong

et al. 2023

IJMS

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“…Also, trajectory analysis of single-cell RNA sequencing data further demonstrated that the proliferative differentiation of macrophages originated from the MHC-II clusters and expressed more genes for antigen processing and presentation [ 57 ]. In the present work, we recognized the MS4A6A gene as the final potential biomarker of the disease development after rigorous filtration and validation by external datasets.…”

Section: Discussionmentioning

confidence: 99%

Identifying MS4A6A+ macrophages as potential contributors to the pathogenesis of nonalcoholic fatty liver disease, periodontitis, and type 2 diabetes mellitus

Wu,

Wang,

Duan

et al. 2024

Heliyon

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“…Specifically, in the present study, the O + B group showed significant increases in four parameters, i.e., the trabecular bone volume, bone marrow volume, bone volume fraction, and trabecular thickness, indicating more bone formation in this group during OTM with BG material augmentation. This might have been caused by the recruitment of osteoclasts and inflammatory cells early in the remodeling process under mechanical force, leading to enhanced osteoclast-mediated bone resorption followed by osteoblast-mediated bone formation [6,28,29]. The process might accelerate the remodeling of the alveolar bone with bovine bone mineral grafts under mechanical force, resulting in more newly-formed bone tissues in the O + B group.…”

Section: Discussionmentioning

confidence: 99%

Mechanical force increases tooth movement and promotes remodeling of alveolar bone defects augmented with bovine bone mineral

Deng,

Zhuang,

et al. 2024

Prog Orthod.

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Background Orthodontic tooth movement (OTM) in a region containing alveolar bone defects with insufficient height and width is hard to achieve. Bovine bone mineral (Bio-Oss) is available to restore the alveolar defect; however, whether the region augmented with a bovine bone mineral graft (BG) is feasible for OTM, and the mechanisms by which macrophages remodel the BG material, is uncertain under the mechanical force induced by OTM. Material and methods Rats were divided into three groups: OTM (O), OTM + BG material (O + B), and Control (C). First molars were extracted to create bone defects in the O and O + B groups with bovine bone mineral grafting in the latter. Second molars received OTM towards the bone defects in both groups. After 28 days, maxillae were analyzed using microfocus-computed tomography (μCT) and scanning-electron-microscopy (SEM); and macrophages (M1/M2) were stained using immunofluorescence. THP-1 cell-induced macrophages were cultured under mechanical force (F), BG material (B), or both (F + B). Phagocytosis-related signaling molecules (cAMP/PKA/RAC1) were analyzed, and conditioned media was analyzed for MMP-9 and cytokines (IL-1β, IL-4). Results Our study demonstrated that alveolar defects grafted with BG materials are feasible for OTM, with significantly increased OTM distance, bone volume, and trabecular thickness in this region. SEM observation revealed that the grafts served as a scaffold for cells to migrate and remodel the BG materials in the defect during OTM. Moreover, the population of M2 macrophages increased markedly both in vivo and in cell culture, with enhanced phagocytosis via the cAMP/PKA/RAC1 pathway in response to mechanical force in combination with BG particles. By contrast, M1 macrophage populations were decreased under the same circumstances. In addition, M2 macrophage polarization was also indicated by elevated IL-4 levels, reduced IL-1β levels, and less active MMP-9 in cell culture. Conclusion This study explored the mechanisms of mechanical force-induced alveolar bone remodeling with bovine bone mineral grafts during OTM. The results might provide molecular insights into the related clinical problems of whether we can move teeth into the grafted materials; and how these materials become biologically remodeled and degraded under mechanical force.

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CCR2+ Macrophages Promote Orthodontic Tooth Movement and Alveolar Bone Remodeling

Cited by 11 publications

References 37 publications

Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation

Orthodontic Compression Enhances Macrophage M2 Polarization via Histone H3 Hyperacetylation

Identifying MS4A6A+ macrophages as potential contributors to the pathogenesis of nonalcoholic fatty liver disease, periodontitis, and type 2 diabetes mellitus

Mechanical force increases tooth movement and promotes remodeling of alveolar bone defects augmented with bovine bone mineral

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