Dataset Information

CCR2⁺ Macrophages Promote Orthodontic Tooth Movement and Alveolar Bone Remodeling.

ABSTRACT: During mechanical force-induced alveolar bone remodeling, macrophage-mediated local inflammation plays a critical role. Yet, the detailed heterogeneity of macrophages is still unknown. Single-cell RNA sequencing was used to study the transcriptome heterogeneity of macrophages during alveolar bone remodeling. We identified macrophage subclusters with specific gene expression profiles and functions. CellChat and trajectory analysis revealed a central role of the Ccr2 cluster during development, with the CCL signaling pathway playing a crucial role. We further demonstrated that the Ccr2 cluster modulated bone remodeling associated inflammation through an NF-κB dependent pathway. Blocking CCR2 could significantly reduce the Orthodontic tooth movement (OTM) progression. In addition, we confirmed the variation of CCR2⁺ macrophages in human periodontal tissues. Our findings reveal that mechanical force-induced functional shift of the Ccr2 macrophages cluster mediated by NF-κB pathway, leading to a pro-inflammatory response and bone remodeling. This macrophage cluster may represent a potential target for the manipulation of OTM.

SUBMITTER: Xu H

PROVIDER: S-EPMC8854866 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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CCR2<sup>+</sup> Macrophages Promote Orthodontic Tooth Movement and Alveolar Bone Remodeling.

Xu Hao H Zhang Shuting S Sathe Adwait Amod AA Jin Zhichun Z Guan Jiani J Sun Wen W Xing Chao C Zhang Hanwen H Yan Bin B

Frontiers in immunology 20220204

During mechanical force-induced alveolar bone remodeling, macrophage-mediated local inflammation plays a critical role. Yet, the detailed heterogeneity of macrophages is still unknown. Single-cell RNA sequencing was used to study the transcriptome heterogeneity of macrophages during alveolar bone remodeling. We identified macrophage subclusters with specific gene expression profiles and functions. CellChat and trajectory analysis revealed a central role of the <i>Ccr2</i> cluster during developm ...[more]

PMID: 35185928

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Project description:BackgroundYes-associated protein (YAP) is a crucial mechanosensor involved in mechanotransduction, but its role in regulating mechanical force-induced bone remodeling during orthodontic tooth movement (OTM) is unclear. This study aims to elucidate the relationship between mechanotransduction and mechanical force-induced alveolar bone remodeling during OTM.ResultsOur study confirms an asynchronous (temporal and spatial sequence) remodeling pattern of the alveolar bone under mechanical force during OTM. Both compression and tension activate osteoclasts recruiting to the alveolar bone, whereas no significant presence of osteoblasts in the alveolar bone at the early stages of bone remodeling. Specifically, applying different force magnitudes (10, 25, 50, 100 g) to rats' 1st molars affected OTM distance. Force-induced alveolar bone remodeling was characterized by osteoclastogenesis and YAP activation at compressive/tensile sites on day 1 of OTM. Notably, 25 g force triggered peak YAP expression and osteoclastic activity early on. Time-course analysis revealed two YAP activity peaks on day1 and 14, contrasting with one peak of type I collagen expression on day14. In addition, RNA-sequencing highlighted increased nuclear factor kappa B (NF-κB) signaling, mineral absorption, and osteoclast differentiation at day-1 and 3. Moreover, gene expression analysis showed similar trends for NF-κB p65, YAP1, and TEA domain 1 (TEAD1) during this time. Furthermore, experiments on osteoclast cultures indicated YAP activation via large tumor suppressor (LATS) and TEAD under mechanical stimuli (compression/tension), promoting osteoclastogenesis by regulating NF-κB p65 and receptor activator of NF-κB (RANK). Inhibiting YAP with verteporfin delayed OTM by impairing force-induced osteoclastic activities in vivo and ex-vivo.ConclusionsWe propose that YAP mediates alveolar bone remodeling through NF-κB p65-induced osteoclastogenesis in an asynchronous remodeling pattern during OTM. Both compression and tension activate osteoclasts recruiting to the alveolar bone at early stages of bone remodeling, offering evidence for orthodontists as a reference.

Dataset Information

CCR2⁺ Macrophages Promote Orthodontic Tooth Movement and Alveolar Bone Remodeling.

Publications

CCR2<sup>+</sup> Macrophages Promote Orthodontic Tooth Movement and Alveolar Bone Remodeling.

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Dataset Information

CCR2+ Macrophages Promote Orthodontic Tooth Movement and Alveolar Bone Remodeling.

Publications

CCR2<sup>+</sup> Macrophages Promote Orthodontic Tooth Movement and Alveolar Bone Remodeling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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CCR2⁺ Macrophages Promote Orthodontic Tooth Movement and Alveolar Bone Remodeling.