2. Academic Validation
  3. CCR2+ Macrophages Promote Orthodontic Tooth Movement and Alveolar Bone Remodeling

CCR2+ Macrophages Promote Orthodontic Tooth Movement and Alveolar Bone Remodeling

  • Front Immunol. 2022 Feb 4;13:835986. doi: 10.3389/fimmu.2022.835986.
Hao Xu 1 2 3,  Shuting Zhang 1 2 4,  Adwait Amod Sathe 5,  Zhichun Jin 1 2 3,  Jiani Guan 1 2 3,  Wen Sun 2,  Chao Xing 5 6 7,  Hanwen Zhang 8 9,  Bin Yan 1 2 3
Affiliations

Affiliations

  • 1 Department of Orthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, China.
  • 2 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
  • 3 Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, China.
  • 4 School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China.
  • 5 Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, United States.
  • 6 Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, United States.
  • 7 Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States.
  • 8 School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
  • 9 Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China.
PMID: 35185928 DOI: 10.3389/fimmu.2022.835986
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.

Keywords

CCR2; bone remodeling; inflammatory; macrophage; single-cell sequencing.

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