PMID- 35029749
OWN - NLM
STAT- MEDLINE
DCOM- 20220406
LR  - 20220406
IS  - 1436-3771 (Electronic)
IS  - 1432-6981 (Linking)
VI  - 26
IP  - 4
DP  - 2022 Apr
TI  - Periodontal ligament cells under mechanical force regulate local immune 
      homeostasis by modulating Th17/Treg cell differentiation.
PG  - 3747-3764
LID - 10.1007/s00784-021-04346-0 [doi]
AB  - OBJECTIVES: Improper orthodontic force often causes root resorption or 
      destructive bone resorption. There is evidence that T helper 17 (Th17) cells and 
      regulatory T (Treg) cells may be actively involved in bone remodeling during 
      tooth movement. In a combination of in vitro and in vivo studies, we investigated 
      the effect of human periodontal ligament cells (hPDLCs) on Th17/Treg cells under 
      different orthodontic forces and corticotomy. MATERIAL AND METHODS: hPDLCs were 
      cultured in vitro and subjected to different mechanical forces. The expression of 
      interleukin (IL)-6 and transforming growth factor (TGF)-beta in the supernatant and 
      the mRNA levels of hypoxia inducible factor (HIF)-1alpha, Notch1, and TGF-beta in hPDLCs 
      were investigated. Supernatants were collected and co-cultured with activated 
      CD4(+)T cells, and the differentiation of Th17/Treg cells was analyzed by flow 
      cytometry. We also established an animal model of tooth movement with or without 
      corticotomy. The tooth movement distance, alveolar bone height, and root 
      resorption were analyzed using micro-computed tomography. Expression of 
      interleukin (IL)-17A, forkhead Box P3 (Foxp3), and IL-6 were analyzed using 
      immunohistochemistry, while osteoclasts were evaluated by tartrate-resistant acid 
      phosphatase (TRAP) staining. The mRNA levels of IL-17A, IL-6, Foxp3, IL-10, 
      HIF-1alpha, notch1, and C-X-C motif chemokine ligand 12 (CXCL12) in alveolar bone and 
      gingiva were investigated. RESULTS: Heavy force repressed cell viability and 
      increased the mortality rate of hPDLCs; it also improved the expression of IL-6, 
      declined the expression of TGF-beta, and promoted the mRNA expression level of 
      HIF-1alpha. The expression of TGF-beta and Notch1 mRNA decreased and then increased. The 
      supernatant of hPDLCs under heavy force promotes the polarization of Th17 cells. 
      The heavy force caused root resorption and decreased alveolar bone height and 
      increased the positive area of IL-17A immunohistochemical staining and the 
      expression of IL-17A, IL-6, HIF-1alpha, and Notch1 mRNA. Corticotomy accelerated 
      tooth movement, increased the proportion of Foxp3-positive cells, and 
      up-regulated the expression of Foxp3, IL-10, and CXCL12 mRNA. CONCLUSIONS: During 
      orthodontic tooth movement, the heavy force causes root resorption and 
      inflammatory bone destruction, which could be associated with increased 
      expression of Th17 cells and IL-6. Corticotomy can accelerate tooth movement 
      without causing root resorption and periodontal bone loss, which may be related 
      to the increased expression of Treg cells. CLINICAL RELEVANCE: Altogether, this 
      report provides a new perspective on the prevention of inflammatory injury via 
      the regulation of Th17/Treg cells in orthodontics.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Lin, Jiayu
AU  - Lin J
AD  - Department of Orthodontics, Stomatological Hospital, Southern Medical University, 
      No.366, Jiangnan Avenue South, Guangzhou, 510280, China.
FAU - Huang, Jiachang
AU  - Huang J
AD  - Department of Orthodontics, Stomatological Hospital, Southern Medical University, 
      No.366, Jiangnan Avenue South, Guangzhou, 510280, China.
FAU - Zhang, Zhaoqiang
AU  - Zhang Z
AD  - Department of Oral and Maxillofacial Surgery, Stomatological Hospital, Southern 
      Medical University, No.366, Jiangnan Avenue South, Guangzhou, 510280, China.
FAU - Yu, Xinyi
AU  - Yu X
AD  - Department of Orthodontics, Stomatological Hospital, Southern Medical University, 
      No.366, Jiangnan Avenue South, Guangzhou, 510280, China.
FAU - Cai, Xuepei
AU  - Cai X
AD  - Department of Orthodontics, Stomatological Hospital, Southern Medical University, 
      No.366, Jiangnan Avenue South, Guangzhou, 510280, China.
FAU - Liu, Chufeng
AU  - Liu C
AUID- ORCID: 0000-0002-3995-0148
AD  - Department of Orthodontics, Stomatological Hospital, Southern Medical University, 
      No.366, Jiangnan Avenue South, Guangzhou, 510280, China. xyzmmok@smu.edu.cn.
LA  - eng
GR  - No. 2018A0303130261/natural science foundation of guangdong province/
PT  - Journal Article
DEP - 20220114
PL  - Germany
TA  - Clin Oral Investig
JT  - Clinical oral investigations
JID - 9707115
MH  - *Alveolar Bone Loss/prevention & control
MH  - Animals
MH  - Cell Differentiation
MH  - Homeostasis
MH  - Periodontal Ligament
MH  - *T-Lymphocytes, Regulatory/metabolism
MH  - Th17 Cells/metabolism
MH  - Tooth Movement Techniques
MH  - X-Ray Microtomography
OTO - NOTNLM
OT  - Corticotomy
OT  - Orthodontics
OT  - Periodontal ligament cells
OT  - Th17 cells
OT  - Treg cells
EDAT- 2022/01/15 06:00
MHDA- 2022/04/07 06:00
CRDT- 2022/01/14 12:18
PHST- 2021/08/02 00:00 [received]
PHST- 2021/12/11 00:00 [accepted]
PHST- 2022/01/15 06:00 [pubmed]
PHST- 2022/04/07 06:00 [medline]
PHST- 2022/01/14 12:18 [entrez]
AID - 10.1007/s00784-021-04346-0 [pii]
AID - 10.1007/s00784-021-04346-0 [doi]
PST - ppublish
SO  - Clin Oral Investig. 2022 Apr;26(4):3747-3764. doi: 10.1007/s00784-021-04346-0. 
      Epub 2022 Jan 14.