Axin2+ PDL Cells Directly Contribute to New Alveolar Bone Formation in Response to Orthodontic Tension Force

Wnt–β-catenin signaling plays a key role in orthodontic tooth movement (OTM), a common clinical practice for malocclusion correction. However, its targeted periodontal ligament (PDL) progenitor cells remain largely unclear. In this study, we first showed a synchronized increase in Wnt–β-catenin leve...

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Veröffentlicht in:Journal of dental research 2022-06, Vol.101 (6), p.695-703
Hauptverfasser: Wang, K., Xu, C., Xie, X., Jing, Y., Chen, P.J., Yadav, S., Wang, Z., Taylor, R.W., Wang, J., Feng, J.Q.
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container_end_page 703
container_issue 6
container_start_page 695
container_title Journal of dental research
container_volume 101
creator Wang, K.
Xu, C.
Xie, X.
Jing, Y.
Chen, P.J.
Yadav, S.
Wang, Z.
Taylor, R.W.
Wang, J.
Feng, J.Q.
description Wnt–β-catenin signaling plays a key role in orthodontic tooth movement (OTM), a common clinical practice for malocclusion correction. However, its targeted periodontal ligament (PDL) progenitor cells remain largely unclear. In this study, we first showed a synchronized increase in Wnt–β-catenin levels and Axin2+ PDL progenitor cell numbers during OTM using immunostaining of β-catenin in wild-type mice and X-gal staining in the Axin2-LacZ knock-in line. Next, we demonstrated time-dependent increases in Axin2+ PDL progenitors and their progeny cell numbers within PDL and alveolar bones during OTM using a one-time tamoxifen-induced Axin2 tracing line (Axin2CreERT2/+; R26RtdTomato/+). Coimmunostaining images displayed both early and late bone markers (such as RUNX2 and DMP1) in the Axin2Lin PDL cells. Conversely, ablation of Axin2+ PDL cells via one-time tamoxifen-induced diphtheria toxin subunit A (DTA) led to a drastic decrease in osteogenic activity (as reflected by alkaline phosphatase) in PDL and alveolar bone. There was also a decrease in new bone mass and a significant reduction in the mineral apposition rate on both the control side (to a moderate degree) and the OTM side (to a severe degree). Thus, we conclude that the Axin2+ PDL cells (the Wnt-targeted key cells) are highly sensitive to orthodontic tension force and play a critical role in OTM-induced PDL expansion and alveolar bone formation. Future drug development targeting the Axin2+ PDL progenitor cells may accelerate alveolar bone formation during orthodontic treatment.
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However, its targeted periodontal ligament (PDL) progenitor cells remain largely unclear. In this study, we first showed a synchronized increase in Wnt–β-catenin levels and Axin2+ PDL progenitor cell numbers during OTM using immunostaining of β-catenin in wild-type mice and X-gal staining in the Axin2-LacZ knock-in line. Next, we demonstrated time-dependent increases in Axin2+ PDL progenitors and their progeny cell numbers within PDL and alveolar bones during OTM using a one-time tamoxifen-induced Axin2 tracing line (Axin2CreERT2/+; R26RtdTomato/+). Coimmunostaining images displayed both early and late bone markers (such as RUNX2 and DMP1) in the Axin2Lin PDL cells. Conversely, ablation of Axin2+ PDL cells via one-time tamoxifen-induced diphtheria toxin subunit A (DTA) led to a drastic decrease in osteogenic activity (as reflected by alkaline phosphatase) in PDL and alveolar bone. There was also a decrease in new bone mass and a significant reduction in the mineral apposition rate on both the control side (to a moderate degree) and the OTM side (to a severe degree). Thus, we conclude that the Axin2+ PDL cells (the Wnt-targeted key cells) are highly sensitive to orthodontic tension force and play a critical role in OTM-induced PDL expansion and alveolar bone formation. 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subjects Alkaline phosphatase
Alveolar bone
Animals
Apposition
Axin Protein
beta Catenin - metabolism
Bone growth
Bone mass
Cbfa-1 protein
Dental occlusion
Diphtheria
Diphtheria toxin
Drug development
Mice
Orthodontics
Osteogenesis
Osteogenesis - physiology
Osteoprogenitor cells
Periodontal ligament
Periodontal Ligament - metabolism
Progenitor cells
Research Reports
Tamoxifen
Tamoxifen - pharmacology
Tooth Movement Techniques
Wnt protein
β-Catenin
title Axin2+ PDL Cells Directly Contribute to New Alveolar Bone Formation in Response to Orthodontic Tension Force
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