期刊
JOURNAL OF DENTAL RESEARCH
卷 101, 期 6, 页码 695-703出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/00220345211062585
关键词
periodontal ligament; Wnt signaling pathway; osteogenesis; cellular mechanotransduction; orthodontics; cell lineage
资金
- US National Institutes of Health [DE030643, DE025659]
The Wnt-beta-catenin signaling pathway is crucial in orthodontic tooth movement, with Axin2(+) PDL cells being highly sensitive to orthodontic tension force and playing a critical role in PDL expansion and alveolar bone formation during the process. Targeting Axin2(+) PDL progenitor cells in future drug development may accelerate alveolar bone formation in orthodontic treatment.
Wnt-beta-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-beta-catenin levels and Axin2(+) PDL progenitor cell numbers during OTM using immunostaining of beta-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 (Axin2(CreERT2/+); R26R(tdTomato/+)). Coimmunostaining images displayed both early and late bone markers (such as RUNX2 and DMP1) in the Axin2(Lin) 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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