Project description:Purpose : This study was performed to investigate the changes in gene expression in periodontal ligament (PDL) cells following mechanical stimulus through RNA sequencing. Method : Premolars extracted for orthodontic treatment were used. To stimulate the PDL cells, an orthodontic force of 100× g was applied to the premolar (experimental group; n = 11), whereas the tooth on the other side was left untreated (control group; n = 11). After the PDL cells were isolated from the extracted teeth, gene set enrichment analysis (GSEA), differentially expressed gene (DEG) analysis, and real-time PCR were performed to compare the two groups. Result : GSEA demonstrated that gene sets related to the cell cycle pathway were upregulated in PDL. Thirteen upregulated and twenty downregulated genes were found through DEG analysis. Real-time PCR results confirmed that five upregulated genes (CC2D1B, CPNE3, OPHN1, TANGO2, and UAP-1) and six downregulated genes (MYOM2, PPM1F, PCDP1, ATP2A1, GPR171, and RP1-34H18.1-1) were consistent with RNA sequencing results. Conclusion : Two upregulated genes, CPNE3 and OPHN1, and one downregulated gene, PPM1F, play an important role in PDL regeneration in humans when orthodontic force is applied.
Project description:In orthodontic therapy periodontal tissue responds to mechanical stimuli by bone remodeling mediated by specific molecules involved in periodontal regeneration and homeostasis. The resulting changes are reflected in the salivary proteome that is emerging as a valuable diagnostic tool. We analyzed the changes of saliva proteome during orthodontic tooth movement in 12 healthy male patients, presented with malocclusion treated by placement of fixed orthodontic appliance. Six patients with identical dental pathology, but no orthodontic therapy were used as control samples. Saliva was collected a day before, immediately after, and 2, 7 and 30 days after the placement of the fixed orthodontic appliance and analyzed by LC-MS. Total of 198 proteins were identified and classified on the basis of their functional characteristics. Proteins involved in bone remodeling, inflammation and healing were detected mostly 30 days after placement of the fixed orthodontic appliance. At this time point, Bone morphogenetic protein 4 emerged as a central player in the ongoing dental bone remodeling. Besides BMP4, BMP antagonists: BMP Binding Endothelial Regulator (BMPER), Insulin-like growth factor-binding protein 3 (IGFBP3), Cytoskeleton-associated protein 4 (CKAP4) and Fibroblast growth factor 5 (FGF5), were also identified. Presence of BMP4 in human saliva 30 days after the placement of orthodontic fixed appliance was confirmed by ELISA and concentration of BMP4 was 3.2 pg/ml. To date, there is no published data on the presence of BMP molecules or their antagonists in saliva or the gingival cervical fluid, regardless of different orthodontic treatments or disease. BMP4 is involved not only in orthodontic treatment, but also in processes involving tooth development and homeostasis. Therefore, a better understanding of its networks in bone remodeling during OTM is heralded.
Project description:Corticision is a common technique to accelerate orthodontic tooth movement; however, not much is known about the underlying mechanisms. In this study, we investigated the mechanism of alveolar tissue remodeling after corticision in a rat model of tooth movement (TM) by analyzing the differential transcriptome
Project description:To investigate the underlying mechanisms in the the states of apical periodontitis, we extracted RNA from control alveolar bone and alveolar bone under apical periodontitis.
Project description:We used single cell RNA sequencing (SCRNA-seq) to analyze the diffenrence in cell population in the alveolar bone before and after orthodntic tooth movement
Project 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.
Project description:Orthodontic tooth movement (OTM) relies on mechanical force-induced bone remodeling. As a metabolic intermediate of glycolysis, lactate has recently been discovered to participate in bone remodeling by serving as a signaling molecule. However, whether lactate could respond to mechanical stimulus during OTM, as well as whether lactate has an impact on the alveolar bone remodeling during orthodontics, remain to be further elucidated. In the current study, we observed physiologically elevated production of lactate along with increased osteogenic differentiation, proliferation, and migration of alveolar bone marrow mesenchymal cells (ABMMCs) under mechanical force. Inhibition of lactate, induced by cyclic mechanical stretch by GNE-140, remarkably suppressed the osteogenic differentiation, proliferation, and migration, yet enhanced apoptosis of ABMMCs. Mechanistically, these regulatory effects of lactate were mediated by histone lactylation. Taken together, our results suggest that force-induced lactate is involved in controlling bone remodeling-related cellular activities in ABMMCs and plays a vital role in the alveolar bone remodeling during OTM. Our findings indicate that lactate might be a critical modulator for alveolar bone remodeling during OTM, providing a novel therapeutic target for the purpose of more effectively controlling tooth movement and improving the stability of orthodontic results.