Tooth germ injury can lead to abnormal tooth development and even tooth loss, affecting various aspects of the stomatognathic system including form, function, and appearance. However, the research about tooth germ injury model on cellular and molecule mechanism of tooth germ repair is still very limited. Therefore, it is of great importance for the prevention and treatment of tooth germ injury to study the important mechanism of tooth germ repair by a tooth germ injury model. Here, we constructed a Tg(dlx2b:Dendra2-NTR) transgenic line that labeled tooth germ specifically. Taking advantage of the NTR/Mtz system, the dlx2b⁺ tooth germ cells were depleted by Mtz effectively. The process of tooth germ repair was evaluated by antibody staining, in situ hybridization, EdU staining and alizarin red staining. The severely injured tooth germ was repaired in several days after Mtz treatment was stopped. In the early stage of tooth germ repair, the expression of phosphorylated 4E-BP1 was increased, indicating that mTORC1 is activated. Inhibition of mTORC1 signaling in vitro or knockdown of mTORC1 signaling in vivo could inhibit the repair of injured tooth germ. Normally, mouse incisors were repaired after damage, but inhibition/promotion of mTORC1 signaling inhibited/promoted this repair progress. Overall, we are the first to construct a stable and repeatable repair model of severe tooth germ injury, and our results reveal that mTORC1 signaling plays a crucial role during tooth germ repair, providing a potential target for clinical treatment of tooth germ injury.
Animals ; Mice ; Mechanistic Target of Rapamycin Complex 1/pharmacology* ; Signal Transduction ; Tooth/metabolism* ; Tooth Germ/metabolism* ; Odontogenesis

OBJECTIVETo evaluate the effect of dentin matrix metalloproteinase (MMP) on the degradation of root dentin collagen.

METHODSRoot dentin powder was demineralized with acetic acid (pH 4.0) at 4 degrees C for 14 d, then dialysed and centrifuged. Precipitation was divided into 7 groups, with 6 samples in each group, and each sample was 50.0 mg. One milliliter artificial saliva with a different reagent was added in each sample respectively. The reagents were 2 mmol/L APMA (MMP activator), 2 mmol/L EDTA, 100 mmol/L EDTA, 200 mmol/L EDTA, 0.2% and 0.02% chlorhexidine (MMP inhibitor), and the blank artificial saliva was taken as control. The amount of degraded collagen of each sample was determined with hydroxyproline assay kit. Scanning electron microscope was employed to observe the morphological and structural changes of root dentin which was demineralized or put into artificial saliva after being demineralized.

RESULTSThe mean amount of degraded collagen in APMA group was significantly higher than that in the blank group (P < 0.05). The mean amount of degraded collagen in 2 mmol/L, 100 mmol/L, 200 mmol/L EDTA, 0.02% and 0.2% chlorhexidine groups was dramatically lower than that of the APMA group and the blank (P < 0.01). SEM observation indicated that the structural integrity of the collagen network on root surface dentin still existed in root dentin surface after being demineralized alone, while collagenous fibril was destructed and the structural integrity on root dentin surface disappeared after being demineralized and treated by artificial saliva.

CONCLUSIONSMMP in root dentin can degrade root dentin collagen after being activated at low pH followed by neutralization. The results suggest that host MMP may play an important role in the process of dentin caries formation.

Collagen ; metabolism ; Dental Caries ; enzymology ; Dentin ; metabolism ; Humans ; In Vitro Techniques ; Matrix Metalloproteinases ; metabolism ; Tooth Root ; metabolism

X-linked hypophosphatemia (XLH) is a rare disease of elevated fibroblast growth factor 23 (FGF23) production that leads to hypophosphatemia and impaired mineralization of bone and teeth. The clinical manifestations of XLH include a high prevalence of dental abscesses and periodontal disease, likely driven by poorly formed structures of the dentoalveolar complex, including the alveolar bone, cementum, dentin, and periodontal ligament. Our previous studies have demonstrated that sclerostin antibody (Scl-Ab) treatment improves phosphate homeostasis, and increases long bone mass, strength, and mineralization in the Hyp mouse model of XLH. In the current study, we investigated whether Scl-Ab impacts the dentoalveolar structures of Hyp mice. Male and female wild-type and Hyp littermates were injected with 25 mg·kg^-1 of vehicle or Scl-Ab twice weekly beginning at 12 weeks of age and euthanized at 20 weeks of age. Scl-Ab increased alveolar bone mass in both male and female mice and alveolar tissue mineral density in the male mice. The positive effects of Scl-Ab were consistent with an increase in the fraction of active (nonphosphorylated) β-catenin, dentin matrix protein 1 (DMP1) and osteopontin stained alveolar osteocytes. Scl-Ab had no effect on the mass and mineralization of dentin, enamel, acellular or cellular cementum. There was a nonsignificant trend toward increased periodontal ligament (PDL) attachment fraction within the Hyp mice. Additional PDL fiber structural parameters were not affected by Scl-Ab. The current study demonstrates that Scl-Ab can improve alveolar bone in adult Hyp mice.
Mice ; Male ; Female ; Animals ; Familial Hypophosphatemic Rickets/metabolism* ; Bone and Bones/metabolism* ; Tooth/metabolism* ; Periodontal Ligament/metabolism*

This study sought to determine the impact of dental fluorosis severity on demineralization and remineralization of human fluorosed teeth in vitro. Surface enamel microhardness was measured on the enamel blocks before and after demineralization and after remineralization. The results showed that after demineralization, the sequence of % Surface microhardness demineralization (% SMHD) was TFI4 (18.92 +/- 1.31) < TFI3 (20.50 +/- 1.32) < TFI2 (25.08 +/- 1.69) < TFI1 (27.77 +/- 1.79) < TFI0 (30.70 +/- 1.35) (P < 0.05), and there was no statistically significant differences between TFI1 (27.77 +/- 1.79) and the normal group TFI0 (30.70 +/- 1.35). After remineralization, the sequence of % Surface microhardness remineralization (% SMHR) was TFI1 (55.17 +/- 1.23) > TFI0 (53.97 +/- 3.05) > TFI2 (49.17 +/- 1.81) > TFI3 (44.85 +/- 1.89) > TFI4 (36.51 +/- 2.95) (P < 0.05). Moderately fluorosed enamel showed a significatnt resistance to caries, but mildly fluorosed enamel could get better remineralization. These facts and figures deserve clinicians' attention.
Dental Enamel ; chemistry ; pathology ; Fluorosis, Dental ; metabolism ; Humans ; In Vitro Techniques ; Tooth Demineralization ; Tooth Remineralization

Many studies has been conducted concerning prevention of unnecessary complications such as root resorption during orthodontic tooth movement under various mechanical forces. Nowadays, the cause of the root resorption is not thought to be confined only to mechanical forces. But the factor that affects bone metabolism are thought to be major one of the predisposing factors. The light microscope and scanning electron microscope were used to the effects of 60gm, and 100gm of tipping force on root resorption of cats, which were treated with Etidronate disodium. The results were as follows: 1. In the 60gm control group, hyalinization on the compression site of periodontal ligament appeared after first week and second week. In the 60gm experimental group, it appeared after first week with low frequency. In the 100gm control group it appeared with high frequency by first and second week while in 100gm experimental group, it appeared with low frequency. 2. In the 100gm control group, resorption of the cementum and the alveolar bone rapidly increased after second week. In the 60gm experimental group, resorption or formation of alveolar bone and cementum didn't appear all through the experimental period. 3. In the 100gm control group. formation of cementum and alveolar bone appeared after first week while in the 100gm experimental group, formation of cementum and alveolar bone appeared after second week and fourth week respectively. In the 60gm control group, formation of the cementum didn't appear all through the experimental period. 4. In the control group, the root resorption of 100gm group was higher than that of 60gm group after second week, while in experimental group, root resorption didn't appear regardless of the forces.
Animals ; Cats ; Causality ; Dental Cementum ; Etidronic Acid* ; Hyalin ; Metabolism ; Periodontal Ligament ; Root Resorption* ; Tooth Movement* ; Tooth*

Tooth number abnormality is one of the most common dental developmental diseases, which includes both tooth agenesis and supernumerary teeth. Tooth development is regulated by numerous developmental signals, such as the well-known Wnt, BMP, FGF, Shh and Eda pathways, which mediate the ongoing complex interactions between epithelium and mesenchyme. Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number; however, the underlying mechanisms remain elusive. In this review, we summarized the major process of tooth development, the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality. In addition, potential treatment approaches for tooth number abnormality based on developmental biology are also discussed. This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.
Gene Expression Regulation, Developmental ; Odontogenesis ; Signal Transduction ; Tooth/metabolism* ; Humans

OBJECTIVETo investigate the effect of removing EDTA-soluble phosphate protein in dentin on the later remineralization for the purpose of better understanding of mechanism of dentin phosphate proteins on dentin mineralization.

METHODSTo remove soluble phosphate protein by EDTA dissolution, then the remineralization rate was monitored by a constant composition crystal growth technique. The results were compared with those from the normal dentin and the dentin partially demineralized by acetic acid.

RESULTSFaster remineralization rates were found with dentin demineralized by EDTA (0.5 and 2 h) compared with normal dentin powder, while a slower rate was found with dentin demineralized by acetic acid. The increase of remineralization rate by removing phosphate protein from dentin was 100% more at 200 min after the start of the reaction.

CONCLUSIONEDTA-soluble phosphate protein in dentin has a great potential to inhibit remineralization.

Dental Cementum ; chemistry ; metabolism ; Dentin ; chemistry ; Edetic Acid ; Humans ; Phosphoproteins ; analysis ; physiology ; Tooth Demineralization ; metabolism ; Tooth Remineralization

OBJECTIVETo investigate the expression of Na(+)/Ca(2+) exchanger 1 (NCX1) channel protein in human odontoblasts (OD) and nervous tissue of dental pulp.

METHODSTwenty intact and healthy third molars extracted for orthodontic purpose were collected. The OD layer and nervous tissue were determined by dentin sialophosphoproteins (DSPP) antibody staining and modified Bielschowsky silver staining respectivelly. The immunohistochemical method was used to detect the expressions of NCX1 protein in human dental pulp tissue. The difference of expression of NCX1 in human OD at different part of dental pulp was statistically analyzed using Image Pro Plus and SPSS software.

RESULTSNCX1 channel protein was mainly expressed on the cell body of OD, and nervous tissue of dental pulp. The expression level of NCX1 on the OD of crown pulp was higher (A = 0.146 ± 0.021) than that on the upper part of root pulp (A = 0.120 ± 0.034), but the expression difference was not significant (P > 0.05).

CONCLUSIONSNCX1 channel protein was expressed on human OD and nervous tissue in dental pulp.

Dental Pulp ; innervation ; metabolism ; Dentin ; chemistry ; Humans ; Molar ; Odontoblasts ; metabolism ; Sodium-Calcium Exchanger ; metabolism ; Tooth Crown

OBJECTIVETo investigate the expression of transient receptor potential vanilloid 3 (TRPV3) ion channel protein in human odontoblasts (OD).

METHODSTwenty intact and healthy third molars extracted for orthodontic purpose were included. The quality of dental tissue sections was determined through HE staining, and the OD layer was further determined by dentin sialophosphoproteins (DSPP) antibody staining, and finally the expression of TRPV3 ion channel protein in human dental pulp tissue was examined by TRPV3 ion channel protein-specific antibody. The expression of TRPV3 channel proteins in human OD at different part of dental pulp was compared using Image Pro Plus (IPP) and SPSS software.

RESULTSTRPV3 channel protein expressed on the cell body of OD in the coronal and root pulp, and the expression in the coronal pulp was significantly higher than that in the root pulp. The TRPV3 protein also expressed at the odontoblastic process, with the higher expression in the crown (IA = 2516 ± 162) than in the root (IA = 2224 ± 150) and external root (IA = 2121 ± 92) (P < 0.05), but the expression between the lateral root area and external root area was not significantly different (P > 0.05).

CONCLUSIONSHuman odonoblasts expressed TRPV3 ion channel protein and the expression level was different at different part of dental pulp OD.

Adolescent ; Adult ; Dental Pulp ; cytology ; Humans ; Immunohistochemistry ; Odontoblasts ; cytology ; metabolism ; TRPV Cation Channels ; metabolism ; Tooth Crown ; metabolism ; Tooth Root ; metabolism ; Young Adult

Sclerostin is a Wnt signalling antagonist that controls bone metabolism. Sclerostin is expressed by osteocytes and cementocytes; however, its role in the formation of dental structures remains unclear. Here, we analysed the mandibles of sclerostin knockout mice to determine the influence of sclerostin on dental structures and dimensions using histomorphometry and micro-computed tomography (μCT) imaging. μCT and histomorphometric analyses were performed on the first lower molar and its surrounding structures in mice lacking a functional sclerostin gene and in wild-type controls. μCT on six animals in each group revealed that the dimension of the basal bone as well as the coronal and apical part of alveolar part increased in the sclerostin knockout mice. No significant differences were observed for the tooth and pulp chamber volume. Descriptive histomorphometric analyses of four wild-type and three sclerostin knockout mice demonstrated an increased width of the cementum and a concomitant moderate decrease in the periodontal space width. Taken together, these results suggest that the lack of sclerostin mainly alters the bone and cementum phenotypes rather than producing abnormalities in tooth structures such as dentin.
Animals ; Female ; Glycoproteins ; genetics ; Mice ; Mice, Knockout ; Periodontium ; metabolism ; Phenotype ; Tooth ; metabolism