Discovery of metabolite biomarkers for odontogenic keratocysts.

INTRODUCTION: Odontogenic keratocysts (OKCs) are locally aggressive and have a high rate of recurrence, but the pathogenesis of OKCs is not fully understood. We aimed to investigate the serum metabolomic profile of OKCs and discover potential biomarkers. METHODS: Metabolomic analysis was performed on 42 serum samples from 22 OKC patients and 20 healthy controls (HCs) using gas chromatography‒mass spectrometry to identify dysregulated metabolites in the OKC samples. LASSO regression and receiver operating characteristic (ROC) curve analyses were used to select and validate metabolic biomarkers and develop diagnostic models. RESULTS: A total of 73 metabolites were identified in the serum samples, and 24 metabolites were dysregulated in the OKC samples, of which 4 were upregulated. Finally, a diagnostic panel of 10 metabolites was constructed that accurately diagnosed OKCs (sensitivity of 100%, specificity of 100%, area under the curve of 1.00). CONCLUSION: This study is the first to investigate the metabolic characteristics and potential metabolic biomarkers in the serum of OKC patients using GC‒MS. Our study provides further evidence to explore the pathogenesis of OKC.

Regenerative Endodontic Treatment in Dentinogenesis Imperfecta-Induced Apical Periodontitis.

Pulp involvement of immature permanent teeth with dentinogenesis imperfecta is challenging and could lead to extraction. A case of dentinogenesis imperfecta-induced periapical periodontitis of an immature permanent tooth was treated with regenerative endodontic treatment (RET), and root maturation was observed in 12-month follow-up. An 8-year-old girl presented acute pain and swelling in central mandibular region. Clinical and radiographic examination revealed "shell teeth" appearance of teeth 31, 41, and 42. Periapical lesion of tooth 31 was observed. Tooth 41 was previously treated with apexification. RET was planned and carried out for the necrotic tooth (tooth 31) with dentinogenesis imperfecta. The 1-, 3-, 7-, and 12-month postoperative recall revealed complete healing of periapical lesions. Root maturation characterized by elongation of root, thickening of dentinal walls, and closure of root apex was observed with radiographic examinations. We show that RET could be a desirable treatment for necrotic immature permanent teeth with dentinogenesis imperfecta and lead to resolution of endodontic lesions as well as maturation of dental root. The findings of this case suggest that RET should be considered by endodontist and pediatric dentist to treat teeth with similar dental anomalies and apical periodontitis.

Effects of different signaling pathways on odontogenic differentiation of dental pulp stem cells: a review.

Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cells that can differentiate into odontoblast-like cells and protect the pulp. The differentiation of DPSCs can be influenced by biomaterials or growth factors that activate different signaling pathways in vitro or in vivo. In this review, we summarized six major pathways involved in the odontogenic differentiation of DPSCs, Wnt signaling pathways, Smad signaling pathways, MAPK signaling pathways, NF-kB signaling pathways, PI3K/AKT/mTOR signaling pathways, and Notch signaling pathways. Various factors can influence the odontogenic differentiation of DPSCs through one or more signaling pathways. By understanding the interactions between these signaling pathways, we can expand our knowledge of the mechanisms underlying the regeneration of the pulp-dentin complex.

Er:YAG laser therapy in combination with GLUMA desensitizer reduces dentin hypersensitivity in children with molar-incisor hypomineralization: a randomized clinical trial.

This study aimed to investigate the effectiveness of erbium-doped yttrium garnet (Er:YAG) laser and GLUMA desensitizer for dentin hypersensitivity in teeth affected by Molar-Incisor Hypomineralization (MIH). One hundred twenty children were randomly allocated to four groups: the control (Co) group, the desensitizer (De) group, the laser (La) group, and the laser + desensitizer (La + De) group. Outcome measures included Visual Analogue Scale (VAS) and 14-item Oral Health Impact Profile (OHIP-14) evaluation. For mean VAS scores, a significant reduction was found over time in all groups. Co and De groups, Co and La groups, Co and La + De groups, De and La + De groups, and La and La + De groups differed significantly (p < 0.05). For mean scores in all dimensions of OHIP-14 after treatment 6 months, the La + De group was significantly lower (p < 0.001). The La + De groups and the La groups as well as the La + De groups and the De groups differed significantly in total OHIP, functional limitation, physical disability, and psychological disability (p < 0.05). Physical pain between the La + De groups and the La groups and handicap between the La + De groups and De groups differed significantly (p < 0.05). The mean values of each dimension differed significantly between the group Co and the La + De group (p < 0.0001). Combination therapy of Er:YAG laser and GLUMA desensitizer had greater desensitizing effects and oral health-related quality improvement of life, which might be an effective alternative treatment in dentin hypersensitivity in MIH children.

Evaluation of Chitosan-Oleuropein Nanoparticles on the Durability of Dentin Bonding.

Purpose: To evaluate the effects of dentin pretreatment with chitosan-loaded oleuropein nanoparticles (CONPs) on the durability of resin-dentin bonding interfaces. Methods: Eighty freshly extracted non-carious human third molars were randomly divided into four groups (n = 20 each): a de-ionized water (DW) group, a chitosan (CS) group, a chlorhexidine (CHX) group and a CONP group. The dentin in the DW, CS, CHX, and CONP groups were pretreated with de-ionized water, 1.0 mg/L CS solution, 2% chlorhexidine solution, and CONP suspension (prepared with 100 mg/L oleuropein), respectively, followed by the universal adhesive and resin composites. The bonded teeth of each group were randomly divided into two subgroups: an immediate subgroup and an aged subgroup. The bonded teeth of each group were then cut into the bonded beams. We measured their microtensile bond strength (µTBS), observed the characteristics of bonding interface by atomic force microscope, calculated the percentage of silver particles in a selected area for interfacial nanoleakage analysis, and evaluated the endogenous gelatinase activity within the bonding interface for in-situ zymogram analysis. Data were analyzed with two-way ANOVA and LSD multiple comparison test (P < 0.05). Results: Regardless of after 24 h or after thermocycling, CONP exhibited better µTBS (P < 0.05) than the other three groups except that there was not a statistical significance (P > 0.05) in the CONP and CHX groups after 24 h. Besides, the CONP group presented significantly higher modulus of elasticity in the hybrid layers (P < 0.05), lower expression of nanoleakage (P < 0.05), and better inhibitory effect of matrix metalloproteinases than the other three groups before and after thermocycling. Conclusion: Altogether, the CONPs had the potential to act as a dentin primer, which could effectively improve the dentin-resin binding durability.

Effect of chitosan-oleuropein nanoparticles on dentin collagen cross-linking.

BACKGROUND: The integrity and stability of collagen are crucial for the dentin structure and bonding strength at dentin-resin interface. Natural plant-derived polypehenols have been used as collagen crosslinkers. OBJECTIVE: The aims of the study were to develop novel chitosan oleuropein nanoparticles (CS-OL-NPs), and to investigate the CS-OL-NPs treated dentin's the resistance to enzymatic degradation and mechanic property. METHODS: CS-OL-NPs were developed using the ionotropic gelation method. Release and biocompatibility of the CS-OL-NPs were tested. Twenty demineralized dentin collage specimens were randomized into four interventions groups: A, Deionized Water (DW); B, 5% glutaraldehyde solution (GA); C, 1 mg/ml chitosan (CS); and D, 100 mg/L CS-OL-NPs. After 1-min interventions, dentin matrix were evaluated by the micro-Raman spectroscopy for the modulus of elasticity test. Collagen degradation was assessed using hydroxyproline (HYP) assay. RESULTS: CS-OL-NPs were spherical core-shape with a size of 161.29 ± 8.19 nm and Zeta potential of 19.53 ± 0.26 mV. After a burst release of oleuropein in the initial 6 h, there was a long-lasting steady slow release. CS-OL-NPs showed a good biocompatibility for the hPDLSCs. The modulus of elasticity in the crosslinked groups were significantly higher than that in the control group (P< 0.05 for all). The specimens treated with CS-OL-NP showed a greater modulus of elasticity than those treated with GA and CS (P< 0.05 for both). The release of HYP in the crosslinked group was significantly lower than that in the non-crosslinked groups (P< 0.05 for all). CONCLUSION: CS-OL-NPs enhanced the dentin mechanical property and resistance to biodegradation, with biocompatibility and potential for clinical application.

Retraction of "circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis".

[This retracts the article DOI: 10.1515/med-2022-0442.].

circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis.

CircularRNAs (circRNAs) are collectively involved in periodontitis. The aim of this study was to explore the roles of circ_0062491 in osteogenic differentiation of PDLSCs and provide a novel method for periodontitis treatment. mRNA and protein expression levels were measured by qRT-PCR and western blotting. Alkaline phosphatase (ALP) and alizarin red S (ARS) staining were used to detect the activity of osteogenesis. Furthermore, the interactions between miR-142-5p and circ_0062491/IGF1 were verified by a luciferase reporter assay. circ_0062491 was suppressed in PDL tissues of periodontitis patients and overexpressed in osteogenesis-induced PDLSCs. Upregulated circ_0062491 promoted osteogenic differentiation of PDLSCs. miR-142-5p was verified to be a target of circ_0062491, and the overexpression of miR-142-5p suppressed the osteogenic differentiation of PDLSCs induced by circ_0062491 Additionally, miR-142-5p targeted IGF1, and silenced IGF1 abrogated the effects of suppressed miR-142-5p on osteogenic differentiation of PDLSCs. In conclusion, circ_0062491 acted as a competing endogenous RNA to regulate osteogenic differentiation of PDLSCs via the miR-142-5p/IGF1 axis.

Prevalence of early childhood caries in three regions of China: A cross-sectional study.

BACKGROUND: The burden of early childhood caries (ECC) in different regions of China with different levels of economic development has been of interest to policymakers and public health workers. AIM: To investigate regional differences in ECC prevalence in China and to identify associated risk factors. METHODS: A total of 11 612 three- to five-year-old children from three geographic regions of China were included in this cross-sectional study. The dmft index was assessed for each child. A questionnaire regarding children's dietary habits, oral health behaviors, parents' socioeconomic status, and attitudes toward oral health was administered. Odds ratios and 95% confidence intervals were calculated to evaluate associated factors. RESULTS: Caries prevalence in the Eastern, Central and Northwestern regions of China was 63.4% (95% CI: 61.4%-64.5%), 59.4% (95% CI: 58.6%-61.7%), and 59.0% (95% CI: 58.5%-61.6%), respectively. Children from the Northwestern (OR = 0.83, 95% CI: 0.75-0.92) and Central (OR = 0.83, CI: 0.75-0.92) regions of China had a lower risk of experiencing ECC. Dietary habits and parents' specific oral health knowledge and attitudes were associated with ECC. CONCLUSIONS: Differences in ECC prevalence were found in the three regions of China. Multiple factors were associated with ECC. Overall, the burden of ECC was heavy in the examined regions.

Stimulatory effects of simvastatin on bone regeneration of the expanded suture in rats.

Simvastatin belongs to the family of statins and is found to have some osteopromotive properties in recent years. The aim of the present study was to investigate the potential effects of simvastatin on bone formation of the expanded mid-palatal suture of rats. Forty-five Wistar rats were randomly divided into three groups: control (C), expansion (EP), and expansion plus simvastatin (ES) groups. Rats in the ES group were administrated with simvastatin (20 mg/kg/d body weight). According to the schedule of sacrifice (days 3, 7 and 14), the suture width and bone volume changes of the region of interest (ROI) were detected by micro-computed tomography during RME. Besides, morphological changes and bone morphogenetic protein 2 (BMP-2) expression in the mid-palatal suture were observed by hematoxylin and eosin (HE) and immunohistochemical staining. Kruskal-Wallis one-way analysis of variance (ANOVA) and LSD method were applied to analyze the data at P<0.05 level. By the RME appliance, the suture was successfully widened. On days 7, 14, the bone volume of ROI in the ES group was more than that in the EP group (P<0.05). Besides, histological examinations also demonstrated that more bone regeneration and capillaries in the suture in the ES group were observed than that in the EP group. The BMP-2 expression in the ES group was more (P<0.05) than that in the EP and C groups on days 3, 7, 14. Consequently, those findings showed that simvastatin can induce a favorable effect on bone regeneration in the mid-palatal suture of rats during RME.

Differential effects of high-physiological oestrogen on the degeneration of mandibular condylar cartilage and subchondral bone.

The striking predilection of temporomandibular disorders (TMD) in women, especially during gonad-intact puberty or reproductive years, indicates that oestrogen plays an important role in the progression of TMD, but the underlying mechanism remains unclear. In this study, unilateral anterior crossbite (UAC) was used to create temporomandibular joint osteoarthritis (TMJ OA) models in rats, while 17ß-estradiol (E2) injections were applied to mimic patients with high-physiological levels of oestrogen. Micro-CT scanning, histological staining and real-time PCR assays were preformed to observe the degenerative changes in the mandibular condylar cartilage and subchondral bone. The results showed that obvious degradation was found in the condylar cartilage and subchondral bone of rats with UAC procedure, including decreased cartilage thickness, loss of extracellular matrix, increased apoptotic chondrocytes and expression of pro-inflammatory and catabolic factors, decreased bone mineral density and increased osteoclast activity. E2 supplements aggravated the condylar cartilage degradation but reversed the abnormal bone resorption in the subchondral bone induced by UAC. Our results revealed that high-physiological oestrogen plays a destructive role in condylar cartilage but a protective role in subchondral bone at the early stage of TMJ OA. These dual and distinct effects should be given serious consideration in future OA treatments.

FOXP3 inhibits cancer stem cell self-renewal via transcriptional repression of COX2 in colorectal cancer cells.

Colon cancer stem cell (cCSC) is considered as the seed cell of colon cancer initiation and metastasis. Cyclooxygenase-2 (COX2), a downstream target of NFκB, is found to be essential in promoting cancer stem cell renewal. However, how COX2 is dysregulated in cCSCs is largely unknown. In this study, we found that the expression of transcription factor FOXP3 was much lower in the spheroids than that in the parental tumor cells. Overexpression of FOXP3 significantly decreased the numbers of spheres, reduced the side population. Accordingly, FOXP3 expression decreased the tumor size and weight in the xenograft model. The tumor inhibitory effects of FOXP3 were rarely seen when COX2 was additionally knocked down. Mechanically, FOXP3 transcriptionally repressed COX2 expression via interacting with and thus inhibiting p65 activity on the putative NFκB response elements in COX2 promoter. Taken together, we here revealed possible involvement of FOXP3 in regulating cCSC self-renewal via tuning COX2 expression, and thus providing a new target for the eradication of colon cancer stem cells.

Nicotine induces the production of IL-1ß and IL-8 via the α7 nAChR/NF-κB pathway in human periodontal ligament cells: an in vitro study.

BACKGROUND/AIMS: Tobacco smoking is a major risk factor for the occurrence and progression of periodontitis. We previously demonstrated that nicotine could induce the expression of α7 nicotinic acetylcholine receptors (α7 nAChR) in human and rat periodontal tissues. To further examine the signal pathways mediated by α7 nAChR in periodontal ligament (PDL) cells, we investigated whether nicotine affects interleukin-1ß (IL-1ß) and interleukin-8 (IL-8) via the α7 nAChR/NF-κB pathway in human PDL cells. METHODS: Human PDL cells were pre-incubated with alpha-bungarotoxin (α-BTX) or pyrrolidine dithiocarbamate (PDTC), then cultured with nicotine. Then, we used western blotting, a dual-luciferase reporter, real-time quantitative PCR and an enzyme-linked immunoassay to assess expression of the NF-κB p65 subunit, NF-κB activity and production of IL-1ß and IL-8 in human PDL cells. RESULTS: Compared with the control group, nicotine could significantly induce production of IL-1ß and IL-8 in human PDL cells and cause the similar effects on the expression of the NF-κB p65 subunit and NF-κB activity. CONCLUSION: This study demonstrates that nicotine could induce production of IL-1ß and IL-8 via the α7 nAChR/NF-κB pathway in human PDL cells, providing data for a better understanding of the relationships among smoking, nicotine, and periodontitis.

Changes in the expression of aromatase, estrogen receptor α and ß in mandibular condylar cartilage of rats induced by disordered occlusion.

BACKGROUND: Estrogens play an important role in modulating the morphology and function of temporomandibular joints (TMJs), which is suggested to act via estrogen receptors (ERs). The present study was to investigate the expression of aggrecan, collagen type II (Col II), Col X, aromatase, ERα and ERß in degenerative changes of mandibular condylar cartilage. METHODS: Forty male and 40 female 8-week-old rats were enrolled in this study. In experimental groups, the disordered occlusion was created by moving the first molars mesially and the third ones distally. Immunohistochemistry and real-time PCR were performed at the end of the second or fourth week. RESULTS: Degenerative changes, characterized by interrupted continuity of hypertrophic layer, pyknotic and eosinophilic lesion with few nuclei, areas filled with eosinophilic nuclei, were observed in more joints from female experimental groups than male ones. However, thickening changes in hypertrophic layer were only found in male experimental groups. The gene expression of Col II, Col X and aggrecan increased in 4-wk male experimental subgroup (both P < 0.01), but decreased in 2-wk and 4-wk female subgroups (P < 0.05). The gene expression of ERα decreased in 2-wk male and female experimental subgroups (both P < 0.01), however, that of ERß increased except the 2-wk female experimental subgroup (all P < 0.01). The expression of aromatase decreased in both male and female experimental subgroups (all P<0.01). CONCLUSIONS: Mandibular condylar cartilage responses differently to the disordered occlusion in male and female rats. The levels of locally synthesized estrogen, ERα and ERß may have limited attribution, if any, to the sex-specific cartilage response.

Excess genistein suppresses the synthesis of extracellular matrix in female rat mandibular condylar cartilage.

AIM: To investigate the effect of excess genistein on the extracellular matrix in mandibular condylar cartilage of female rats in vivo. METHODS: Female SD rats were administered through oral gavage with genistein (50 mg/kg) or placebo daily for 6 weeks. The morphological changes of temporomandibular joints were studied with HE staining. The expression of cartilage matrix compounds (aggrecan and collagen type II), estrogen-related molecules (aromatase, estradiol, ERα and ERß) and proliferating cell nuclear antigen (PCNA) in mandibular condylar cartilage was detected using immunohistochemistry, ELISA and real-time PCR. RESULTS: The genistein treatment significantly reduced the thickness of the posterior and middle regions of mandibular condylar cartilage, and decreased the expression of collagen type II, aggrecan and PCNA. Compared with the control group, the estradiol content and expression levels of the key estradiol-synthesizing enzyme aromatase in the genistein-treatment group were significantly decreased. The genistein treatment significantly increased the expression of ERß, but decreased the expression of ERα. CONCLUSION: Excess genistein suppresses extracellular matrix synthesis and chondrocytes proliferation, resulting in thinner mandibular condylar cartilage. These effects may be detrimental to the ability of mandibular condylar cartilage to adapt to mechanical loads.

Dose-dependent effects of genistein on bone homeostasis in rats' mandibular subchondral bone.

AIM: To investigate the effect of genistein on bone homeostasis in mandibular subchondral bone of rats. METHODS: Female SD rats were administered with genistein (10 and 50 mg/kg) or placebo by oral gavage for 6 weeks. Then the animals were sacrificed, and histomorphology and micro-structure of mandibular condyle were examined using HE staining and micro-CT analysis, respectively. The expression levels of alkaline phosphatase (ALP), osteocalcin (OC), osteoprotegerin (OPG), the receptor activator of nuclear factor κB ligand (RANKL) and estrogen receptors (ERs) in mandibular condyle were detected using real-time PCR. Cultured osteoblasts were prepared from rat mandibular condyle for in in vitro study. The cells were treated with genistein (10(-7) or 10(-4) mol/L) for 48 h. The expression of the bone homeostasis-associated factors and estrogen receptors (ERs) was detected using real-time PCR, and ER silencing was performed. RESULTS: At both the low- and high-doses, genistein significantly increased the bone mineral density (BMD) and bone volume, and resulted in thicker subchondral trabecular bone in vivo. In both in vivo and in vitro study, the low-dose genistein significantly increased the expression of ALP, OC and OPG, but decreased the expression of RANKL and the RANKL/OPG ratio. The high-dose genistein decreased the expression of all these bone homeostasis-associated factors. Both the low and high doses of genistein significantly increased the expression of ERß, while ERα expression was increased by the low dose genistein and decreased by the high dose genistein. ERß silencing abrogated most of the effects of genistein treatment. CONCLUSION: In rat mandibular condylar subchondral bone, low-dose genistein increases bone formation and inhibit bone resorption, while excess genistein inhibits both bone formation and resorption. The effects of genistein were predominantly mediated through ERß.

Pediatric Wegener's granulomatosis with oral ulcers and progressive periodontitis: a case report.

Wegener's granulomatosis (WG) is a rare multisystem disorder. Although it can occur at any age, it is rarely observed in children. Oral manifestations, which are present in fewer than 10% of patients, include oral ulceration, nonhealing extraction sockets, and the most common oral lesion, hyperplastic gingivitis, which is known as "strawberry gingivitis." We report the unusual case of a 6-year-old boy with WG who presented with atypical oral manifestations, including severe progressive periodontitis accompanied by oral ulcers, before the development of systemic symptoms. Although WG is rare, this case emphasizes the importance of considering the diagnosis in those who present with progressive and atypical oral disease, as prompt treatment of the systemic illness can significantly improve outcome.

Locally synthesized estrogen plays an important role in the development of TMD.

Estrogens have been suggested to play an important role in the development of temporomandibular disorders (TMD). However, a growing body of epidemiological, clinical and experimental researches focusing on the relationship between TMD and exogenous estrogen or serum estrogen has produced conflicting results. Recently, locally synthesized estrogens have been found and proved to contribute greatly to the function of cartilage. We hypothesize that estrogens synthesized locally in condylar cartilage have a profound effect on the development of TMD. Future investigation of local estrogen in condylar cartilage may give, at least partially, valuable evidences for the etiology and treatment strategy of TMD. In our opinion, regulating the amount and effect of locally synthesized estrogen seems to hold interesting future prospects for the treatment of TMD.

Influence of the location of the parotid duct orifice on oral clearance.

OBJECTIVES: To determine the location of the parotid duct orifice in relation to the maxillary molars and its influence on oral clearance on the buccal surfaces of the maxillary molars. METHODS: A 2-mm hole was made at the centre of an adhesive therapeutic agent for aphthous stomatitis and the agent was placed on the mucosa so that the hole matched the parotid duct orifice. To locate the orifice, an impression of the buccal tooth surfaces and mucosa around the agent was taken with the teeth in centric occlusion. To evaluate the oral clearance rate, 12 subjects who displayed the parotid duct orifice within 1S.D. of the mean values obtained from the original 35 subjects were selected. 1% agar containing 1 mol/l potassium chloride was placed into three cylinders positioned horizontally, 6mm apart, in an acrylic holder centred over the mean duct location. The diffusion chambers were taken from the mouth at selected time intervals and the gel transferred quantitatively to flasks containing 300 ml of 100 ppm NaCl, which was assayed for potassium by atomic absorption spectrophotometry. Half-times for clearance were calculated. RESULTS: The mean location of the parotid duct orifice was -0.4 mm (range -7.5 to +6.1 mm) mesial to the contact surface between the maxillary first and second molars (where negative values indicate mesial and positive values distal) and 7.2 mm (range +3.8 to +10.4 mm) above a line touching the buccal cusps of the upper molars. The clearance half-time values were shortest for the central cylinder whether salivary flow was unstimulated or stimulated and when flow was unstimulated the clearance half-time was shorter for the mesial than the distal cylinder. CONCLUSION: The degree of individual variation in the location of the parotid duct orifice is great and its exact location will markedly affect oral clearance at different positions on the buccal surfaces of the upper molars.

[Expression feature and bioinformatic analysis of molar root patterning gene 1].

OBJECTIVE: To examine the expression of molar root patterning gene 1 (Mrp1) and predict the Mrp1 structure by bioinformatics analysis. METHODS: A pair of Mrp1-specific PCR primers were designed, and RT-PCR method was used to study the mRNA's expression pattern in rat molar root and other organs. Gene positioning and other protein sequence prediction were carried out by chromosome analysis and other bioinformatics analysis. RESULTS: Mrp1 was expressed not only in the molar but also in the developing pancreas, liver, lung and kidney tissues. Mrp1 was located in the 18q12.3 chromosome of the rats and the Mrp1 amino acids sequence had about 37% homology with a known protein Uroplakin IIIb (p35) which was an urothelial differentiation membrane molecular marker. A trans-membrane structure, 5 PKC phosphorylation sites and 4 CKII phosphorylation sites in Mrp1 were found. CONCLUSIONS: Mrp1 has a broad expression in different developing organs, and it may have a important function in the rat tooth root development.