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Objective To analyze the initial displacement of the upper central incisor and stress distribution of periodontal ligament under different torque values of upper incisors under the action of a four⁃curved auxiliary arch to provide a reliable basis for the safety of clinical application of four⁃curved auxiliary arches. Methods A three⁃dimen⁃ sional finite element model for torque control of upper anterior teeth with a homemade quadrilateral auxiliary arch was established. Four different states were analyzed: molar ligation without extraction space (group A), microimplant ligation without extraction space (group B), molar recovery with extraction space closure (group C) (the adductive traction force was set at 115 g) and microimplant recovery with extraction space closure (group D) (the adductive traction force was set at 115 g). When four types of torque (0.5 N, 1.0 N, 1.5 N, and 2.0 N) were applied. The initial displacement of upper central incisors and the stress distribution of periodontal ligament in 16 groups (A1⁃A4, B1⁃B4, C1⁃C4, D1⁃D4) were ob⁃ served. Results Under different conditions, as the strength of the four⁃curve auxiliary arch increases, the maxillary an⁃ terior teeth has crown labial inclination and a root lingual inclination. The displacement of the incisor tip increases with the increase in the loading force of the torque auxiliary arch, and the displacement of the incisor root apex increases as the force increases. The difference in incisor⁃apex displacement distance in A1⁃A4, B1⁃B4, C1⁃C4, D2 and D4 groups increased as the torque force increases, while the difference between the D3 group and D1 and D2 groups decreased slightly. The stress of the cervical periodontal ligament of the upper central incisor did not exceed the stress of the peri⁃ odontal ligament in the following groups: A1, A2, B1, B2, B3, C1, C2, D1, and D2. The stress of the lip side of the up⁃ per central incisor did exceed the stress of the periodontal ligament in the following groups: A3, A4, B4, C3, C4, D3, and D4. In other words, when using the four⁃curved auxiliary arch as an implant anchorage, the force applied in the ab⁃ sence of extraction space should not exceed 1.5 N, and the force applied in the adduction of extraction space should not exceed 1.0 N. When using the nonimplant anchorage, the force applied in the absence of extraction space and the ad⁃ duction of extraction space should not exceed 1.0 N. In addition, the range of force should not exceed the maximum stress of the periodontal ligament in the cervical region such that the effective and safe torque movement can be achieved. Under other stress conditions, the stress of the labial and cervical periodontal ligament of the upper central in⁃ cisor exceeded the stress value (2.6 × 10 ⁃ 2 MPa). The stress value of periodontal ligament was 2.6 × 10 ⁃ 2 MPa in all groups. Conclusion A four⁃curved auxiliary arch has a significant effect on the upper anterior teeth, and the use of mi⁃ croimplants can better control root movement such that the crown of upper central incisors cannot be excessively lip in⁃ clined.

The normal torque angle of the maxillary anterior teeth is an important factor in the aesthetics and func⁃ tion of the anterior teeth, and torque control of the front teeth is an extremely important aspect of the correction process. At present, the normal torque angle of the front teeth is among the phase Ⅲ clinical test items recognized by the Ameri⁃ can orthodontic professional committee; consequently, good control of front teeth torque is of great significance to the aesthetics of the upper anterior teeth. In this paper, the influence of a lip appliance on the bad torque of upper anterior teeth and the associated methods of control are reviewed in detail. The advantages and disadvantages of various control methods for the anterior teeth and the significance of correct anterior teeth torque angle are summarized. The existing re⁃ search results indicate that the torsion of a straight arch wire applied directly to individual teeth is too great, making it difficult to enter the groove. Although the bending of the arch wire overcomes these shortcomings, the procedure is cum⁃ bersome; it stimulates the soft tissue of the vestibular groove and increases the patient􀆳s discomfort. The bending mecha⁃ nism of the rocking chair is more complicated; it is greatly affected by the friction between the arch wire and the brack⁃ et and is not conducive to closing the tooth extraction gap using the sliding method. The portal auxiliary arch and the single bending torque are suitable for correcting the torque angle of a single tooth. Auxiliary arch torque can be used to correct the upright upper anterior teeth during the process of closing the extraction space and after adduction; therefore, this procedure is worth popularizing. However, the accuracy of orthodontic control of anterior teeth torque requires fur⁃ ther study.

Objectives: The aim of this study was to investigate the role of p75 neurotrophin receptor (p75NTR) in regulating the mouse alveolar bone development and the mineralization potential of murine ectomesenchymal stem cells (EMSCs). Moreover, we tried to explore the underlying mechanisms associated with the PI3K/Akt/β‐catenin pathway. Materials and methods: p75NTR knockout (p75NTR−/−) mice and wild‐type (WT) littermates were used. E12.5d p75NTR−/− and WT EMSCs were isolated in the same pregnant p75NTR‐/+ mice from embryonic maxillofacial processes separately. Mouse alveolar bone mass was evaluated using micro‐CT. Differential osteogenic differentiation pathways between p75NTR−/− and WT EMSCs were analysed by RNA‐sequencing. The PI3K inhibitor LY294002 and PI3K agonist 740Y‐P were used to regulate the PI3K/Akt pathway in EMSCs. p75NTR overexpression lentiviruses, p75NTR knock‐down lentiviruses and recombined mouse NGF were used to transfect cells. Results: The alveolar bone mass was found reduced in the p75NTR knockout mouse comparing to the WT mouse. During mineralization induction, p75NTR−/− EMSCs displayed decreased osteogenic capacity and downregulated PI3K/Akt/β‐catenin signalling. The PI3K/Akt/β‐catenin pathway positively regulates the potential of differential mineralization in EMSCs. The promotive effect of p75NTR overexpression can be attenuated by LY294002, while the inhibitory effect of p75NTR knock‐down on Runx2 and Col1 expression can be reversed by 740Y‐P. Conclusion: Deletion of p75NTR reduced alveolar bone mass in mice. P75NTR positively regulated the osteogenic differentiation of EMSCs via enhancing the PI3K/Akt/β‐catenin pathway. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The aim of this study was to investigate whether sclerostin (SOST) regulates the osteogenic differentiation of rat ectomesenchymal stem cells (EMSCs) and whether SOST and low‐affinity nerve growth factor receptor (LNGFR) regulate the osteogenic differentiation of EMSCs. Materials and methods: EMSCs were isolated from embryonic facial processes from an embryonic 12.5‐day (E12.5d) pregnant Sprague‐Dawley rat. LNGFR+ EMSCs and LNGFR− EMSCs were obtained by fluorescence‐activated cell sorting and were subsequently induced to undergo osteogenic differentiation in vitro. SOST/LNGFR small‐interfering RNAs and SOST/LNGFR overexpression plasmids were used to transfect EMSCs. Results: LNGFR+ EMSCs displayed a higher osteogenic capacity and lower SOST levels compared with LNGFR− EMSCs. SOST silencing enhanced the osteogenic differentiation of LNGFR− EMSCs, while SOST overexpression attenuated the osteogenic differentiation of LNGFR+ EMSCs. Moreover, LNGFR was present upstream of SOST and strengthened the osteogenic differentiation of EMSCs by decreasing SOST. Conclusions: SOST alleviated the osteogenic differentiation of EMSCs, and LNGFR enhanced the osteogenic differentiation of EMSCs by decreasing SOST, suggesting that the LNGFR/SOST pathway may be a novel target for promoting dental tissue regeneration and engineering. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate differences of odonto-differentiation between P75-neurotrophin receptor (P75-NTR)-positive ectomesenchymal stem cells (P75+EMSCs) and P75- NTR-negative ectomesenchymal stem cells (P75+EMSCs), and their underlying mechanisms. Materials and methods: Primary cranial neural crest-derived cells (CNC) were isolated from the first branchial arches, and P75+EMSCs and P75+EMSCs were sorted by fluorescence-activated cell sorting. Differentiation of P75+EMSCs or P75+EMSCs into odontoblast-like cells was induced by dental epithelial cells in vitro or in vivo. Differential gene expression profiles between P75+EMSCs and P75+EMSCs were analysed by microarray assay. Smad4-specific small interfering RNA and activator kartogenin were used to treat the cells, to evaluate effects of Smad4 in odonto-differentiation of P75+EMSCs or P75+EMSCs. Results: Under induction of dental epithelium conditioned medium, P75+EMSCs had more mineralized node formation and higher expression of Dmp1 and Dspp compared to P75+EMSCs. In our in vivo study, graft of P75+EMSCs recombination with dental epithelium showed higher expression of DMP1 and DSP. Knock-down of Smad4 in P75+EMSCs significantly downregulated expression of DMP1 and DSP, while activation of Smad4 in P75+EMSCs by the activator kartogenin, significantly increased DSP and DMP1 expression. Conclusions: P75+EMSCs showed more odonto-differentiation potential than P75+EMSCs both in vivo and in vitro. Smad4 played a critical role in determination of odonto-differentiation potential of CNC-derived EMSCs. [ABSTRACT FROM AUTHOR]

Abstract: Several populations of stem cells, including those from the dental pulp and periodontal ligament, have been isolated from different parts of the tooth and periodontium. The characteristics of such stem cells have been reported as well. However, as a common progenitor of these cells, ectomesenchymal stem cells (EMSCs), derived from the cranial neural crest have yet to be fully characterized. The aim of this study was to better understand the characteristics of EMSCs isolated from rat embryonic facial processes. Immunohistochemical staining showed that EMSCs had migrated to rat facial processes at E11.5, while the absence of epithelial invagination or tooth-like epithelium suggested that any epithelial–mesenchymal interactions were limited at this stage. The p75 neurotrophin receptor (p75NTR), a typical neural crest marker, was used to select p75NTR-positive EMSCs (p75+ EMSCs), which were found to show a homogeneous fibroblast-like morphology and little change in the growth curve, proliferation capacity, and cell phenotype during cell passage. They also displayed the capacity to differentiate into diverse cell types under chemically defined conditions in vitro. p75+ EMSCs proved to be homogeneous, stable in vitro and potentially capable of multiple lineages, suggesting their potential for application in dental or orofacial tissue engineering. [Copyright &y& Elsevier]

Objective: The aim of this study was to investigate the spatiotemporal expression and potential role of p75NTR in tooth morphogenesis and tissue mineralization. Materials and methods: The dynamic morphology of the four stages (from the beginning of E12.5 d, then E13.5 d and E15.5 d, to the end of E18.5 d) was observed, and the expressions of p75NTR and Runx2 were traced. The ectomesenchymal stem cells (EMSCs) were harvested in vitro, and the biological characteristics were observed. Moreover, the mineralization capability of EMSCs was evaluated. The relations between p75NTR and ALP, Col‐1 and Runx2 were investigated. Results: The morphologic results showed that the dental lamina appeared at E12.5 d, the bud stage at E13.5 d, the cap stage at E15.5 d and the bell stage at E18.5 d. p75NTR and Runx2 showed the similar expression pattern. EMSCs from the four stages showed no significant difference in proliferation. But the positive rate of p75NTR in the E12.5 d cells was significantly lower than that in the other three stages (P < 0.05). Moreover, the higher positive rate of p75NTR the cells were, the stronger mineralization capability they showed. p75NTR was well positively correlated with the mineralization‐related markers ALP, Col‐1 and Runx2, which increased gradually with the mature of dental germs. Conclusion: p75NTR might play an important role in the regulation of tooth morphogenesis, especially dental hard tissue formation. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the role of p75 neurotrophin receptor (p75NTR) in regulating the mouse alveolar bone development and the mineralization potential of murine ectomesenchymal stem cells (EMSCs). Moreover, we tried to explore the underlying mechanisms associated with the PI3K/Akt/β-catenin pathway., Materials and Methods: p75NTR knockout (p75NTR -/- ) mice and wild-type (WT) littermates were used. E12.5d p75NTR -/- and WT EMSCs were isolated in the same pregnant p75NTR -/+ mice from embryonic maxillofacial processes separately. Mouse alveolar bone mass was evaluated using micro-CT. Differential osteogenic differentiation pathways between p75NTR -/- and WT EMSCs were analysed by RNA-sequencing. The PI3K inhibitor LY294002 and PI3K agonist 740Y-P were used to regulate the PI3K/Akt pathway in EMSCs. p75NTR overexpression lentiviruses, p75NTR knock-down lentiviruses and recombined mouse NGF were used to transfect cells., Results: The alveolar bone mass was found reduced in the p75NTR knockout mouse comparing to the WT mouse. During mineralization induction, p75NTR -/- EMSCs displayed decreased osteogenic capacity and downregulated PI3K/Akt/β-catenin signalling. The PI3K/Akt/β-catenin pathway positively regulates the potential of differential mineralization in EMSCs. The promotive effect of p75NTR overexpression can be attenuated by LY294002, while the inhibitory effect of p75NTR knock-down on Runx2 and Col1 expression can be reversed by 740Y-P., Conclusion: Deletion of p75NTR reduced alveolar bone mass in mice. P75NTR positively regulated the osteogenic differentiation of EMSCs via enhancing the PI3K/Akt/β-catenin pathway., (© 2020 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

Background/aims: Nuclear factor erythroid 2-related factor 2 (Nrf2) is an oncogene in various types of cancers, including oral squamous cell carcinoma (OSCC). Oxysophocarpine (OSC) is a natural alkaloid that has multiple pharmacological activities. However, the biological functions and molecular mechanism underlying the effects of OSC on the growth and metastasis of OSCC are unclear., Methods: Nrf2 levels were determined in OSCC tissues and non-cancerous specimens by quantitative real-time PCR, western blotting, and immunohistochemistry (IHC) assays. The effects of OSC on OSCC cell growth and metastasis were explored (1) using 5-ethynyl-20-deoxyuridine staining and Cell Counting Kit-8, colony formation, flow cytometry, wound-healing, Transwell, and tube formation assays in vitro; and (2) by establishing a xenograft nude mouse model in vivo. The molecular mechanisms underlying the effects of OSC on the growth and metastasis of OSCC were investigated in vitro by western blotting, caspase-3 activity, and enzyme-linked immunosorbent assays, and in vivo by western blotting and IHC assays., Results: The expression levels of Nrf2 in OSCC tissues and in cell lines were much higher than in non-cancerous tissues and normal oral keratinocytes. The upregulation of Nrf2 was positively correlated with a high incidence of lymph node metastasis and advanced histological grade and TNM stage, but inversely associated with differentiation and survival of OSCC patients. OSC reduced the expression of Nrf2 and heme oxygenase 1 (HO-1) in OSCC cells. OSC also inhibited proliferation, migration, invasion, and pro-angiogenesis of OSCC cells. Moreover, OSC induced cell cycle arrest, enhanced apoptosis of OSCC cells in vitro, and decreased OSCC tumor growth in vivo. Mechanically, OSC reduced the aggressive behavior of OSCC cells by inactivation of the Nrf2/HO-1 signaling pathway., Conclusion: Our findings provide evidence that OSC inhibits the growth and metastasis of OSCC by targeting the Nrf2/ HO-1 axis, suggesting that OSC may be a potential therapeutic agent for OSCC., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Objectives: The aim of this study was to investigate differences of odonto-differentiation between P75 -neurotrophin receptor (P75 -NTR)-positive ectomesenchymal stem cells (P75+EMSCs) and P75 -NTR-negative ectomesenchymal stem cells (P75-EMSCs), and their underlying mechanisms., Materials and Methods: Primary cranial neural crest-derived cells (CNC) were isolated from the first branchial arches, and P75+EMSCs and P75-EMSCs were sorted by fluorescence-activated cell sorting. Differentiation of P75+EMSCs or P75-EMSCs into odontoblast-like cells was induced by dental epithelial cells in vitro or in vivo. Differential gene expression profiles between P75+EMSCs and P75-EMSCs were analysed by microarray assay. Smad4-specific small interfering RNA and activator kartogenin were used to treat the cells, to evaluate effects of Smad4 in odonto-differentiation of P75+EMSCs or P75-EMSCs., Results: Under induction of dental epithelium conditioned medium, P75+EMSCs had more mineralized node formation and higher expression of Dmp1 and Dspp compared to P75-EMSCs. In our in vivo study, graft of P75+EMSCs recombination with dental epithelium showed higher expression of DMP1 and DSP. Knock-down of Smad4 in P75+EMSCs significantly downregulated expression of DMP1 and DSP, while activation of Smad4 in P75-EMSCs by the activator kartogenin, significantly increased DSP and DMP1 expression., Conclusions: P75+EMSCs showed more odonto-differentiation potential than P75-EMSCs both in vivo and in vitro. Smad4 played a critical role in determination of odonto-differentiation potential of CNC-derived EMSCs., (© 2016 John Wiley & Sons Ltd.)

Objective: To investigate the biological characteristic of ectomesenchymal stem cells (EMSC) and the differentiation of p75(+)EMSC and influencing factors., Methods: The immunohistochemical staining method was used to observe the migration of EMSC from 12.5 d SD rat embryonic facial process. Then EMSC was labeled by p75 neurotrophin receptor, and the cell cycle and stem cell surface antigens of the p75(+) EMSC was examined., Results: Immunohistochemical staining showed that stem cells from the cranial neural crest migrated to embryonic rat facial process at 12.5 days. The sorting rate of the p75(+)EMSC was 6.1%. The proportion of the p75(+)EMSCs' S/G2/M phase was stable during subculture. The special substances CD29, CD146 and Stro-1 were marked for p75(+)EMSC, and the expressions of the markers were all higher (> 90%) in p75(+) EMSC., Conclusions: The embryonic tooth did not start to grow on the conception 12.5 days of SD rats. The p75(+) EMSC after sorting had stable proliferation ability and had stem cell characteristics during subculture and didn't start differentiation.

Apert syndrome is a common craniosynostosis caused by gain-of-function missense mutations of fibroblast growth factor receptor 2 (FGFR2). Mice with the FGFR2 S252W mutation can elucidate the mechanism by which the human Apert syndrome phenotypes arise. However, many studies have focused on mutant skull and long bone malformation, only few studies have focused on mandible changes. Bone formation and micro-architecture between 28- and 56-day-old mutant mice and controls were compared to investigate the changes in the mandibular micro-architecture caused by the Fgfr2(S252W/+) mutation to provide a basis for exploring the pathogenesis and therapeutic measures of human Apert syndrome. Fgfr2(S252W/+) mutant mice were established, and their general characteristics, including weight, naso-anal length, and calcium and phosphate content in serum and bone were tested. Calcein labeling, tartrate-resistant acid phosphatase staining and toluidine blue staining were used to detect osteoblast and osteoclast activities. H&E staining and micro-CT detection were used to test micro-architecture changes. The changes in mineral apposition rate and micro-architecture of the Fgfr2(S252W/+) mice were statistically significant; however, the magnitude of the micro-architecture became less with age. The Fgfr2(S252W/+) mutation may retard mandibular bone formation, decreased bone volume, and compromised skeletal architecture by regulating both osteoblastogenesis and osteoclastogenesis., (Copyright © 2012 Wiley Periodicals, Inc.)

Background: It has been reported that Porphyromonas gingivalis is closely associated with chronic periodontitis and its detection has been recommended as a routine marker for periodontal diagnosis. The purpose of this study was to evaluate the sensitivity and specificity of a DNA probe to detect P. gingivalis in adult Chinese periodontitis patients as well as to find a rapid and convenient method to detect P. gingivalis in clinical practice., Methods: A total of 26 bacterial strains (20 reference strains and 6 clinical isolates) were collected, of which 5 were P. gingivalis and 21 were heterologous species. A DNA fragment of 542 bp, which encodes the fimbriae subunit protein (fimA) of P. gingivalis, was obtained by polymerase chain reaction (PCR) and molecular cloning techniques and used to construct the DNA probe, labeled with 32P or with digoxigenin. The constructed DNA probe was used to detect P. gingivalis in specimens collected from the periodontal pockets of 100 patients clinically confirmed with chronic periodontitis. One hundred periodontally healthy persons served as a control group., Results: Positive reactions were seen in all 5 strains of P. gingivalis while no visible reaction was found in other species. The DNA probe was capable of detecting as few as 100 P. gingivalis cells in samples. A significant difference in the positive rates of P. gingivalis between the periodontitis patients and the control group was found (P<0.01). In addition, the amount of detected P. gingivalis was positively correlated with the extent of tooth mobility, depth of periodontal pockets, and patient age (P<0.01)., Conclusion: The DNA probe is specific and sensitive for the detection of P. gingivalis in chronic periodontitis specimens and may be a suitable method for the clinical diagnosis of chronic periodontitis.