Risk factors of postoperative airway obstruction complications in children with oral floor mass.

The aim of the present study was to explore the risk factors of postoperative airway complications in children with oral floor mass. The first choice of auxiliary examination method for children with oral floor mass is also proposed. This retrospective study included 50 children with floor-of-mouth (FOM) masses. Medical records were reviewed, and information on age of onset, functional impacts present, age at consultation, imaging findings, history of preoperative aspiration, pathology findings, properties of biopsied fluid, treatment modality, postoperative outcomes, and operation were recorded. A total of 20 patients exhibited functional impacts such as difficulty in breathing and feeding. Ultrasound examination was performed in 28 cases; and magnetic resonance imaging, in 38 cases. The diagnosis was lymphatic malformation in 12 cases, developmental cyst in 29 cases, and solid mass in 7 cases. There were 28 cases of surgical resection, 9 cases underwent multiple puncture volume reduction followed by surgery, 11 cases treated using sclerotherapy injection, and 1 case treated using sclerotherapy injection and surgical resection. Young age, functional impact, and high grade of lymphatic duct malformation increased the risk of surgical treatment. B-scan ultrasound is the first choice for the diagnosis of FOM masses in children.

Sandblasting increases the microtensile bond strength between resin and sclerotic dentin in noncarious cervical lesions.

PURPOSE: To evaluate the effect of sandblasting on the microtensile strength between sclerotic dentin and resin composite. METHODS: 32 premolars with noncarious cervical lesions (NCCLs) were collected, and the teeth were randomly assigned to the control group (C group) and the sandblasted group (S group). Teeth in the S group were sandblasted with 110 µm Al2O3 particles at a pressure of 75 psi, while those in the C group received no further treatment. The characteristics of the tooth surface were observed by scanning electron microscopy (SEM), and the relative area of open dentin tubules (OTs) was calculated by IPP6.0 software. Surface roughness (Ra) was also assessed. The noncarious cervical lesions of all teeth were restored with a resin composite and subsequently sectioned into sticks to measure the microtensile bond strength (µTBS). RESULTS: The mean ± SD µTBS (in MPa) of the sandblasted group was 17.9 ± 0.69 and 14.23 ± 0.44 in the control group (P< 0.05). The relative area of OTs at the gingival wall of the sandblasted group was 69.74 ± 5.23%, and 47.24 ± 7.67% in the control group (P< 0.05). The average surface roughness (µm) was 1.01 ± 0.05 in the sandblasted group and 0.16 ± 0.03 in the control group. Sandblasting could increase the bond strength of sclerotic dentin and resin restorations. CLINICAL SIGNIFICANCE: After sandblasting, the microtensile strength of sclerotic dentin on the surface of noncarious cervical lesions increased, prolonging the resin adhesion longevity. Sandblasting could also alleviate the pain of patients during the treatment process and achieve a minimally invasive treatment.

Oral health status and oral habits of children and adolescents with hemophilia: a report from the children's hemophilia comprehensive care center of China.

In recent years, the diagnosis and treatment of hemophilic children in China has significantly improved. However, oral health conditions, which affect quality of life, haven't received attention in this population. To explore the oral health status and oral hygiene of children and adolescents with hemophilia in the Children's Hemophilia Comprehensive Care Center of China. Dental and oral hygiene examinations were performed in children and adolescents with hemophilia who visited Beijing Children's Hospital. DMFT/dmft (decayed, missing, filled teeth in permanent and primary teeth) was assessed according to World Health Organization (WHO) criteria. The simplified oral hygiene index (OHI-S) was used to evaluate the oral hygiene condition of the subjects. Questionnaires were completed by their parents. SPSS 21.0 was used for statistical analysis. A total of 114 children and adolescents were enrolled. The caries prevalence was 57.4%, 72.2% and 41.2% in primary, mixed and permanent dentitions respectively. The filling rates were 14.4%, 13.9%, and 11.4%, respectively, and the OHI-S scores of the three dentition groups were 1.49 ± 0.46, 1.57 ± 0.43, and 1.76 ± 0.46, respectively. A total of 103 valid questionnaires were collected. Sixty-nine children (67%) didn't brushed their teeth 2 times a day. Nearly half of the parents knew little about fluoride toothpaste. Multiple linear regression analysis revealed that brushing teeth with the help of parents had a significant positive impact on OHI-S.  Conclusion: Dental health was unsatisfactory among hemophilic children and adolescents. The caries filling rates were low. Patients and their parents did not give much attention to oral health. What is Known: • Caries and gingivitis are the two main oral diseases that affect children with hemophilia. • However, the oral health conditions of children and adolescents with hemophilia have not received much attention in China. What is New: • This is the first study concentrating on the dental health of children with hemophilia in China. • Dental health was unsatisfactory among children and adolescents with hemophilia in China.

An infant with congenital micrognathia and upper airway obstruction was diagnosed as Hutchinson-Gilford progeria syndrome caused by a novel LMNA mutation: Case report and literature review.

Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare disease characterized by appearance of premature aging, including the skin, bones, heart, and blood vessels caused by LMNA mutation. In this study, the patient presented with congenital micrognathia and progressively aggravated upper airway obstruction as the initial symptom, which required bilateral mandibular distraction osteogenesis (MDO) surgery intervention. This was not commonly described in the literature, and the primary clinical diagnosis of Pierre Robin sequence (PRS) was made. However, other clinical features included sclerotic skin, dry skin, growth failure, lipoatrophy, joint stiffness, prominent scalp veins, small ear lobes, hair loss, and craniofacial disproportion gradually emerged, the diagnosis of HGPS was preferred when the patient was 5 months old. The genetic testing result with a novel and de novo LMNA mutation (c.1968 + 3_1968+6delGAGT) further confirmed the diagnosis and expanded the clinical and mutational spectrum of HGPS. During the 12-month follow-up period after surgery, the patient no longer suffered dyspnea. Complications of other organs and systems have not happened at the moment. In addition, the pathogenesis, the role of LMNA gene mutation, the progress in clinical treatment, and breakthrough studies about genetic treatment in animals of HGPS are described in the literature review.

Does dental caries play a role on the asthma development?-systematic review and meta-analysis.

Asthma and dental caries are the two most common diseases in children, and the relationship between them has been a focus of research. Whether dental caries affects the development of asthma has long been controversial. The aim of this study was to conduct a systematic review of the literature to assess the effect of dental caries on the development of asthma and provide new ideas for the pathogenesis and promoting factors of asthma. For a systematic review and meta-analysis, we systematically searched three databases (PubMed, Web of Science, and Embase) for studies published from database inception to 22 May 2022. We included observational studies that investigated the effect of dental caries on the development of asthma. Studies were critically appraised and a meta-analysis was performed to estimate a pooled effect. From the 845 studies initially identified, 7 of these were included in the meta-analysis. Included studies originated from America (n = 5) and Asia (n = 2). A meta-analysis of data from seven selected studies suggested that dental caries was positively associated with the risk of asthma development (The odds ratio for the pooled effect was 1.06, 95% confidence interval: 1.01, 1.10). In addition, the effect of dental caries on asthma risk varied in different geographic locations according to subgroup analyses. This study suggests that dental caries may affect the development of asthma and emphasizes the importance of increased awareness of dental care and caries prevention in patients with asthma.

Tooth Type Enhanced Transformer for Children Caries Diagnosis on Dental Panoramic Radiographs.

The objective of this study was to introduce a novel deep learning technique for more accurate children caries diagnosis on dental panoramic radiographs. Specifically, a swin transformer is introduced, which is compared with the state-of-the-art convolutional neural network (CNN) methods that are widely used for caries diagnosis. A tooth type enhanced swin transformer is further proposed by considering the differences among canine, molar and incisor. Modeling the above differences in swin transformer, the proposed method was expected to mine domain knowledge for more accurate caries diagnosis. To test the proposed method, a children panoramic radiograph database was built and labeled with a total of 6028 teeth. Swin transformer shows better diagnosis performance compared with typical CNN methods, which indicates the usefulness of this new technique for children caries diagnosis on panoramic radiographs. Furthermore, the proposed tooth type enhanced swin transformer outperforms the naive swin transformer with the accuracy, precision, recall, F1 and area-under-the-curve being 0.8557, 0.8832, 0.8317, 0.8567 and 0.9223, respectively. This indicates that the transformer model can be further improved with a consideration of domain knowledge instead of a copy of previous transformer models designed for natural images. Finally, we compare the proposed tooth type enhanced swin transformer with two attending doctors. The proposed method shows higher caries diagnosis accuracy for the first and second primary molars, which may assist dentists in caries diagnosis.

Classification specific lymphatic malformations management on head and neck in children.

OBJECTIVE: The aim of this study was to retrospectively analyze the outcomes from surgical and nonsurgical treatments for head and neck lymphatic malformations (LMs) in children. STUDY DESIGN: Fifty-eight patients were divided into a surgical group (22) and a nonsurgical group (36). The surgical group contained microcystic LMs in the tongue treated by surgery or with sclerotherapy. The nonsurgical group contained macrocystic and mixed LMs in floor of the mouth, neck, face, submandibular region, maxillofacial region and neck treated by sclerotherapy or with microwave ablation (MWA). RESULTS: In the surgical group, the mean follow-up time was 44 ± 15.3 months. At last follow-up, 15 LMs (68.2%) were completely controlled, 3 LMs (13.6%) were stable without need for further treatment, and 4 LMs (18.2%) were persistent. In the nonsurgical group, the median follow-up time was 23.5 months (13.0, 32.8). At last follow-up, 28 LMs (77.8%,) have a volume reduction rate of >50%, and 6 LMs (16.7%.) have the complication. CONCLUSIONS: Surgery is suitable for microcystic LMs in the early stage with clear boundary and becomes limited for them in the late stages due to diffuse lesions. Sclerotherapy is effective for macrocystic and mixed LMs. Sclerotherapy with MWA is exceptionally effective for large cystic LMs with multiple compartments.

Analysis of the characteristics and therapeutic effect of consonant errors in children with functional articulation disorders at different ages / 口腔疾病防治

Objective@#Analyzing the characteristics of consonant errors in children with functional dysarthria in different age groups and the effect of speech training provides a reference for clinical treatment. @*Methods @#This study followed medical ethics, and informed consent has been obtained from patients. Speech data from 388 patients with functional dysarthria were retrospectively studied. They were divided into two groups at the age of 6, namely, the preschool group (4-6 years old) of 226 patients and the school age group (6-13 years old, including 6 years old) of 162 patients. The characteristics of consonant pronunciation errors from four aspects were analyzed: average number of errors, pronunciation location, pronunciation method, and error type. One-on-one speech training was conducted, with a training frequency of once a week and once for 30 minutes. The training method was carried out in the order of phoneme training, syllable training, vocabulary training, sentence training, and short text and conversation training. The effects of speech training in the two groups were compared. @*Results@#Analysis by pronunciation location: both age groups had the highest frequency of errors in tongue tip posterior sounds; the school age group had the lowest error frequency for labiodental consonants, and the preschool group had the lowest error frequency for bilabial consonants. According to the analysis of pronunciation mode, both age groups had the highest error frequency of aspirated affricate and the lowest error frequency of nasal sound. Analysis by error type: both age groups are mainly characterized by substitution and omission. Compared with the preschool group, most consonants of patients in the school group tend to improve in terms of pronunciation location, pronunciation mode, and error types. Compared with the preschool group, the two types of errors-palatalization and lateralization-increased in frequency in the school group, but the trend of increased lateralization was not statistically significant. After 6.7 and 5.5 sessions of speech training, the pronunciation of the preschool group and the school-age group significantly improved; the cure rate of the school-age group was 84.9% (118/139), and that of the preschool group was 77.1% (91/118). There was no statistically significant difference in the cure rate between the two groups.@*Conclusion@# Functional dysarthria may improve with age, but it may not completely self-heal. Children of different age groups can achieve good treatment results through scientific and reasonable speech training.

Midpalatal Suture: Single-Cell RNA-Seq Reveals Intramembrane Ossification and Piezo2 Chondrogenic Mesenchymal Cell Involvement.

The midpalatal suture is mainly responsible for the growth and development of the maxillary and resistance to rapid maxillary expansion (RME). It is essential for clinical researchers to explore the intramembrane ossification and to elucidate the underlying mechanism of the maturation and ossification process of the midpalatal suture to help identify the optimum time and force of RME. However, mechanistic studies associated with the midpalatal suture are rare. The aim of this present study is to create an intramembrane osteogenesis model for the midpalatal suture region of mice. Interestingly, we discovered a type of chondrogenic mesenchymal cell expressing Piezo2, which might be related to the detection of mechanical and external stimuli. This result provides a potential molecular and cellular mechanism that explains why the midpalatal suture is not closed until adulthood. We depict a landscape of mesenchymal cells that might play an important role in the intramembrane osteogenesis of the midpalatal suture and provide new perspectives on midpalate suture maturation and ossification, which might lead to further possibilities for clinical operations.

Context Aware Convolutional Neural Network for Children Caries Diagnosis on Dental Panoramic Radiographs.

The objective of this study is to improve traditional convolutional neural networks for more accurate children dental caries diagnosis on panoramic radiographs. A context aware convolutional neural network (CNN) is proposed by considering information among adjacent teeth, based on the fact that caries of teeth often affects each other due to the same growing environment. Specifically, when performing caries diagnosis on a tooth, information from its adjacent teeth will be collected and adaptively fused for final classification. Children panoramic radiographs of 210 patients with one or more caries and 94 patients without caries are utilized, among which there are a total of 6028 teeth with 3039 to be caries. The proposed context aware CNN outperforms typical CNN baseline with the accuracy, precision, recall, F1 score, and area-under-the-curve (AUC) being 0.8272, 0.8538, 0.8770, 0.8652, and 0.9005, respectively, showing potential to improve typical CNN instead of just copying them in previous works. Specially, the proposed method performs better than two five-year attending doctors for the second primary molar caries diagnosis. Considering the results obtained, it is beneficial to promote CNN based deep learning methods for assisting dentists for caries diagnosis in hospitals.

Clinical and imaging features of melanotic neuro-ectodermal tumor of infancy of the maxillary bone: report of four cases and review of the literature.

Melanotic neuro-ectodermal tumor of infancy (MNTI) is an extremely rare tumor. The purpose of this study was to describe the imaging features of maxillary bone MNTIs and introduce the key points for clinical diagnosis of MNTI. We retrospectively reviewed four patients with histology-proven MNTIs arising from the maxillary bone. All patients underwent ultrasonic inspections, CT and/or MR scanning. Combined with previously literature, the imaging features were comprehensively evaluated and analyzed. All MNTIs showed a firm, non-ulcerated rapidly-growing soft-tissue swelling with pigmented (blue-colored or black-colored or gray-colored) mucosa. The onset ages were younger than 6 month-old. CT images showed osteolytic or expansive bone destruction of the involved maxillae, fragmentary cortical bone, "free-floating" tooth germs, with or without spiculated/sunburst periosteal reaction. The tumor appeared lightly hyper-intense on T2-weighted sequences, while isointense or lightly hypo-intense or lightly hyper-intense signal on T1-weighted sequences. Enhanced images all displayed heterogeneous enhancement. No metastasis features of lymph nodes or abdominal organs were demonstrated by cervical and abdominal ultrasonic inspections. As a conclusion, accurate recognition of the imaging features of MNTI combined with history and clinical manifestations (early infancy, painless, firm, pigmented mucosa, non-ulcerating lesion) can provide clues for diagnosis of this rare entity.

Midpalatal Suture CBCT Image Quantitive Characteristics Analysis Based on Machine Learning Algorithm Construction and Optimization.

BACKGROUND: Midpalatal suture maturation and ossification status is the basis for appraising maxillary transverse developmental status. METHODS: We established a midpalatal suture cone-beam computed tomography (CBCT) normalized database of the growth population, including 1006 CBCT files from 690 participants younger than 24 years old. The midpalatal suture region of interest (ROI) labeling was completed by two experienced clinical experts. The CBCT image fusion algorithm and image texture feature analysis algorithm were constructed and optimized. The age range prediction convolutional neural network (CNN) was conducted and tested. RESULTS: The midpalatal suture fusion images contain complete semantic information for appraising midpalatal suture maturation and ossification status during the fast growth and development period. Correlation and homogeneity are the two texture features with the strongest relevance to chronological age. The overall performance of the age range prediction CNN model is satisfactory, especially in the 4 to 10 years range and the 17 to 23 years range, while for the 13 to 14 years range, the model performance is compromised. CONCLUSIONS: The image fusion algorithm can help show the overall perspective of the midpalatal suture in one fused image effectively. Furthermore, clinical decisions for maxillary transverse deficiency should be appraised by midpalatal suture image features directly rather than by age, especially in the 13 to 14 years range.

In vivo methods for evaluating human midpalatal suture maturation and ossification: An updated review.

OBJECTIVES: The aim of this study was to perform an updated review of the in vivo methods to evaluate human midpalatal suture maturation and ossification, since this evaluation process remains an unsolved and critical problem in orthodontic treatment. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Scopus and Web of Science databases were searched up to November 30, 2021. Literature selection was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA, 2020 Edition) statement and was based on predetermined inclusion criteria. The overall and methodological characteristics of the selected studies were collected. The risk of bias was evaluated mainly through inter- and intra-evaluator agreement outcomes reported in each study. As there was a high heterogeneity among methodological studies, meta-analysis of the included studies was not applicable, and results were analysed descriptively. RESULTS: Nine articles met the inclusion criteria. Maxillary occlusal radiograph and computed tomography (CT), especially cone beam CT (CBCT), were reported. The occlusal radiograph is not adequate for evaluating the status of midpalatal suture maturation, and has been replaced by CBCT. Qualitative and quantitative CBCT evaluation methods provide limited evidence; however, opinions differ regarding the efficacy of these methods. CONCLUSIONS: For midpalatal suture maturation and ossification status evaluation, evidence for the current methods is still limited. Further methodological studies should use image information comprehensively and provide verification evidence on larger samples.

A Comprehensive Analysis of SE-lncRNA/mRNA Differential Expression Profiles During Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells.

Objective: Articular cartilage injury is common and difficult to treat clinically because of the characteristics of the cartilage. Bone marrow-derived mesenchymal stem cell (BMSC)-mediated cartilage regeneration is a promising therapy for treating articular cartilage injury. BMSC differentiation is controlled by numerous molecules and signaling pathways in the microenvironment at both the transcriptional and post-transcriptional levels. However, the possible function of super enhancer long non-coding RNAs (SE-lncRNAs) in the chondrogenic differentiation of BMSCs is still unclear. Our intention was to explore the expression profile of SE-lncRNAs and potential target genes regulated by SE-lncRNAs during chondrogenic differentiation in BMSCs. Materials and Methods: In this study, we conducted a human Super-Enhancer LncRNA Microarray to investigate the differential expression profile of SE-lncRNAs and mRNAs during chondrogenic differentiation of BMSCs. Subsequent bioinformatic analysis was performed to clarify the important signaling pathways, SE-lncRNAs, and mRNAs associated with SE-lncRNAs regulating the chondrogenic differentiation of BMSCs. Results: A total of 77 SE-lncRNAs were identified, of which 47 were upregulated and 30 were downregulated during chondrogenic differentiation. A total of 308 mRNAs were identified, of which 245 were upregulated and 63 were downregulated. Some pathways, such as focal adhesion, extracellular matrix (ECM)-receptor interaction, transforming growth factor-ß (TGF-ß) signaling pathway, and PI3K-Akt signaling pathway, were identified as the key pathways that may be implicated in the chondrogenic differentiation of BMSCs. Moreover, five potentially core regulatory mRNAs (PMEPA1, ENC1, TES, CDK6, and ADIRF) and 37 SE-lncRNAs in chondrogenic differentiation were identified by bioinformatic analysis. Conclusion: We assessed the differential expression levels of SE-lncRNAs and mRNAs, along with the chondrogenic differentiation of BMSCs. By analyzing the interactions and co-expression, we identified the core SE-lncRNAs and mRNAs acting as regulators of the chondrogenic differentiation potential of BMSCs. Our study also provided novel insights into the mechanism of BMSC chondrogenic and cartilage regeneration.

LncRNA, PLXDC2-OT promoted the osteogenesis potentials of MSCs by inhibiting the deacetylation function of RBM6/SIRT7 complex and OSX specific isoform.

Bone regeneration and remodeling are complex physiological processes that are regulated by key transcription factors. Understanding the regulatory mechanism of key transcription factors on the osteogenic differentiation of mesenchymal stem cells (MSCs) is a key issue for successful bone regeneration and remodeling. In the present study, we investigated the regulatory mechanism of the histone deacetylase Sirtuin 7 (SIRT7) on the key transcription factor OSX and osteogenesis of MSCs. In this study, we found that SIRT7 knockdown increased ALP activity and in vitro mineralization and promoted the expression of the osteogenic differentiation markers DSPP, DMP1, BSP, OCN, and the key transcription factor OSX in MSCs. In addition, SIRT7 could associate with RNA binding motif protein 6 (RBM6) to form a protein complex. Moreover, RBM6 inhibited ALP activity, the expression of DSPP, DMP1, BSP, OCN, and OSX in MSCs, and the osteogenesis of MSCs in vivo. Then, the SIRT7/RBM6 protein complex was shown to downregulate the level of H3K18Ac in the OSX promoter by recruiting SIRT7 to the OSX promoter and inhibiting the expression of OSX isoforms 1 and 2. Furthermore, lncRNA PLXDC2-OT could associate with the SIRT7/RBM6 protein complex to diminish its binding and deacetylation function in the OSX promoter and its inhibitory function on OSX isoforms 1 and 2 and to promote the osteogenic potential of MSCs.

SFRP2 enhances the osteogenic differentiation of apical papilla stem cells by antagonizing the canonical WNT pathway.

BACKGROUND: Exploring the molecular mechanisms underlying directed differentiation is helpful in the development of clinical applications of mesenchymal stem cells (MSCs). Our previous study on dental tissue-derived MSCs demonstrated that secreted frizzled-related protein 2 (SFRP2), a Wnt inhibitor, could enhance osteogenic differentiation in stem cells from the apical papilla (SCAPs). However, how SFRP2 promotes osteogenic differentiation of dental tissue-derived MSCs remains unclear. In this study, we used SCAPs to investigate the underlying mechanisms. METHODS: SCAPs were isolated from the apical papilla of immature third molars. Western blot and real-time RT-PCR were applied to detect the expression of ß-catenin and Wnt target genes. Alizarin Red staining, quantitative calcium analysis, transwell cultures and in vivo transplantation experiments were used to study the osteogenic differentiation potential of SCAPs. RESULTS: SFRP2 inhibited canonical Wnt signaling by enhancing phosphorylation and decreasing the expression of nuclear ß-catenin in vitro and in vivo. In addition, the target genes of the Wnt signaling pathway, AXIN2 (axin-related protein 2) and MMP7 (matrix metalloproteinase-7), were downregulated by SFRP2. WNT1 inhibited the osteogenic differentiation potential of SCAPs. SFRP2 could rescue this WNT1-impaired osteogenic differentiation potential. CONCLUSIONS: The results suggest that SFRP2 could bind to locally present Wnt ligands and alter the balance of intracellular Wnt signaling to antagonize the canonical Wnt pathway in SCAPs. This elucidates the molecular mechanism underlying the SFRP2-mediated directed differentiation of SCAPs and indicates potential target genes for improving dental tissue regeneration.

SFRP2 enhanced the adipogenic and neuronal differentiation potentials of stem cells from apical papilla.

Dental tissue-derived mesenchymal stem cells (MSCs) are easily obtained and considered as a favorable cell source for tissue engineering, but the regulation of direct differentiation is unknown, which restricts their application. The present study investigated the effect of SFRP2, a Wnt signaling modulator, on MSC differentiation using stem cells from apical papilla (SCAPs). The cells were cultured in specific inducing medium for adipogenic, neurogenic, or chondrogenic differentiation. Over-expression of SFRP2 via retroviral infection enhanced the adipogenic and neurogenic differentiation of SCAPs. While inhibit of Wnt pathway by IWR1-endo could enhance the neurogenic differentiation potentials of SCAPs, similar with the function of SFRP2. In addition, over-expression of SFRP2 up-regulated the expression of stemness-related genes SOX2 and OCT4. Furthermore, SOX2 and OCT4 expression was significantly inhibited after lentiviral silencing of SFRP2 in SCAPs. Therefore, our results suggest that SFRP2 enhances the adipogenic and neurogenic differentiation potentials of SCAPs by up-regulating SOX2 and OCT4. Moreover, the effect of SFRP2 in neurogenic differentiation of SCAPs maybe also associated with Wnt inhibition. Our results provided useful information about the molecular mechanism underlying directed differentiation in dental tissue-derived MSCs.

Demethylation of SFRP2 by histone demethylase KDM2A regulated osteo-/dentinogenic differentiation of stem cells of the apical papilla.

OBJECTIVES: Dental mesenchymal stem cells (MSCs) are easily obtained; however, mechanisms underlying directed differentiation of these cells remains unclear. Wnt/ß-catenin signalling is essential for mesenchymal cell commitment and differentiation, and Wnt inhibition is linked to stem cell maintenance and function. Secreted frizzled-related protein 2 (SFRP2) competes with the Frizzled receptor for direct binding to Wnt and blocks activation of Wnt signalling. Here, we used stem cells derived from apical papillae (SCAPs) to study the functions of SFRP2. MATERIALS AND METHODS: SCAPs were isolated from apical papillae of immature third molars. The cells were analysed using alkaline phosphatase activity assays, Alizarin red staining and quantitative calcium measurements. In addition, we evaluated expression profile of genes associated with osteogenesis and dentinogenesis (osteo-/dentinogenesis), and conducted in vivo transplantation experiments to determine osteo-/dentinogenic differentiation potential of SCAPs. ChIP assays were used to detect histone methylation at the SFRP2 promoter. RESULTS: We found that SFRP2 enhanced osteo-/dentinogenic differentiation via Osterix, a key transcription factor in SCAPs. Furthermore, silencing SFRP2 induced SCAP cell death in osteogenic-inducing medium, indicating that SFRP2 is a key factor in maintaining SCAP survival following osteo-/dentinogenic commitment. Moreover, we found that silencing KDM2A, a histone demethylase and BCL6 co-repressor, de-repressed SFRP2 transcription by increasing histone H3K4 and H3K36 methylation at the SFRP2 promoter. CONCLUSIONS: Our results have identified a new function of SFRP2 and shed new light on the molecular mechanism underlying directed differentiation of stem cells of dental origin.