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1.
Hum Genomics ; 17(1): 93, 2023 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-37833774

RESUMEN

BACKGROUND: Tooth agenesis is a common dental anomaly that can substantially affect both the ability to chew and the esthetic appearance of patients. This study aims to identify possible genetic factors that underlie various forms of tooth agenesis and to investigate the possible molecular mechanisms through which human dental pulp stem cells may play a role in this condition. RESULTS: Using whole-exome sequencing of a Han Chinese family with non-syndromic tooth agenesis, a rare mutation in FGFR1 (NM_001174063.2: c.103G > A, p.Gly35Arg) was identified as causative and confirmed by Sanger sequencing. Via GeneMatcher, another family with a known variant (NM_001174063.2: c.1859G > A, p.Arg620Gln) was identified and diagnosed with tooth agenesis and a rare genetic disorder with considerable intrafamilial variability. Fgfr1 is enriched in the ectoderm during early embryonic development of mice and showed sustained low expression during normal embryonic development of Xenopus laevis frogs. Functional studies of the highly conserved missense variant c.103G > A showed deleterious effects. FGFR1 (c.103G > A) was overexpressed compared to wildtype and promoted proliferation while inhibiting apoptosis in HEK293 and human dental pulp stem cells. Moreover, the c.103G > A variant was found to suppress the epithelial-mesenchymal transition. The variant could downregulate ID4 expression and deactivate the TGF-beta signaling pathway by promoting the expression of SMAD6 and SMAD7. CONCLUSION: Our research broadens the mutation spectrum associated with tooth agenesis and enhances understanding of the underlying disease mechanisms of this condition.


Asunto(s)
Anodoncia , Humanos , Células HEK293 , Anodoncia/genética , Mutación , Mutación Missense/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética
2.
BMC Oral Health ; 24(1): 1173, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39363251

RESUMEN

BACKGROUND: This study aimed to investigate the facial soft tissue characteristics of patients with different types of malocclusion. METHODS: The 3dMD scanning data of patients with malocclusion admitted to our hospital from January 2018 to April 2022 were analyzed retrospectively. Forty-seven patients with Class I malocclusion, 43 patients with Class II malocclusion and 44 patients with Class III malocclusion were selected. All patients underwent 3dMD scans prior to orthodontic treatment. Then the differences in the 3D morphological parameters of the facial soft tissues were compared between different sexes and different types of malocclusion. Spearman's correlation was further used to analyze the correlation between each parameter and the classification of malocclusion. RESULTS: In the Class I group and Class II group, there were no significant differences in the 3D morphometric parameters of malocclusion patients of different sexes (P > 0.05). There were significant differences between Al (R)-AL (L), Ac (R)-Ac (L), Prn-Ac (L), n-Prn-Sn, and Al (R)-Al (L)/Ac (L)-Ah (L) values among the three groups of patients. Spearman correlation analysis showed that Ac (R)-Ac (L) and Al (R)-Al (L)/Ac (R)-Ac (L) were correlated with the type of malocclusion. CONCLUSION: Differences in facial soft tissues exist in patients with Class I, II, and III malocclusion. 3dMD technique may be helpful in developing an effective treatment plan prior to orthodontic treatment.


Asunto(s)
Cara , Maloclusión , Humanos , Masculino , Femenino , Cara/anatomía & histología , Cara/diagnóstico por imagen , Estudios Retrospectivos , Maloclusión/clasificación , Maloclusión/diagnóstico por imagen , Maloclusión/patología , Adolescente , Imagenología Tridimensional/métodos , Adulto Joven , Factores Sexuales , Adulto , Maloclusión de Angle Clase III/diagnóstico por imagen , Maloclusión de Angle Clase III/patología , Maloclusión Clase II de Angle/diagnóstico por imagen , Maloclusión Clase II de Angle/patología , Maloclusión Clase II de Angle/terapia
3.
Oral Dis ; 29(6): 2423-2437, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36350305

RESUMEN

Non-syndromic skeletal Class III malocclusion is a major craniofacial disorder characterized by genetic and environmental factors. Patients with severe skeletal Class III malocclusion require orthognathic surgery to obtain aesthetic facial appearance and functional occlusion. Recent studies have demonstrated that susceptible chromosomal regions and genetic variants of candidate genes play important roles in the etiology of skeletal Class III malocclusion. Here, we provide a comprehensive review of our current understanding of the genetic factors that affect non-syndromic skeletal Class III malocclusion, including the patterns of inheritance and multiple genetic approaches. We then summarize the functional studies on related loci and genes using cell biology and animal models, which will help to implement individualized therapeutic interventions.


Asunto(s)
Maloclusión de Angle Clase III , Maloclusión , Humanos , Estética Dental , Maloclusión de Angle Clase III/genética , Maloclusión de Angle Clase III/cirugía , Maloclusión/complicaciones , Cefalometría/efectos adversos
4.
Oral Dis ; 29(3): 1102-1114, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34878701

RESUMEN

OBJECTIVE: Premolar agenesis is a common subtype of tooth agenesis. Although a genome-wide study (GWAS) has identified some variants involved in tooth agenesis in Europeans, the genetic mutation related to premolar agenesis in the Chinese population remains unclear. MATERIALS AND METHODS: We present a GWAS in 218 premolar agenesis cases and 1,222 controls using the Illumina Infinium® Global Screening Array. 5,585,618 single nucleotide polymorphisms (SNPs) were used for tests of associations with premolar agenesis. RESULTS: Four independent SNPs on chromosome 2 were identified as susceptibility loci, including rs147680216, rs79743039, rs60540881, and rs6738629. The genome-wide significant SNP rs147680216 (p = 6.09 × 10-9 ) was predicted to change the structure of the WNT10A protein and interact with hedgehog signaling pathway components. Meta-analysis showed that the rs147680216 A allele significantly increased the risk of tooth agenesis (p = 0.000). The other three SNPs with nominal significance are novel susceptibility loci. Of them, rs6738629 (p = 5.40 × 10-6 ) acts as a potential transcriptional regulator of GCC2, a gene playing a putative role in dental and craniofacial development. CONCLUSION: Our GWAS indicates that rs147680216 and additional three novel susceptibility loci on chromosome 2 are associated with the risk of premolar agenesis in the Chinese population.


Asunto(s)
Anodoncia , Estudio de Asociación del Genoma Completo , Humanos , Diente Premolar , Pueblos del Este de Asia , Proteínas Hedgehog/genética , Anodoncia/genética , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad
5.
Clin Oral Investig ; 28(1): 29, 2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38147163

RESUMEN

OBJECTIVES: Three distinct models were utilized to investigate the combined impacts of serum aldehyde exposure and periodontitis. MATERIALS AND METHODS: We performed a cross-sectional analysis using data from 525 participants in the 2013-2014 National Health and Nutrition Examination Survey (NHANES). The directed acyclic graphs (DAG) were used to select a minimal sufficient adjustment set of variables (MSAs). To investigate the relationship between aldehydes and periodontitis, we established three models including multiple logistic regression model, restricted cubic spline (RCS) model, and Bayesian kernel machine regression (BKMR) model. RESULTS: After taking all covariates into account, the multiple logistic regression model revealed that elevated concentrations of isopentanaldehyde and propanaldehyde were strongly associated with periodontitis (isopentanaldehyde: OR: 2.38, 95% CI: 1.34-4.23; propanaldehyde: OR: 1.51, 95% CI: 1.08-2.13). Furthermore, the third tertile concentration of isopentanaldehyde was associated with a 2.04-fold increase in the incidence of periodontitis (95% CI: 1.05-3.95) compared to the first tertile concentration, with a P for trend = 0.04. RCS models showed an "L"-shaped relationship between isopentanaldehyde and periodontitis (P for nonlinear association < 0.01), with inflection point of 0.43 ng/mL. BKMR identified a strong connection between mixed aldehydes and periodontitis, with isopentanaldehyde exhibiting the greatest posterior inclusion probability (PIP) with 0.901 and propanaldehyde exhibiting a PIP with 0.775. CONCLUSIONS: Isopentanaldehyde and propanaldehyde are positively associated with the risk of periodontitis. CLINICAL RELEVANCE: Periodontitis may be associated with exposure to mixed aldehyde. This study emphasizes the important role of aldehydes in primary prevention of periodontitis.


Asunto(s)
Aldehídos , Periodontitis , Humanos , Teorema de Bayes , Estudios Transversales , Encuestas Nutricionales , Aldehídos/efectos adversos , Periodontitis/epidemiología
6.
Am J Orthod Dentofacial Orthop ; 163(4): 509-519, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37079283

RESUMEN

INTRODUCTION: This retrospective clinical study investigated the clinical changes of maxillary central incisor and alveolar bone in Class II Division 2 nonextraction treatment with fixed appliances or clear aligners on the basis of cone-beam computed tomography. METHODS: Fifty-nine Chinese Han patients with similar demographic characteristics were collected from a conventional bracket group, a self-ligating bracket group, and a clear aligner group. All measurements about root resorption and alveolar bone thickness on the cone-beam computed tomography images were tested. Changes between pretreatment and posttreatment were evaluated by paired-sample t test. The variation among the 3 groups was compared by 1-way analysis of variance. RESULTS: The resistance center of the maxillary central incisor showed upward or forward movement, and the axial inclination was increased in 3 groups (P <0.0001). Root volume loss in the clear aligner group (23.68 ± 4.82 mm3) was significantly less than that in the fixed appliances group (28.24 ± 6.44 mm3 in the conventional bracket group, 28.17 ± 6.07 mm3 in the self-ligating bracket group) (P <0.05). All 3 groups showed a significant decrease in palatal alveolar bone and total bone thickness at all 3 levels at posttreatment. In contrast, labial bone thickness significantly increased except for crestal level l. Among the 3 groups, the clear aligner group had a prominent increase in labial bone thickness at the apical level (P = 0.0235). CONCLUSIONS: Clear aligner treatment for Class II Division 2 malocclusions could effectively reduce the incidence of fenestration and root resorption. Our findings will be beneficial to comprehensively understand the effectiveness of different appliances for Class II Division 2 malocclusions treatment.


Asunto(s)
Maloclusión Clase II de Angle , Aparatos Ortodóncicos Removibles , Resorción Radicular , Humanos , Incisivo/diagnóstico por imagen , Estudios Retrospectivos , Maloclusión Clase II de Angle/diagnóstico por imagen , Maloclusión Clase II de Angle/terapia , Aparatos Ortodóncicos Fijos , Tomografía Computarizada de Haz Cónico , Maxilar/diagnóstico por imagen
7.
Int J Mol Sci ; 23(18)2022 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-36142585

RESUMEN

Skeletal Class III malocclusion with maxillary deficiency is a severe maxillofacial disease with unclear pathogenic mechanisms. We recruited a Han Chinese family who was clinically diagnosed with skeletal Class III malocclusion and maxillary deficiency. Using whole exome sequencing, a missense variant in ADAMTS2 (NM_014244: c.3506G>T: p.G1169V) was identified and predicted as deleterious by in silico tools. We also found ADAMTS2 variants associated with deficient maxillary development in a cohort. ADAMTS2 expression in HEK293 cells showed significant decrease due to the variant, which was also consistent in dental pulp stem cells from the proband and a healthy control. In the adamts2-knockdown zebrafish model, the length and width of the ethmoid plate, as well as the length of the palatoquadrate became significantly shorter than the control group (p < 0.001), while there was no significant difference in the length and width of the mandible. The expression of Sox3, which was required in early embryonic craniofacial development, was significantly downregulated in the adamts2-knockdown zebrafish embryos. Bioinformatic and cellular studies showed that the decreased expression of ADAMTS2 may inhibit downstream ErbB signaling pathway transduction and restrain subsequent osteogenesis in human adult mesenchymal stromal cells. Collectively, these data showed that ADAMTS2 (c.3506G>T: p.G1169V) may confer susceptibility to risk of skeletal Class III malocclusion with maxillary deficiency.


Asunto(s)
Maloclusión de Angle Clase III , Pez Cebra , Proteínas ADAMTS/genética , Adulto , Animales , Células HEK293 , Humanos , Maloclusión de Angle Clase III/patología , Mandíbula , Maxilar/patología , Pez Cebra/genética
8.
Cleft Palate Craniofac J ; 59(11): 1352-1360, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-34524929

RESUMEN

To investigate the longitudinal influence of alveolar bone grafting on the oral microbiota of children with cleft lip and palate (CLP).Twenty-eight children with nonsyndromic CLP were recruited and underwent secondary alveolar bone grafting at the first time. Unstimulated saliva and plaque samples were collected from the subjects preoperatively and at 2 days, 1 month, and 3 months postoperatively. The v3-v4 hypervariable regions of the 16S rRNA gene from bacterial DNA were sequenced using the Illumina MiSeq sequencing platform.The alpha diversity of the saliva and plaque microbiota was significantly decreased at 2 days postoperatively and then increased at 1 and 3 months postoperatively. The saliva and plaque microbiota compositions at 2 days postoperatively differed from those at the other time points, and the microbiota compositions at 1 and 3 months postoperatively showed a gradual shift toward the preoperative composition. The saliva, but not plaque, microbiota composition 3 months postoperatively was similar to that preoperatively.The effect of secondary alveolar bone grafting on the plaque microbiota in children with CLP lasted longer than the saliva microbiota. Alveolar bone grafting altered the saliva microbiota in children with CLP within 3 months postoperatively.


Asunto(s)
Injerto de Hueso Alveolar , Labio Leporino , Fisura del Paladar , Placa Dental , Microbiota , Trasplante Óseo , Niño , Labio Leporino/cirugía , Fisura del Paladar/cirugía , ADN Bacteriano , Humanos , ARN Ribosómico 16S/genética
9.
IUBMB Life ; 73(1): 213-222, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33249758

RESUMEN

Diabetes mellitus (DM)-induced glucolipotoxicity is a factor strongly contributing to alveolar bone deficiency. Parathyroid hormone (PTH) has been identified as a main systemic mediator to balance physiological calcium in bone. This study aimed to uncover PTH's potential role in ameliorating the osteogenic capacity of human bone marrow mesenchymal stem cells (HBMSCs) against glucolipotoxicity. Optimal PTH concentrations and high glucose and palmitic acid (GP) were administered to cells, followed by alkaline phosphatase (ALP) staining and ALP activity assay. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and Immunoblot were carried out for assessing mRNA and protein amounts, respectively. Cell counting kit-8 (CCK-8) and flow cytometry were performed for quantitating cell proliferation. Osteogenesis and oxidative stress were determined, and the involvement of mitogen-activated protein kinase (MAPK) signaling was further verified. About 1-50 mmol/ml GP significantly inhibited the osteogenic differentiation of HBMSCs. 10-9 mol/L PTH was found to be the optimal concentration for HBMSC induction. PTH had no effects on HBMSC proliferation, with or without GP treatment. PTH reversed inadequate osteogenesis and excessive oxidative stress in GP-treated HBMSCs. Mechanistically, PTH activated p38 MAPK signaling, while inhibiting p38 MAPK-suppressed PTH's beneficial impacts on HBMSCs. Collectively, PTH promotes osteogenic differentiation in HBMSCs against glucolipotoxicity via p38 MAPK signaling.


Asunto(s)
Glucosa/efectos adversos , Células Madre Mesenquimatosas/citología , Osteogénesis , Ácido Palmítico/efectos adversos , Hormona Paratiroidea/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Adulto , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Inhibidores Enzimáticos/efectos adversos , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Transducción de Señal , Edulcorantes/efectos adversos , Adulto Joven , Proteínas Quinasas p38 Activadas por Mitógenos/genética
10.
Oral Dis ; 27(7): 1747-1754, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33128317

RESUMEN

OBJECTIVE: To explore susceptibility genes and pathways for non-syndromic cleft lip with or without cleft palate (NSCL/P). MATERIALS AND METHODS: Two genome-wide association studies (GWAS) datasets, including 858 NSCL/P cases and 1,248 controls, were integrated with expression quantitative trait loci (eQTL) dataset identified by Genotype-Tissue Expression (GTEx) project in whole-blood samples. The expression of the candidate genes in mouse orofacial development was inquired from FaceBase. Protein-protein interaction (PPI) network was visualized to identify protein functions. Go and KEGG pathway analyses were performed to explore the underlying risk pathways. RESULTS: A total of 233 eQTL single-nucleotide polymorphisms (SNPs) in 432 candidate genes were identified to be associated with the risk of NSCL/P. One hundred and eighty-three susceptible genes were expressed in mouse orofacial development according to FaceBase. PPI network analysis highlighted that these genes involved in ubiquitin-mediated proteolysis (KCTD7, ASB1, UBOX5, ANAPC4) and DNA synthesis (XRCC3, RFC3, KAT5, RHNO1) were associated with the risk of NSCL/P. GO and KEGG pathway analyses revealed that the fatty acid metabolism pathway (ACADL, HSD17B12, ACSL5, PPT1, MCAT) played an important role in the development of NSCL/P. CONCLUSIONS: Our results identified novel susceptibility genes and pathways associated with the development of NSCL/P.


Asunto(s)
Labio Leporino , Fisura del Paladar , 17-Hidroxiesteroide Deshidrogenasas , Animales , Estudios de Casos y Controles , Labio Leporino/genética , Fisura del Paladar/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Ratones , Polimorfismo de Nucleótido Simple , Canales de Potasio , Sitios de Carácter Cuantitativo/genética , Proteínas Supresoras de la Señalización de Citocinas
11.
J Craniofac Surg ; 32(2): 496-499, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33704968

RESUMEN

OBJECTIVE: This study aims to investigate nasal morphologies associated with nasal airway obstruction in unilateral alveolar cleft patients. METHODS: A total of 234 unilateral alveolar cleft cases were performed cone beam computed tomography scans. The digital imaging and communication in medicine data were imported into Simplant Pro software. The radiographic features including nasal septum deviation and inferior turbinate hypertrophy as well as nasal airway volume and sinusitis were analyzed. RESULTS: A new radiographic classification of relationship between nasal septum and inferior turbinate (NS-IT) on the cleft side was proposed and three types of NS-IT relationship (type I, II and III) were identified in 234 cases. The statistical analysis revealed that the nasal airway volume on non-cleft side was significantly higher than that on cleft side in each of three types (P  < 0.0001), while no difference of nasal airway volume on non-cleft side was found among three types. In addition, the nasal airway volume on non-cleft side in type I and II was significantly higher than that in type III (P < 0.0001). Also, type III presented higher rate of maxillary sinusitis (P = 0.0154) and ethmoid sinusitis on cleft side (P = 0.0490) than type I and II. The other indexes including clinical variances were not significant among three types. CONCLUSIONS: Unilateral alveolar cleft patients with type III NS-IT relationship could have nasal airway obstruction and higher rate of maxillary and ethmoid sinusitis on cleft side, which may be taken into account at primary cleft repair and alveolar bone grafting treatment.


Asunto(s)
Labio Leporino , Fisura del Paladar , Obstrucción Nasal , Fisura del Paladar/complicaciones , Fisura del Paladar/diagnóstico por imagen , Humanos , Obstrucción Nasal/diagnóstico por imagen , Obstrucción Nasal/etiología , Tabique Nasal , Cornetes Nasales/diagnóstico por imagen
12.
J Cell Mol Med ; 24(23): 13669-13678, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33108691

RESUMEN

Although several genome-wide association studies (GWAS) of non-syndromic cleft lip with or without cleft palate (NSCL/P) have been reported, more novel association signals are remained to be exploited. Here, we performed an in-depth analysis of our previously published Chinese GWAS cohort study with replication in an extra dbGaP case-parent trios and another in-house Nanjing cohort, and finally identified five novel significant association signals (rs11119445: 3' of SERTAD4, P = 6.44 × 10-14 ; rs227227 and rs12561877: intron of SYT14, P = 5.02 × 10-13 and 2.80 × 10-11 , respectively; rs643118: intron of TRAF3IP3, P = 4.45 × 10-6 ; rs2095293: intron of NR6A1, P = 2.98 × 10-5 ). The mean (standard deviation) of the weighted genetic risk score (wGRS) from these SNPs was 1.83 (0.65) for NSCL/P cases and 1.58 (0.68) for controls, respectively (P = 2.67 × 10-16 ). Rs643118 was identified as a shared susceptible factor of NSCL/P among Asians and Europeans, while rs227227 may contribute to the risk of NSCL/P as well as NSCPO. In addition, sertad4 knockdown zebrafish models resulted in down-regulation of sox2 and caused oedema around the heart and mandibular deficiency, compared with control embryos. Taken together, this study has improved our understanding of the genetic susceptibility to NSCL/P and provided further clues to its aetiology in the Chinese population.


Asunto(s)
Labio Leporino/diagnóstico , Labio Leporino/genética , Fisura del Paladar/diagnóstico , Fisura del Paladar/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Sitios de Carácter Cuantitativo , Alelos , Animales , Estudios de Casos y Controles , Biología Computacional/métodos , Modelos Animales de Enfermedad , Femenino , Edición Génica , Estudios de Asociación Genética/métodos , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Masculino , Anotación de Secuencia Molecular , Oportunidad Relativa , Fenotipo , Polimorfismo de Nucleótido Simple , Pez Cebra
13.
J Cell Physiol ; 235(9): 5972-5984, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-31970784

RESUMEN

Mechanical force across sutures is able to promote suture osteogenesis. Orthodontic clinics often use this biological characteristic of sutures to treat congenital cranio-maxillofacial malformations. However, the underlying mechanisms still remain poorly understood. Craniofacial sutures provide a special growth source and support primary sites of osteogenesis. Here, we isolated rat sagittal suture cells (rSAGs), which had mesenchymal stem cell characteristics and differentiating abilities. Cells were then subjected to mechanical tension (5% elongation, 0.5 Hz; sinusoidal waveforms) showing that mechanical tension could enhance osteogenic differentiation but hardly affect proliferation of rSAGs. Besides, mechanical tension could increase Rho-associated kinase (ROCK) expression and enhance transcriptional coactivator with PDZ-binding motif (TAZ) nuclear translocation. Inhibiting ROCK expression could suppress tension-induced osteogenesis and block tension-induced upregulation of nuclear TAZ. In addition, our results indicated that TAZ had direct combination sites with runt-related transcription factor 2 (Runx2) in rSAGs, and knock-downed TAZ simultaneously decreased the expression of Runx2 no matter with or without mechanical tension. In summary, our findings demonstrated that the multipotency of rSAGs in vitro could give rise to early osteogenic differentiation under mechanical tension, which was mediated by ROCK-TAZ signal axis.


Asunto(s)
Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Suturas Craneales/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Osteogénesis/genética , Transactivadores/genética , Quinasas Asociadas a rho/genética , Animales , Diferenciación Celular/genética , Suturas Craneales/crecimiento & desarrollo , Suturas Craneales/patología , Fenómenos Mecánicos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratas , Transducción de Señal/genética , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ
14.
IUBMB Life ; 72(2): 296-304, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31509344

RESUMEN

Human adipose-derived stem cells (HASCs) represent pluripotent cells capable of differentiating into the bone tissue. Meanwhile, human amnion-derived mesenchymal stem cells (HAMSCs) could cause mesenchymal stem cells to differentiate into the bone tissue. This work assessed the osteogenic effects exerted by HAMSCs on the potential of HASCs to form bone cells. Cell growth was evaluated flow-cytometrically. Differentiation into osteoblasts and mineral formation were assessed by chromogenic alkaline phosphatase activity substrate assay and Alizarin red S staining. Adiponectin (APN), the adipocytokine secreted by adipocytes, was evaluated by enzyme-linked immunosorbent assay. In this study, HAMSCs concentration-dependently induced growth, osteoblastic differentiation, and APN excretion in HASCs. Mechanistically, immunofluorescence and immunoblot revealed HAMSCs promoted cytosolic translocation of leucine zipper motif (APPL1) from the nucleus and induced extracellular signaling-regulated kinase 1/2 (ERK1/2) phosphorylation in HASCs. Furthermore, HAMSC effects were markedly blunted by pretreatment with APPL1 siRNA and U0126, an ERK1/2 signaling inhibitor with high selectivity. These results suggested that APN excretion is not suppressed by APPL1 knockdown in HASCs, but by ERK1/2 inhibition. These findings collectively indicate that HAMSCs induce the osteogenesis of HASCs by promoting APN excretion through APPL1-ERK1/2 activation.


Asunto(s)
Adiponectina/metabolismo , Tejido Adiposo/citología , Amnios/citología , Diferenciación Celular , Células Madre Mesenquimatosas/citología , Osteoblastos/citología , Células Madre/citología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Tejido Adiposo/metabolismo , Amnios/metabolismo , Células Cultivadas , Humanos , Células Madre Mesenquimatosas/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Osteoblastos/metabolismo , Fosforilación , Transducción de Señal , Células Madre/metabolismo
15.
Arch Biochem Biophys ; 694: 108594, 2020 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-32979390

RESUMEN

Osteocytes sense extracellular mechanical stimuli and transduce them into biochemical signals to regulate bone remodeling. The function is also evidenced in orthodontic tooth movement. But the underlying mechanisms haven't been clarified. Autophagy is an evolutionarily conserved cellular catabolic process which affects cellular secretory capabilities. We hypothesized that mechanical force activated osteocyte autophagy through TFE3-related signaling and further promoted osteocyte-mediated osteoclastogenesis. In the present study, we demonstrated that osteocyte autophagy was activated under mechanical compressive force using murine orthodontic tooth movement model since the number of LC3B-positive osteocytes increased by 3-fold in the compression side. In addition, both in vitro mechanical compression and chemical autophagy agonist increased the secretion of RANKL in osteocytes by 3-fold and 4-fold respectively, which is a crucial cytokine for osteoclastogenesis. Lastly, conditioned medium collected from compressed osteocytes promoted the development of osteoclasts. These results suggest that osteocytes could promote osteoclastogenesis via autophagy-mediated RANKL secretion under mechanical compressive force. Our research might provide evidence for exploring methods to accelerate tooth movement in clinic.


Asunto(s)
Autofagia/fisiología , Osteocitos/metabolismo , Osteogénesis/fisiología , Ligando RANK/metabolismo , Animales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Línea Celular , Masculino , Ratones , Ratones Endogámicos C57BL , Transducción de Señal/fisiología , Estrés Mecánico , Técnicas de Movimiento Dental
16.
J Craniofac Surg ; 31(6): 1629-1632, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32796297

RESUMEN

OBJECTIVES: This study aimed to compare the anatomical features of alveolar cleft in patients with complete unilateral cleft lip and palate (UCLP) of different ages. METHODS: Sixty UCLP patients were divided into 3 groups as follows: group 1 (7-12 years old), group 2 (13-18 years old) and group 3 (more than 18 years old). The radiographic images were analyzed based on cone beam computed tomography (CBCT) images. RESULTS: The mean age in 3 groups was 10.45 ±â€Š1.15, 15.05 ±â€Š1.90, and 22.55 ±â€Š3.00 years (P < 0.0001). The lip-palatal width in Group 2 and 3 was 15.14 ±â€Š3.67 mm and 15.50 ±â€Š3.92 mm, which was significantly larger than 12.97 ±â€Š1.82 mm in Group 1 (P = 0.037). The volume of alveolar defect was 1.09 ±â€Š0.23 cm, 1.28 ±â€Š0.38 cm and 1.40 ±â€Š0.58 cm in 3 groups, and the difference between any 2 of them was significant (P = 0.0004). The prevalence of ipsilateral but contralateral maxillary sinusitis was significant among 3 groups (P = 0.0015) while the other nasal deformities including nasal septum deviation and inferior turbinate hypertrophy was not found significant. CONCLUSIONS: Alveolar cleft volume increased with age, which is properly due to enlarged width of lip-palatal defect. The significant higher frequencies of ipsilateral maxillary sinusitis in patients under 18 could increase the risk of bone infection.


Asunto(s)
Labio Leporino/diagnóstico por imagen , Fisura del Paladar/diagnóstico por imagen , Adolescente , Adulto , Niño , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Tomografía Computarizada de Haz Cónico , Femenino , Humanos , Labio , Masculino , Tabique Nasal , Adulto Joven
17.
Hum Mutat ; 40(11): 2057-2067, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31283072

RESUMEN

Nonsyndromic cleft lip with/without cleft palate (NSCL/P) is one of the most common human congenital defects. Rs2262251 (G>C) in long noncoding RNA (lncRNA) RP11-462G12.2 is in high linkage disequilibrium with rs8049367, which was identified in our previous genome-wide association study on NSCL/P, and is a potential causative single-nucleotide polymorphism (SNP) for NSCL/P. To test these hypotheses, rs2262251 was evaluated in another cohort of 1,314 cases and 1,259 controls. Rs2262251 was associated with NSCL/P risk (p = .003). However, no association was detected for cleft palate only. SNP rs2262251 affected the structure and expression of lncRNA RP11-462G12.2 in HEK293 and HEPM cells and in lip tissues from patients with NSCL/P. Overexpression of the rs2262251 G allele contributed to reducing the number of cells in the G0/G1 phase, inhibiting cell apoptosis, and promoting cell proliferation in vitro. The rs2262251 C allele regulated the expression of miR-744-5p and its target gene IQSEC2, both of which were expressed in human lip tissues, and showed reverse correlation during mouse lip development. Taken together, these findings suggest that rs2262251 is associated with the risk of NSCL/P and participates in a lncRNA-miRNA-mRNA regulatory axis in which miR-744-5p and IQSEC2 combine to control NSCL/P development.


Asunto(s)
Alelos , Labio Leporino/genética , Fisura del Paladar/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Fenotipo , ARN Largo no Codificante/genética , Sustitución de Aminoácidos , Labio Leporino/diagnóstico , Fisura del Paladar/diagnóstico , Células HEK293 , Humanos
18.
Oral Dis ; 25(7): 1751-1758, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31233659

RESUMEN

BACKGROUND: Non-syndromic supernumerary teeth (NSST) or hyperdontia may share common genetic determinants with non-syndromic cleft lip with or without palate (NSCL/P). The aim of this study was to test the associations between five genome-wide-associated NSCL/P-susceptible single nucleotide polymorphisms (SNPs) (rs2235371, rs7078160, rs8049367, rs4791774, and rs13041247) and the occurrence of NSST. MATERIALS AND METHODS: A total of 163 cases and 326 controls were recruited and their genomic DNA was extracted from blood samples. Five NSCL/P-susceptible SNPs (rs2235371, rs7078160, rs8049367, rs4791774, and rs13041247) were genotyped by TaqMan method. Odds ratio (OR) and 95% confidence interval (CI) were used to estimate the associations between the SNPs and the risk of NSST by PLINK software. RESULTS: Rs4791774 (A > G) and rs13041247 (T > C) were associated with risk of NSST (rs4791774: Padd  = 0.011, OR, 95% CI = 0.62, 0.43-0.90; rs13041247: Phomo  = 0.031, OR, 95% CI = 1.79, 1.05-3.05) and one supernumerary tooth (rs4791774: Pdom  = 0.009, OR, 95% CI = 0.56, 0.36-0.87; rs13041247: Phomo  = 0.034, OR, 95% CI = 1.82, 1.05-3.15). Rs4791774 (A > G) was also showed association with risk of upper arch supernumerary teeth only (Padd  = 0.010, OR, 95% CI = 0.60, 0.41-0.89). CONCLUSION: Non-syndromic cleft lip with or without palate-susceptible loci rs4791774 (A > G) and rs13041247 (T > C) were associated with the risk of supernumerary teeth.


Asunto(s)
Labio Leporino/genética , Fisura del Paladar/genética , Polimorfismo de Nucleótido Simple/genética , Diente Supernumerario/genética , Adolescente , Pueblo Asiatico , Estudios de Casos y Controles , Niño , China , Labio Leporino/complicaciones , Fisura del Paladar/complicaciones , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Diente Supernumerario/complicaciones
19.
Oral Dis ; 25(3): 803-811, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30578605

RESUMEN

OBJECTIVE: Non-syndromic tooth agenesis (NSTA) may share common genetic factors with non-syndromic cleft lip with or without cleft palate (NSCL/P). Single-nucleotide polymorphisms (SNPs) were associated with individual's susceptibility to these anomalies. We selected five NSCL/P-associated SNPs from our previous genome-wide association study (GWAS) to test for the associations with NSTA. MATERIALS AND METHODS: A total of 677 NSTA cases and 1,144 healthy controls were recruited in this case-control study. Five genome-wide NSCL/P-associated SNPs (rs2235371, rs7078160, rs8049367, rs4791774, and rs13041247) were genotyped by TaqMan platform and evaluated for the associations with NSTA using plink software. RESULTS: No significant associations between these SNPs and risk of NSTA were observed in the overall analysis and subgroup analysis with the number of missing teeth. However, in the subgroup analysis by tooth position, rs8049367 was nominally associated with mandibular premolar agenesis (Dominant model: ORdom  = 0.66, 95% CIdom  = 0.47-0.93, pdom  = 0.016; Heterozygote model: ORhet  = 0.60, 95% CIhet  = 0.41-0.88, Phet  = 0.008). Rs4791774 showed a nominal association with congenitally missing maxillary canine (Dominant model: ORdom  = 0.53, 95% CIdom  = 0.28-0.98, pdom  = 0.041; Heterozygote model: ORhet  = 0.50, 95% CIhet  = 0.26-0.97, Phet  = 0.041) and premolar (Additive model: OR = 0.59, 95% CI = 0.36-0.96, p = 0.035). CONCLUSION: This study showed that NSCL/P susceptible loci rs8049367 and rs4791774 were probably associated with the risk of NSTA.


Asunto(s)
Anodoncia/genética , Labio Leporino/genética , Fisura del Paladar/genética , Adolescente , Adulto , Anodoncia/complicaciones , Diente Premolar , Estudios de Casos y Controles , Niño , Labio Leporino/complicaciones , Fisura del Paladar/complicaciones , Diente Canino , Femenino , Sitios Genéticos , Predisposición Genética a la Enfermedad , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Netrina-1/genética , Polimorfismo de Nucleótido Simple , Adulto Joven
20.
Cleft Palate Craniofac J ; 56(7): 936-943, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30621447

RESUMEN

OBJECTIVE: To compare osseous outcomes of block and cancellous iliac bone grafting in older unilateral alveolar cleft patients. DESIGN: Retrospective and observational follow-up study. SETTING: Cleft Lip and Palate Centre, Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, China. PATIENTS: Forty-five nonsyndromic patients with unilateral complete alveolar cleft were enrolled in this study (25 patients in block bone graft group and 20 patients in cancellous bone graft group). INTERVENTIONS: In cancellous bone graft group, the alveolar cleft was filled with iliac cancellous bone particulate. In group of block bone graft, the harvested bone block was trimmed and fixed in alveolar defect. MAIN OUTCOME MEASURES: A novel method was proposed to investigate the volume and density of residual bone graft at 1-week, 3- and 6-month, 1- and 2-year postoperatively based on cone beam computed tomography scans. RESULTS: No difference in bone graft volume was found between 2 groups at 1-week and 3-month postoperatively; however, the residual volume of block bone graft group was significantly larger than that of cancellous bone graft group at 6-month, 1- and 2-year postoperatively. The bone density of block bone graft group was lower at 1-week and 3-month postoperatively but was comparable at 6-month, 1- and 2-year postoperatively. Our method was reliable and accurate to identify the range of residual bone graft when the boundary of grafted bone could not be identified clearly. CONCLUSION: Block bone graft could achieve comparable bone density and retain a greater amount of residual bone comparing to cancellous bone graft.


Asunto(s)
Injerto de Hueso Alveolar , Trasplante Óseo , Hueso Esponjoso , Labio Leporino , Fisura del Paladar , Hueso Esponjoso/trasplante , China , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Estudios de Seguimiento , Humanos , Estudios Retrospectivos , Resultado del Tratamiento
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