{"title":"Identification and functional study of a novel variant of PAX9 causing tooth agenesis.","authors":"Rong Lei, Xili Qiu, Ying Han, Fenghua Li, Xin Dong, Saimin Pei, Ting Zeng, Minmin Ge, Zhengmao Hu, Qi Tian, Ling Peng, Junhui Huang","doi":"10.1111/odi.14937","DOIUrl":"10.1111/odi.14937","url":null,"abstract":"<p><strong>Objectives: </strong>To search for pathogenic gene of a family with non-syndromic tooth agenesis, and explore the possible pathogenesis.</p><p><strong>Materials and methods: </strong>A Chinese family with non-syndromic tooth agenesis was recruited and screened for the pathogenic variants by whole exome sequencing technology and co-segregation analysis. The subcellular localization of wild-type and mutant protein was detected by immunofluorescence assay. Cycloheximide chase assay was performed to examine the difference in degradation rate between mutant protein and wild-type one. Dual-luciferase reporter assays were conducted to explore the alterations of mutant protein in the regulation of downstream target genes.</p><p><strong>Results: </strong>A novel missense variant of PAX9 (c.296C>A:p.A99D) was found in this family. Bioinformatics software showed β-return and the random coil were shortened in the p.A99D. The variant did not affect the subcellular localization of PAX9, but the degradation rate of p.A99D was accelerated (p < 0.05). p.A99D inhibited the activation of downstream target gene BMP4 (p < 0.05).</p><p><strong>Conclusions: </strong>This novel variant expands the pathogenic gene spectrum. The variant impaired the protein structure, accelerated the degradation of protein, and inhibited the activation of the downstream target gene BMP4, an upstream molecule in the TGF-β/BMP pathway, which may contribute to tooth agenesis in this family.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":"5175-5182"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140185067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oral diseasesPub Date : 2024-11-01Epub Date: 2024-05-19DOI: 10.1111/odi.15004
Alann Thaffarell Portilho Souza, Gileade Pereira Freitas, Helena Bacha Lopes, Denise Weffort, Leticia Faustino Adolpho, Maria Paula Oliveira Gomes, Fabiola Singaretti Oliveira, Adriana Luisa Gonçalves Almeida, Marcio Mateus Beloti, Adalberto Luiz Rosa
{"title":"Efficacy of mesenchymal stem cell-based therapy on the bone repair of hypertensive rats.","authors":"Alann Thaffarell Portilho Souza, Gileade Pereira Freitas, Helena Bacha Lopes, Denise Weffort, Leticia Faustino Adolpho, Maria Paula Oliveira Gomes, Fabiola Singaretti Oliveira, Adriana Luisa Gonçalves Almeida, Marcio Mateus Beloti, Adalberto Luiz Rosa","doi":"10.1111/odi.15004","DOIUrl":"10.1111/odi.15004","url":null,"abstract":"<p><strong>Objective: </strong>Hypertension disrupts the bone integrity and its repair ability. This study explores the efficiency of a therapy based on the application of mesenchymal stem cells (MSCs) to repair bone defects of spontaneously hypertensive rats (SHR).</p><p><strong>Methods: </strong>First, we evaluated SHR in terms of bone morphometry and differentiation of MSCs into osteoblasts. Then, the effects of the interactions between MSCs from normotensive rats (NTR-MSCs) cocultured with SHR (SHR-MSCs) on the osteoblast differentiation of both cell populations were evaluated. Also, bone formation into calvarial defects of SHR treated with NTR-MSCs was analyzed.</p><p><strong>Results: </strong>Hypertension induced bone loss evidenced by reduced bone morphometric parameters of femurs of SHR compared with NTR as well as decreased osteoblast differentiation of SHR-MSCs compared with NTR-MSCs. NTR-MSCs partially restored the capacity of SHR-MSCs to differentiate into osteoblasts, while SHR-MSCs exhibited a slight negative effect on NTR-MSCs. An enhanced bone repair was observed in defects treated with NTR-MSCs compared with control, stressing this cell therapy efficacy even in bones damaged by hypertension.</p><p><strong>Conclusion: </strong>The use of MSCs derived from a heathy environment can be in the near future a smart approach to treat bone loss in the context of regenerative dentistry for oral rehabilitation of hypertensive patients.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":"5118-5128"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141064370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oral diseasesPub Date : 2024-11-01Epub Date: 2024-09-03DOI: 10.1111/odi.14870
Yuri de Lima Medeiros, Maria Emília Mota, Clóvis Antonio Lopes Pinto, Maria Stella Moreira, Fábio Abreu Alves, Graziella Chagas Jaguar
{"title":"A hard lobulated submucosal nodule on the lower lip.","authors":"Yuri de Lima Medeiros, Maria Emília Mota, Clóvis Antonio Lopes Pinto, Maria Stella Moreira, Fábio Abreu Alves, Graziella Chagas Jaguar","doi":"10.1111/odi.14870","DOIUrl":"10.1111/odi.14870","url":null,"abstract":"","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":"4811-4814"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oral diseasesPub Date : 2024-11-01Epub Date: 2024-07-05DOI: 10.1111/odi.15009
Awais Wahab, Ibrahim O Bello, Rasheed Omobolaji Alabi, Marco Mascitti, Giuseppe Troiano, Matti Mauramo, Ricardo D Coletta, Tuula Salo, Alhadi Almangush
{"title":"Web-based prognostic tools for oral tongue cancer: An analysis of online predictors.","authors":"Awais Wahab, Ibrahim O Bello, Rasheed Omobolaji Alabi, Marco Mascitti, Giuseppe Troiano, Matti Mauramo, Ricardo D Coletta, Tuula Salo, Alhadi Almangush","doi":"10.1111/odi.15009","DOIUrl":"10.1111/odi.15009","url":null,"abstract":"<p><strong>Background: </strong>Oral tongue squamous cell carcinoma (OTSCC) often presents with aggressive clinical behaviour that may require multimodality treatment based on reliable prognostication. We aimed to evaluate the prognostic ability of five online web-based tools to predict the clinical behaviour of OTSCC resection and biopsy samples.</p><p><strong>Methods: </strong>A total of 135 OTSCC resection cases and 33 OTSCC biopsies were included to predict recurrence and survival. Area under the receiver operating characteristic curves (AUC), χ<sup>2</sup> tests, and calibration plots constructed to estimate the prognostic power of each tool.</p><p><strong>Results: </strong>The tool entitled 'Prediction of risk of Locoregional Recurrences in Early OTSCC' presented an accuracy of 82%. The tool, 'Head & Neck Cancer Outcome Calculator' for 10-year cancer-related mortality had an accuracy 77% and AUC 0.858. The other tool entitled 'Cancer Survival Rates' for 5-year mortality showed an accuracy of 74% and AUC of 0.723. For biopsy samples, 'Cancer Survival Prediction Calculators' predicted the recurrence free survival with an accuracy of 70%.</p><p><strong>Conclusions: </strong>Web-based tools can aid in clinical decision making of OTSCC. Three of five online web-based tools could predict recurrence risk and cancer-related mortality in resected OTSCC and one tool could help in clinical decision making for biopsy samples.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":"4867-4877"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oral diseasesPub Date : 2024-11-01Epub Date: 2024-05-30DOI: 10.1111/odi.14973
Zheng Zhou, Xiaotian Hu, Chengpu Zhao, Jiafeng Wang, Hongfeng He
{"title":"FAM3D regulation of head and neck squamous cell carcinoma behaviour through the EMT pathway.","authors":"Zheng Zhou, Xiaotian Hu, Chengpu Zhao, Jiafeng Wang, Hongfeng He","doi":"10.1111/odi.14973","DOIUrl":"10.1111/odi.14973","url":null,"abstract":"<p><strong>Objectives: </strong>Head and neck squamous cell carcinoma present challenges in effective treatment, with 50%-60% of cases exhibiting recurrence or metastasis, often resistant to surgery alone. Immunotherapy, a promising approach, does not guarantee benefits for all patients. Thus, the imperative lies in identifying reliable biomarkers for predicting immunotherapy efficacy. FAM3D, a protein-coding gene known for its potent chemotactic activity in human peripheral blood monocytes and neutrophils, plays a crucial role in regulating tumour immune responses and holds promise as an immune biomarker.</p><p><strong>Materials and methods: </strong>We employed comprehensive database analysis to scrutinise FAM3D, evaluating its gene expression, mutation profiles and prognostic implications in head and neck squamous cell carcinoma, along with its associations with clinical characteristics and immune cell infiltration. Complementary functional experiments were conducted to delve into the potential mechanisms governed by FAM3D.</p><p><strong>Results: </strong>Our findings establish a significant correlation between low FAM3D expression and the invasiveness and metastatic potential of head and neck squamous cell carcinoma. FAM3D likely exerts its influence through the regulation of epithelial-mesenchymal transition.</p><p><strong>Conclusions: </strong>FAM3D emerges as a valuable biomarker for predicting the responsiveness of patients with head and neck squamous cell carcinoma to immunotherapy, holding substantial clinical diagnostic and therapeutic relevance.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":"4921-4938"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tooth agenesis related to a novel KDF1 variant: A case report and literature review.","authors":"Narin Intarak, Chawan Manaspon, Thanakorn Theerapanon, Sasiprapa Prommanee, Lakshman Samaranayake, Vorasuk Shotelersuk, Thantrira Porntaveetus","doi":"10.1111/odi.14930","DOIUrl":"10.1111/odi.14930","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the role of Keratinocyte Differentiation Factor 1 (KDF1) in ectodermal dysplasia (ED) and nonsyndromic tooth agenesis (NSTA) and perform a literature review.</p><p><strong>Methods: </strong>Genome sequencing was used to identify genetic variants in a Thai, NSTA proband and validated through Sanger sequencing. Pathogenicity was assessed using ACMG guidelines, MetaRNN and AlphaMissense. A comprehensive review of KDF1/NSTA cases informed genotype-phenotype analysis of the proband.</p><p><strong>Results: </strong>The proband revealed multiple missing teeth, caries and extensive periodontal disease. Deep phenotyping showed no signs of ED beyond tooth agenesis. The identified novel KDF1 variant, p.Ile243Leu, was classified as 'likely pathogenic' by ACMG and predicted as 'detrimental' by MetaRNN and AlphaMissense analyses. A total of 14 reviewed KDF1 cases revealed ED-associated variants (3 variants in 8 patients) clustering in the region of amino acids 251-275, within the DUF4656 domain, while NSTA-causing variants (4 variants in 6 patients) were typically found in amino- or carboxy-termini to this region. KDF1/NSTA cases exhibited an average of 15 missing teeth, with a higher prevalence in the mandible.</p><p><strong>Conclusion: </strong>This study identifies a novel KDF1 variant-related NSTA in Thai people. The genotype-phenotype correlates suggest a distinctive pattern and tooth agenesis of KDF1-related NSTA.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":"5195-5202"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Investigating the role of salivary Interleukin-40 levels in diagnosing periodontal diseases.","authors":"Fatma Köksel Babun, Nezahat Arzu Kayar, Mükerrem Hatipoğlu","doi":"10.1111/odi.14936","DOIUrl":"10.1111/odi.14936","url":null,"abstract":"<p><strong>Background: </strong>The present study aimed to analyze IL-40, IL-1β, and MMP-8 levels in periodontitis as well as gingivitis and periodontal health, and to explore potential correlations between these biomarkers and standard clinical parameters.</p><p><strong>Materials and methods: </strong>We collected saliva samples from 120 systemically healthy, non-smoking individuals aged between 18 and 63 years. These individuals were divided into three groups: healthy controls [S], gingivitis [G], and stage III grade B periodontitis [P]. IL-40, IL-1β, and MMP-8 levels in saliva samples were analyzed by ELISA.</p><p><strong>Results: </strong>We observed significantly elevated salivary IL-40 levels in the G group compared to the S group (p = 0.003). We found significantly higher salivary IL-1β levels in the P group compared to both the S and G groups (p = 0.000). Salivary MMP-8 levels were significantly higher in the P group than in the S group (p = 0.016).</p><p><strong>Conclusion: </strong>Our study suggests that IL-40 and IL-1β may serve as effective salivary biomarkers for diagnosing gingivitis, while MMP-8 and IL-1β may be effective for distinguishing periodontitis. Based on our study's findings, it can be stated that IL-40 may serve as a new and effective biomarker for distinguishing individuals with gingivitis from healthy ones.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":"5315-5325"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140185068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"F-actin/DRP1 axis-mediated mitochondrial fission promotes mitophagy in diabetic submandibular glands.","authors":"Hou-Wei Zhu, Yi-Ping Wang, Qiu-Fang Zhang, Kai-Di Wang, Yan Huang, Ruo-Lan Xiang","doi":"10.1111/odi.14983","DOIUrl":"10.1111/odi.14983","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is accompanied by a high prevalence of hyposalivation, causing severe damage to oral and systemic health. Mitochondrial dynamics play important roles in the pathogenesis of various diabetic complications; however, little is known about their roles in diabetic hyposalivation.</p><p><strong>Materials and methods: </strong>A diabetic mouse model and a high glucose (HG)-induced diabetic submandibular gland (SMG) cell model were employed.</p><p><strong>Results: </strong>More mitochondria surrounded by autophagosomes and higher expression of mitophagy-related proteins were detected in the SMGs of diabetic mice and HG-treated SMG cells. In diabetic SMGs, dynamin-related protein 1 (DRP1) was upregulated, whereas mitofusin-2 was downregulated both in vivo and in vitro. Shortened mitochondria and impaired mitochondrial functions were observed in the HG group. A DRP1-specific inhibitor, mdivi-1, suppressed mitochondrial fission and mitophagy, as well as restored mitochondrial functions in the HG condition. Moreover, the interaction of F-actin and DRP1 was enhanced in the diabetic group. Inhibiting F-actin with cytochalasin D repaired the injured effects of HG on mitochondrial dynamics and functions. Conversely, the F-actin-polymerization-inducer jasplakinolide aggravated mitochondrial fission and dysfunction.</p><p><strong>Conclusions: </strong>F-actin contributes to HG-evoked mitochondrial fission by interacting with DRP1, which induces mitophagy and impairs mitochondrial function in SMG cells, ultimately damaging the SMG.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":"5429-5444"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oral diseasesPub Date : 2024-11-01Epub Date: 2024-03-19DOI: 10.1111/odi.14931
Yao Wang, Yujie Sun, Bo Yang, Jun Li, Chao Liang
{"title":"The effect and mechanism of liraglutide on the biological functions of BMSCs in diabetic patients.","authors":"Yao Wang, Yujie Sun, Bo Yang, Jun Li, Chao Liang","doi":"10.1111/odi.14931","DOIUrl":"10.1111/odi.14931","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effect of liraglutide on osteogenesis in human alveolar bone marrow mesenchymal stem cells (BMSCs) and the influence of liraglutide on implant-bone integration in rats with T2DM.</p><p><strong>Subjects and methods: </strong>Extracting BMSCs from the alveoli of diabetic patients treated with insulin. BMSCs were treated with different concentrations of liraglutide. Osteogenesis and the underlying mechanism were investigated via ALP detection, ALP staining, Alizarin Red S staining, Western blotting, and RT-PCR. Liraglutide was given to Wistar and GK rats after implantation, and new bone formation around the implants was analyzed via micro-CT. Implant-bone integration in rats was investigated via toluidine blue staining.</p><p><strong>Results: </strong>Liraglutide enhanced osteogenesis in BMSCs via the BMP2/Smad/Runx2 signaling pathway. The optimal concentration of liraglutide that promoted osteogenesis was 10<sup>-8</sup> mol/L. At concentrations higher than 10<sup>-7</sup> mol/L, liraglutide had a negative effect on BMSCs. At a concentration of 10<sup>-8</sup> mol/L liraglutide, BMSCs and diabetes mellitus-bone marrow stromal cells (DM-BMSCs) showed optimal osteogenesis. Liraglutide promoted implant-bone integration and new bone formation in Wistar and GK rats.</p><p><strong>Conclusions: </strong>Liraglutide not only promotes osteogenesis of BMSCs in normoglycemic individuals but also enhances osteogenesis of BMSCs in diabetic patients treated with insulin and enhances osseointegration in rats.</p>","PeriodicalId":19615,"journal":{"name":"Oral diseases","volume":" ","pages":"5160-5174"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140158678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}