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miR-4651 inhibits cell proliferation of gingival mesenchymal stem cells by inhibiting HMGA2 under nifedipine treatment

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International Journal of Oral Science 2020年第2期12卷 132-141页

作者： Xiao Han Ruzhuang Yang Haoqing Yang Yangyang Cao Nannan Han Chen Zhang Ruitang Shi Zhengting Zhang Zhipeng Fan Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina Department of Prosthodontics Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina Department of Stomatology First Hospital of QinhuangdaoQinhuangdaoChina Department of Periodontology Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina Department of Endodontics Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina

Drug-induced gingival overgrowth(DIGO) is recognized as a side effect of nifedipine(NIF);however, the underlying molecular mechanisms remain unknown. In this study, we found that overexpressed mi R-4651 inhibits cell proliferation and induces G0/G1-phase arrest in gingival mesenchymal stem cells(GMSCs) with or without NIF treatment. Furthermore, sequential window acquisition of all theoretical mass spectra(SWATH-MS) analysis, bioinformatics analysis, and dual-luciferase report assay results confirmed that high-mobility group AT-hook 2(HMGA2) is the downstream target gene of mi R-4651. Overexpression of HMGA2 enhanced GMSC proliferation and accelerated the cell cycle with or without NIF treatment. The present study demonstrates that mi R-4651 inhibits the proliferation of GMSCs and arrests the cell cycle at the G0/G1 phase by upregulating cyclin D and CDK2 while downregulating cyclin E through inhibition of HMGA2 under NIF stimulation. These findings reveal a novel mechanism regulating DIGO progression and suggest the potential of mi R-4651 and HMGA2 as therapeutic targets.

关键词： HMGA2 gingival inhibiting

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Double heterozygous pathogenic mutations in KIF3C and ZNF513 cause hereditary gingival fibromatosis

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International Journal of Oral Science 2023年第3期15卷 489-501页

作者： Jianfan Chen Xueqing Xu Song Chen Ting Lu Yingchun Zheng Zhongzhi Gan Zongrui Shen Shunfei Ma Duocai Wang Leyi Su Fei He Xuan Shang Huiyong Xu Dong Chen Leitao Zhang Fu Xiong Department of Medical Genetics Experimental Education/Administration CenterSchool of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina Experimental Department of Obstetrics and Gynecology Institute The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Precision Medicine Shenzhen HospitalSouthern Medical UniversityShenzhenChina Department of Stomatology Nanfang HospitalSouthern Medical UniversityGuangzhouChina Department of Stomatology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Guangdong Provincial Key Laboratory of Single Cell Technology and Application GuangzhouChina Department of Fetal Medicine and Prenatal Diagnosis Zhujiang HospitalSouthern Medical UniversityGuangzhouChina

Hereditary gingival fibromatosis(HGF)is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic *** distinct loci related to non-syndromic HGF have been identified;however,only two diseasecausing genes,SOS1 and REST,inducing HGF have been identified at two loci,GINGF1 and GINGF5,***,based on a family pedigree with 26 members,including nine patients with HGF,we identified double heterozygous pathogenic mutations in the ZNF513(c.C748T,p.R250W)and KIF3C(c.G1229A,p.R410H)genes within the GINGF3 locus related to *** studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in ***513,a transcription factor,binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival ***,a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513(p.R250W)or Kif3c(p.R412H)alone do not led to clear phenotypes with gingival fibromatosis,whereas the double mutations led to gingival hyperplasia *** addition,we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of ***,the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium ***513 combined with KIF3C regulates gingival fibroblast proliferation,migration,and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK *** summary,these results demonstrate ZNF513+KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.

关键词： gingival KIF hereditary

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gingival enlargements: Differential diagnosis and review of literature

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World Journal of Clinical Cases 2015年第9期3卷 779-788页

作者： Amit Arvind Agrawal Department of Periodontics MGV’s KBH Dental college and hospital

gingival enlargement is one of the frequent features of gingival diseases. However due to their varied presentations, the diagnosis of these entities becomes challenging for the clinician. They can be categorized based on their etiopathogenesis, location, size, extent, etc. Based on the existing knowledge and clinical experience, a differential diagnosis can be formulated. Subsequently, after detailed investigation, clinician makes a final diagnosis or diagnosis of exclusion. A perfect diagnosis is critically important, since the management of these lesions and prevention of their recurrence is completely dependent on it. Furthermore, in some cases where gingival enlargement could be the primary sign of potentially lethal systemic diseases, a correct diagnosis of these enlargements could prove life saving for the patient or at least initiate early treatment and improve the quality of life. The purpose of this review article is to highlight significant findings of different types of gingival enlargement which would help clinician to differentiate between them. A detailed decision tree is also designed for the practitioners, which will help them arrive at a diagnosis in a systematic manner. There still could be some lesions which may present in an unusual manner and make the diagnosis challenging. By knowing the existence of common and rare presentations of gingival enlargement, one can keep a broad view when formulating a differential diagnosis of localized(isolated, discrete, regional) or generalized gingival enlargement.

关键词： Differential diagnosis gingival hyperplasia gingival overgrowth gingival diseases Decision tree

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gingival Fibromatosis

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1996年第1期16卷 55-57页

作者：陈卫民陈新明 Department of Stomatology Tongji Hospital Tongji Medical University Wuhan Department of Pathology College of Somatology Hubei Medical University Wuhan

Presented in this paper is a clinico-pathological report of 11 cases of gingival fibromatosis. Of the 11 patients in our series, 2 cases (18.2%) with family history began to have symptom from age of 3, which is manifested by the involvement of whole gum. 9 patients (81.8%), for which the etiology was unknown, had onset of the disease at the periods of deciduous dentition, mixed dentition or permanent dentition, with localized or overall involvement of gingiva. The disease is characterized by diffuse or localized proliferation of gum. Microscopically, the proliferating gum tissue revealed well-developed fibrotic structure with few cells; and the fibers were densely arranged without clear boundary. The fibrotic tissues showed a diminishing of blood vessels and the infiltration of inflammatory cells is not conspicuous.

关键词： gingival fibromatosis family

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Comparison of semilunar coronally repositioned flap with gingival massaging using an Ayurvedic product(irimedadi taila) in the treatment of class-Ⅰ gingival recession: A clinical study

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World Journal of Clinical Cases 2014年第10期2卷 534-540页

作者： Amit Kumar Mishra Kanteshwari Kumathalli Raja Sridhar Rahul Maru Brijesh Mangal Sameer Kedia Ravi Shrihatti ESIC Hospital Nanda Nagar Indore (M.P) 125-A Sai Bagh Colony Indore Madhya Pradesh 452001 India Sri Aurobindo College of Dentistry Village Bhawrasala Indore Madhya Pradesh 453112 India Modern Dental College and Research Centre Gandhinagar Indore Madhya Pradesh 453112 India Index Dental College Indore (M.P) 452001 India Dr. D Y Patil Dental College and Hospital Pune Maharashtra 411018 India

AIM: To study the comparison in terms of root coverage the effect of gingival massaging using an ayurvedic product and semilunar coronally repositioned flap(SCRF) to assess the treatment outcomes in the management of Miller's class Ⅰ gingival recessions over a-6mo period. METHODS: The present study comprised of total of 90 sites of Miller's class-Ⅰ gingival recessions in the maxillary anteriors, the sites were divided into three groups each comprising 30 sites, Group Ⅰ-were treated by massaging using a Placebo(Ghee) Group Ⅱ-were treated by massaging using an ayurvedic product(irimedadi taila). Group Ⅲ-were treated by SCRF. Clinical parameters assessed included recession height, recession width, probing pocket depth, width of attached gingiva, clinical attachment level and thickness of keratinized tissue. Clinical recordings were performed at baseline and 6 mo later. The results were analyzed to determine improvements in the clinical parameters. The comparison was done using Wilcoxon signed rank test. The overall differences in the clinical improvements between the three groups was done using Kruskal-Wallis test. The probability value(P-value) of less than 0.01 was considered as statistically ***: Non-surgical periodontal therapy and gingival massaging improves facial gingival recessions and prevents further progression of mucogingival defects. Root coverage was achieved in both the experimental groups. The SCRF group proved to be superior in terms of all the clinical ***: Root coverage is significantly better with semilunar coronally repositioned flap compared with the gingival massaging technique in the treatment of shallow maxillary Miller class Ⅰ gingival recession defects.

关键词： gingival recession Semilunar flaps gingival massaging Non-surgical

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gingival Metastasis Revealing Lung Adenocarcinoma

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Advances in Lung Cancer 2014年第2期3卷 35-37页

作者： Lamyae Amro Leila Maliki Badia Belabidia Abdelhaq Alaoui Yazidi Anatomopathology Departement Ibn Tofail Hospital CHU Mohammed VI FMPM Cadi Ayyad University Marrakech Morocco Pulmonary Departement Ibn Nafis Hospital CHU Mohammed VI Laboratory PCIM FMPM Cadi Ayyad University Marrakech Morocco

Introduction:?The lung adenocarcinoma is an invasive malignant tumor. Its visceral metastases are multiple. The gingival location is uncommon if not exceptional. Observation: We report the case of 66-year-old patient with a right cervical radiculopathology. Clinical examination objectified a superior vena cava syndrome with gingival tumor budding whose excisional biopsy found a location of a poorly differentiated and infiltrating carcinoma. The bronchoscopy revealed a tumor nodule obstructing the right mainstem bronchus with the histological study concluded as a moderately differentiated adenocarcinoma infiltrating. Conclusion: gingival metastasis revealing lung adenocarcinoma is uncommon even exceptional. It may delay the diagnosis and management of already poor prognosis.

关键词： gingival Metastasis Lung Cancer Adenocarcinoma

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gingival biotype: The probe test utility

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Open Journal of Stomatology 2013年第2期3卷 123-127页

作者： Madline Cuny-Houchmand Stéphane Renaudin Mustapha Leroul Lucie Planche Laurent Le Guehennec Assem Soueidan Cellule de Promotion de la Recherche Clinique CHU Nantes France Department of Orthodontics UFR d’Odontologie Nantes France Department of Periodontology UFR d’Odontologie Nantes France Department of Prosthodontics UFR d’Odontologie Nantes France

Purpose: To evaluate the relevance of the probe test in classifying the gingival biotype and to determine if differences exist between maxillary and mandibular gingival biotypes in the same patient. Materials and Methods: 53 subjects were included. The gingival thickness was evaluated as thick or thin. This evaluation was based on the transparency of the periodontal probe through the gingival margin while probing the sulcus. In another hand, 124 clinicians were asked to identify the gingival biotype in the same 53 subjects based on visual inspection on pictures. For each examiner, the accuracy in identifying the gingival biotype was assessed using the percentage of cases correctly identified. Results: the percentile of agreement is greater than 70% in maxilla as well as in mandible. An imbalance was observed on the maxillary pictures concerning the gingival biotype and on the thin biotype between maxilla and mandible despite there being no statistical difference (p gingival biotypes. Agreement between mandibular probe and maxilla probe results demonstrates a weak percentile of agreement of gingival biotypes between maxillary and mandibular anterior teeth (57%). Conclusion: The use of probe transparency through the gingival margin is an accurate and simple method for gingival biotype diagnosis to discriminate a thin gingival from a thick gingival. Furthermore, individualizing the gingival biotype for each of the arches appears to be a new outcome that needs further investigation.

关键词： Probe gingival Biotype Prevention Classification

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Pharmacological Evidence for the Involvement of Calcium Entry through TRPV1 Channels in Nifedipine-Induced [Ca<sup>2+</sup>]i Elevation in gingival Fibroblasts

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Pharmacology & Pharmacy 2012年第4期3卷 427-432页

作者： Toshimi Hattori Toshiaki Ara Yoshiaki Fujinami Department of Dental Pharmacology Matsumoto Dental University 1780 Hirooka-Gohbara Shiojiri Japan.

Background: Among anti-hypertension drugs, calcium (Ca2+) antagonists cause gingival overgrowth as a side effect. We previously discovered that this side effect was due to elevation of the calcium concentration in the cytosol ([Ca2+]i). Ca2+ entry through non-selective cation channels (NSCCs) and Ca2+ release from intracellular Ca2+ stores are involved in this [Ca2+]i elevation. Furthermore, we discovered that calcium-sensing receptors (CaSRs) participate in nifedipine-induced [Ca2+]i elevation. Transient receptor potential (TRP) channels have been identified as NSCCs. In the present study, we undertook experiments to determine if TRPV1 channels are present in gingival fibroblasts and to ascertain if nifedipine-activated NSCCs are TRPV1 channels. Methods Normal human gingival fibroblast Gin-1 cells were used. The [Ca2+]i was measured using a video-imaging analysis system with the Ca2+-sensitive fluorescent dye fura-2/AM. Results: The NSCC inhibitor SKF96365 significantly inhibited nifedipine-induced [Ca2+]i elevation. TRPV1 channel agonists such as capsaicin, olvanil and resiniferatoxin concentration-dependently elevated the [Ca2+]i. The TRPV1 channel activator anandamide concentration-dependently increased the [Ca2+]i. The TRPV1 channel antagonists capsazepine, AMG9810, iodoresiniferatoxin, ruthenium red, and SB366791 significantly inhibited nifedipine-induced [Ca2+]i elevation. Conclusion: These results suggest that Ca2+ entry through TRPV1 channels is involved in the nifedipine-induced [Ca2+]i elevation seen in gingival fibroblasts. We describe here a modified version of our ‘calcium trigger theory’.

关键词： Nifedipine gingival Overgrowth gingival Fibroblast TRPV1 Channel

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Host-derived biomarkers in gingival crevicular fluid for complementary diagnosis of apical periodontitis

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World Journal of Stomatology 2014年第2期3卷 19-24页

作者： Mauricio Garrido Andrea Dezerega Alfredo Castro-Martínez Marcela Hernández Laboratorio de Biología Periodontal Facultad de Odontología Universidad de Chile Santiago 8380492 Chile Departamento de Odontología Conservadora Facultad de Odontología Universidad de Chile Santiago 8380492 Chile Departamento de Patología y Medicina Oral Facultad de Odontología Universidad de Chile Santiago 8380492 Chile

Apical periodontitis(AP) develops as a result of the host's immune inflammatory response to pulpal infection of the dental root canals that leads to the generation of an apical lesion of endodontic origin(ALEO) and potentially to systemic metabolic alterations. Misdiagnosed ALEO is not infrequent due to the lack of diagnostic tools to differentiate apical lesions of different natures. Despite the conservative endodontic treatment shows a high success rate, there are refractory cases that can not be identified early enough during follow up. This evidences the need to develop complementary diagnostic tools, such as oral fluid biomarker analysis. gingival crevicular fluid(GCF) is a serum transudate that becomes an exudate under inflammatory conditions, carrying molecules from local periodontal tissuesand general circulation than can be harvested noninvasively. We aimed to review the available literature analyzing GCF composition in AP patients to evaluate whether GCF has any potential for complementary diagnosis. To the date, only few studies addressing changes of GCF components in AP are available. Most studies support GCF modifications in specific components in APaffected teeth, suggesting that it might reflect periapical inflammation. GCF has potential for diagnostic tool, treatment follow-up and eventually to assess systemic comprise.

关键词： gingival crevicular fluid Periapical periodontitis Biomarkers Diagnosis Prognosis

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External apical root resorption and the release of interleukin-6 in the gingival crevucular fluid induced by a self-ligating system

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Open Journal of Stomatology 2012年第2期2卷 116-121页

作者： Ryoko Kawashima-Ichinomiya Masaru Yamaguchi Yasuhiro Tanimoto Masaki Asano Kunihiko Yamada Ryo Nakajima Shoji Fujita Kazutaka Kasai Department of Dental Biomaterials Nihon University School of Dentistry at Matsudo Chiba Japan Department of Orthodontics Nihon University School of Dentistry at Matsudo Chiba Japan

The aim of this study was to investigate the amount of external apical root resorption (EARR) and the release of interleukin (IL)-6 in the gingival crevicular fluid (GCF) in subjects treated with a low-force low-friction system. Sixty patients were assigned to two groups of thirty patients for each: one group received treatment with self-ligating brackets and the other with conventional ligated edgewise brackets. All patients were treated with extraction of the maxillary first premolars. The EARR of the maxillary central incisors was evaluated on the periapical radiographs and cephalograms, taken before and after orthodontic treatment. The GCF was also collected non-invasively from the mesial and distal sides of central incisors by using filter paper strips before and after orthodontic treatment. Enzyme-linked immunosorbent assay (ELISA) kits were used to determine the IL-6 levels in the GCF samples. A significant difference was found in the amount of EARR between the patients with self-ligating brackets and conventional brackets. The mean amount of EARR was significantly lower for self-ligating brackets than conventional brackets (p < 0.05). The GCF levels of IL-6 for the patients with self-ligating brackets appliance were significantly lower than for those with the conventional brackets (p < 0.05). These results show that the mean amount of EARR and the GCF levels of IL-6 were significantly lower in the patients treated using low-force low-friction appliances than conventional brackets. Therefore, self-ligating brackets may be a useful system for reducing inflammation and EARR.

关键词： IL-6 gingival Crevucular Fluid External Apical Root Resorption Self-Ligating Brackets

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