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Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis

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International Journal of Oral Science 2024年第1期16卷 163-172页

作者： Xiao Yang Hui Zhao Rui Li Yang Chen Zhi Xu Zhengjun Shang State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyWuhan UniversityWuhanChina Department of Oral and Maxillofacial-Head and Neck Oncology School of Stomatology–Hospital of StomatologyWuhan UniversityWuhanChina Department of stomatology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model,treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs)were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (v FAOs). Consistently, treatment with arecoline reduced the expression of CD31in v FAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.

关键词： angiogenesis elevated endogenous

Expert consensus on difficulty assessment of endodontic therapy

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International Journal of Oral Science 2024年第1期16卷 15-25页

作者： Dingming Huang Xiaoyan Wang Jingping Liang Junqi Ling Zhuan Bian Qing Yu Benxiang Hou Xinmei Chen Jiyao Li Ling Ye Lei Cheng Xin Xu Tao Hu Hongkun Wu Bin Guo Qin Su Zhi Chen Lihong Qiu Wenxia Chen Xi Wei Zhengwei Huang Jinhua Yu Zhengmei Lin Qi Zhang Deqin Yang Jin Zhao Shuang Pan Jian Yang Jiayuan Wu Yihuai Pan Xiaoli Xie Shuli Deng Xiaojing Huang Lan Zhang Lin Yue Xuedong Zhou State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases&Department of Operative Dentistry and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina Department of Cariology and Endodontology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Clinical Research Center for Oral DiseasesNational Center for StomatologyShanghai Key Laboratory of StomatologyShanghaiChina Department of Operative Dentistry and Endodontics Hospital of StomatologyGuanghuaSchool of StomatologySun Yat-Sen University&Guangdong Provincial Key Laboratory of StomatologyGuangzhouChina The State Key Laboratory Breeding Base of Basic Science of stomatology(Hubei-MOST)&Key Laboratory of Oral Biomedicine Ministry of Education School and Hospital of StomatologyWuhan UniversityWuhanChina Department of Operative Dentistry&Endodontics School of StomatologyThe Fourth Military Medical UniversityXi’anChina Department of Endodontics Beijing Stomatological HospitalSchool of StomatologyCapital Medical UniversityBeijingChina State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases&Department of Preventive Dentistry West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases&Department of Geriatric dentistry West China Hospital of Stomatology

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system’s anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

关键词： anatomy difficulty treatment

Genomic alterations in oral multiple primary cancers

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International Journal of Oral Science 2024年第1期16卷 145-153页

作者： Wen Wang Qian Wang Shiying Sun Pengfei Zhang Yuyu Li Weimin Lin Qiwen Li Xiao Zhang Zhe Ma Haiyan Lu Hebei Key Laboratory of stomatology Hebei Clinical Research Center for Oral DiseasesHebei Medical UniversityShijiazhuangChina Department of Orthodontics School and Hospital of StomatologyHebei Medical UniversityShijiazhuangChina State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases&West China hospital of stomatology Sichuan UniversityChengduChina Department of Preventive Dentistry School and Hospital of StomatologyHebei Medical UniversityShijiazhuangHebeiChina

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n=202) and oral MPCs (n=34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs.Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

关键词： alterations metastasis oral

Expert consensus on irrigation and intracanal medication in root canal therapy

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International Journal of Oral Science 2024年第1期16卷 26-35页

作者： Xiaoying Zou Xin Zheng Yuhong Liang Chengfei Zhang Bing Fan Jingping Liang Junqi Ling Zhuan Bian Qing Yu Benxiang Hou Zhi Chen Xi Wei Lihong Qiu Wenxia Chen Wenxi He Xin Xu Liuyan Meng Chen Zhang Liming Chen Shuli Deng Yayan Lei Xiaoli Xie Xiaoyan Wang Jinhua Yu Jin Zhao Song Shen Xuedong Zhou Lin Yue Department of Cariology and Endodontology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Center of stomatology Peking University HospitalBeijingChina State Key Laboratory of Oral Diseases&National Center for stomatology&National Clinical Research Center for Oral Diseases&West China hospital of stomatology Sichuan UniversityChengduChina Department of Emergency Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Laboratory for Digital and Material Technology of Stomatology&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental MaterialsBeijingChina Restorative Dental Sciences EndodonticsFaculty of DentistryThe University of Hong KongPok Fu LamHong Kong SARChina State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration Key Laboratory of Oral Biomedicine Ministry of EducationHubei Key Laboratory of StomatologySchool&Hospital of StomatologyWuhan UniversityWuhanChina Department of Endodontics Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Clinical Research Center for Oral DiseasesNational Center for StomatologyShanghai Key Laboratory of StomatologyShanghaiChina Department of Operative Dentistry and Endodontics Hospital of StomatologyGuanghua School of StomatologySun Yat-Sen University&Guangdong Provincial Key Laboratory of StomatologyGuangzhouChina State Key Laboratory of Oral&Maxillofacial Reconstruction and R

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment. However, irrigant selection or irrigation procedures are far from clear. The vapor lock effect in the apical region has yet to be solved, impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.

关键词： treatment irrigation Expert

MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment

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Bone Research 2024年第1期12卷 153-164页

作者： Jiakang Yang Jing Shuai Lixuen Siow Jingyi Lu Miao Sun Wenyue An Mengfei Yu Baixiang Wang Qianming Chen stomatology hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesKey Laboratory of Oral Biomedical Research of Zhejiang ProvinceCancer Center of Zhejiang UniversityHangzhou 310000China

Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge,as chronic local inflammation can largely impair bone healing.Here,we used magnesium silicate nanospheres(MSNs)to load microRNA-146a-5p(miR-146a)to fabricate a nanobiomaterial,MSN+miR-146a,which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells(hDPSCs).In addition,miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages(BMMs)under lipopolysaccharide(LPS)stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6(TRAF6),and MSNs could simultaneously promote M2 polarization of BMMs.MiR-146a was also found to inhibit osteoclast formation.Finally,the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel.Collectively,the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oralmaxillofacial bone defects.

关键词： inflammatory healing stimulation

Clinical relevance of distolingual roots and periodontal status in mandibular first molars: a cross-sectional study employing CBCT analysis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 244-253页

作者： Feifei MAO Meng WANG Shuai ZHOU Yan ZHAO Jiaping HUANG Fengying YIN Haiping YANG Pei-hui DING stomatology hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesKey Laboratory of Oral Biomedical Research of Zhejiang ProvinceCancer Center of Zhejiang UniversityHangzhou 310016China

Objectives:Distolingual root of the permanent mandibular first molar(PMFM-DLR)has been frequently reported,which may complicate the treatment of periodontitis.This study aimed to assess the morphological features of PMFM-DLR and investigate the correlation between the morphological features of PMFM-DLR and periodontal status in patients with Eastern Chinese ethnic background.Materials and methods:A total of 836 cone beam computed tomography(CBCT)images with 1497 mandibular first molars were analyzed to observe the prevalence of PMFM-DLR at the patients and tooth levels in Eastern China.Among them,complete periodontal charts were available for 69 Chinese patients with 103 teeth.Correlation and regression analyses were used to evaluate the correlation between the morphological features of DLR,bone loss,and periodontal clinical parameters,including clinical attachment loss(CAL),probing pocket depth(PPD),gingival recession(GR),and furcation involvement(FI).Results:The patient-level prevalence and tooth-level prevalence of DLR in mandibular first molars were 29.4%and 26.3%,respectively.Multiple linear regression analysis suggested that bone loss at the lingual site and CAL were negatively affected by the angle of separation between distolingual and mesial roots in the transverse section,while they were significantly influenced by age and the angle of separation between distobuccal and mesial roots in the coronal section.Conclusions:The prevalence of PMFM-DLR in Eastern China was relatively high in our cohort.The morphological features of DLR were correlated with the periodontal status of mandibular first molars.This study provides critical information on the morphological features of DLR for improved diagnosis and treatment options of mandibular molars with DLR.

关键词： Distolingual root Mandibular first molar Periodontal clinical parameter Clinical attachment loss Cone beam computed tomography(CBCT)

Impact of scandium and terbium on the mechanical properties,corrosion behavior,and biocompatibility of biodegradable Mg-Zn-Zr-Mn alloys

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Journal of Magnesium and Alloys 2024年第2期12卷 546-572页

作者： Khurram Munir Jixing Lin Xian Tong Arne Biesiekierski Yuncang Li Cuie Wen school of Engineering RMIT UniversityMelbourneVictoria 3001Australia school and hospital of stomatology Wenzhou Medical UniversityWenzhou 325027China

Magnesium(Mg)-based bone implants degrade rapidly in the physiological environment of the human body which affects their structural integrity and biocompatibility before adequate bone repair.Rare earth elements(REEs)have demonstrated their effectiveness in tailoring the corrosion and mechanical behavior of Mg alloys.This study methodically investigated the impacts of scandium(Sc)and terbium(Tb)in tailoring the corrosion resistance,mechanical properties,and biocompatibility of Mg–0.5Zn–0.35Zr–0.15Mn(MZZM)alloys fabricated via casting and hot extrusion.Results indicate that addition of Sc and Tb improved the strength of MZZM alloys via grain size reduction and solid solution strengthening mechanisms.The extruded MZZM–(1–2)Sc–(1–2)Tb(wt.%)alloys exhibit compressive strengths within the range of 336–405 MPa,surpassing the minimum required strength of 200 MPa for bone implants by a significant margin.Potentiodynamic polarization tests revealed low corrosion rates of as–cast MZZM(0.25 mm/y),MZZM–2Tb(0.45 mm/y),MZZM–1Sc–1Tb(0.18 mm/y),and MZZM–1Sc–2Tb(0.64 mm/y),and extruded MZZM(0.17 mm/y),MZZM–1Sc(0.15 mm/y),MZZM-2Sc(0.45 mm/y),MZZM-1Tb(0.17 mm/y),MZZM-2Tb(0.10 mm/y),MZZM–1Sc-1Tb(0.14 mm/y),MZZM-1Sc-2Tb(0.40 mm/y),and MZZM–2Sc–2Tb(0.51 mm/y)alloys,which were found lower compared to corrosion rate of high-purity Mg(~1.0 mm/y)reported in the literature.Furthermore,addition of Sc,or Tb,or Sc and Tb to MZZM alloys did not adversely affect the viability of SaOS2 cells,but enhanced their initial cell attachment,proliferation,and spreading shown via polygonal shapes and filipodia.This study emphasizes the benefits of incorporating Sc and Tb elements in MZZM alloys,as they effectively enhance corrosion resistance,mechanical properties,and biocompatibility simultaneously.

关键词： Corrosion property In vitro cytotoxicity Magnesium alloys Mechanical property Rare earth elements

Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

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International Journal of Oral Science 2024年第1期16卷 110-121页

作者： Zheqi Liu Zhen Zhang Yu Zhang Wenkai Zhou Xu Zhang Canbang Peng Tong Ji Xin Zou Zhiyuan Zhang Zhenhu Ren Department of Oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyShanghaiChina Department of Oral and Maxillofacial Surgery Zhongshan HospitalFudan UniversityShanghaiChina school and hospital of stomatology Kunming Medical UniversityKunmingChina Center for Tumor Diagnosis&Therapy Jinshan HospitalFudan UniversityShanghaiChina Department of Pathology Jinshan HospitalFudan UniversityShanghaiChina Hainan Western Central hospital Academician Zhang Zhiyuan Team Innovation CenterDanzhouChina

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-βexpression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

关键词： CXCL12 microenvironment squamous

WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling

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International Journal of Oral Science 2024年第1期16卷 85-96页

作者： Qingling Huang Yi Xiao Ting Lan Youguang Lu Li Huang Dali Zheng Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFujian Medical UniversityFuzhouChina Fujian Key Laboratory of Oral Diseases School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Preventive Dentistry School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Dentistry The First Affiliated Hospital of Fujian Medical UniversityFuzhouChina

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression.These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

关键词： WNT squamous tumorigenesis