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Transforming growth factor-β in stem cells and tissue homeostasis

Bone Research 2018年第1期6卷 1-31页

作者： Xin Xu Liwei Zheng Quan Yuan Gehua Zhen Janet L.Crane Xuedong Zhou Xu Cao State Key Laboratory of oral diseases & National Clinical Research Center for oral diseases & department of Cariology and Endodontics West China Hospital of StomatologySichuan University State Key Laboratory of oral diseases & National Clinical Research Center for oral diseases & department of Pediatric Dentistry West China Hospital of Stomatology Sichuan University State Key Laboratory of oral diseases & National Clinical Research Center for oral diseases & department of oral Implantology West China Hospital of Stomatology Sichuan University department of Orthopedic Surgery Johns Hopkins University School of Medicine department of Pediatrics Johns Hopkins University

TGF-β 1–3 are unique multi-functional growth factors that are only expressed in mammals, and mainly secreted and stored as a latent complex in the extracellular matrix(ECM). The biological functions of TGF-β in adults can only be delivered after ligand activation, mostly in response to environmental perturbations. Although involved in multiple biological and pathological processes of the human body, the exact roles of TGF-β in maintaining stem cells and tissue homeostasis have not been well-documented until recent advances, which delineate their functions in a given context. Our recent findings, along with data reported by others, have clearly shown that temporal and spatial activation of TGF-β is involved in the recruitment of stem/progenitor cell participation in tissue regeneration/remodeling process, whereas sustained abnormalities in TGF-β ligand activation, regardless of genetic or environmental origin, will inevitably disrupt the normal physiology and lead to pathobiology of major diseases. Modulation of TGF-β signaling with different approaches has proven effective pre-clinically in the treatment of multiple pathologies such as sclerosis/fibrosis, tumor metastasis, osteoarthritis, and immune disorders. Thus, further elucidation of the mechanisms by which TGF-β is activated in different tissues/organs and how targeted cells respond in a context-dependent way can likely be translated with clinical benefits in the management of a broad range of diseases with the involvement of TGF-β.

关键词： cells metastasis TGF-β1 ligand human lead can not

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Transient receptor potential vanilloid 1-based gene therapy alleviates orthodontic pain in rats

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International Journal of oral Science 2019年第1期11卷 70-78页

作者： Rui Guo Yang Zhou Hu Long Di Shan Jing Wen Huimin Hu Hong Yang Zhouqiang Wu Wenli Lai State Key Laboratory of oral diseases & National Clinical Research Center for oral diseases & department of Orthodontics West China Hospital of Stomatology Sichuan University Jiangsu Key Laboratory of oral diseases Department of Orthodontics Stomatology Hospital Affiliated with Nanjing Medical University

Orthodontic pain that is induced by tooth movement is an important sequela of orthodontic treatment and has a significant effect on patient quality of life. Studies have shown that the high expression of transient receptor potential vanilloid 1(TRPV1) in trigeminal ganglions plays a vital role in the transmission and modulation of orofacial pain. However, little is known about the role of TRPV1 in orthodontic pain. In this study, male Sprague–Dawley rats were randomly assigned to six groups to study the role of TRPV1 in the modulation of tooth-movement pain. The expression levels of TRPV1 mRNA and protein were determined by real-time PCR and western blot, respectively. Moreover, pain levels were assessed using the rat grimace scale(RGS). The role of TRPV1 in modulating tooth-movement pain was examined by injecting a TRPV1 antagonist into the trigeminal ganglia of rats. A lentivirus containing a TRPV1 shRNA sequence was constructed and transduced into the rats' trigeminal ganglia. The results showed that the expression levels of TRPV1 protein and m RNA were elevated following tooth-movement pain. Pain levels increased rapidly on the1 stday, peaked on the 3^(rd) day and returned to baseline on the 14 thday. The TRPV1 antagonist significantly reduced toothmovement pain. The lentivirus containing a TRPV1 shRNA sequence was able to inhibit the expression of TRPV1 and relieved toothmovement pain. In conclusion, TRPV1-based gene therapy may be a treatment strategy for the relief of orthodontic pain.

关键词： the high expression TRPV1

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AFF4 regulates osteogenic differentiation of human dental follicle cells

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International Journal of oral Science 2020年第4期12卷 287-297页

作者： Qingyue Xiao Yuning Zhang Xingying Qi Yaqian Chen Rui Sheng Ruoshi Xu Quan Yuan Chenchen Zhou State Key Laboratory of oral diseases&National Clinical Research Center for oral diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina State Key Laboratory of oral diseases&National Clinical Research Center for oral diseases&department of Cariology and Endodontology West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of oral diseases&National Clinical Research Center for oral diseases&department of oral Implantology West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of oral diseases&National Clinical Research Center for oral diseases&department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

As a member of the AFF(AF4/FMR2)family,AFF4 is a transcription elongation factor that is a component of the super elongation ***4 serves as a scaffolding protein that connects transcription factors and promotes gene transcription through elongation and chromatin ***,we investigated the effect of AFF4 on human dental follicle cells(DFCs)in osteogenic *** this study,we found that small interfering RNA-mediated depletion of AFF4 resulted in decreased alkaline phosphatase(ALP)activity and impaired *** addition,the expression of osteogenic-related genes(DLX5,SP7,RUNX2 and BGLAP)was significantly *** contrast,lentivirus-mediated overexpression of AFF4 significantly enhanced the osteogenic potential of human ***,we found that both the mRNA and protein levels of ALKBH1,a critical regulator of epigenetics,changed in accordance with AFF4 expression *** of ALKBH1 in AFF4-depleted DFCs partially rescued the impairment of osteogenic *** data indicated that AFF4 promoted the osteogenic differentiation of DFCs by upregulating the transcription of ALKBH1.

关键词： impaired impairment alkaline

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Disturbed bone remodelling activity varies in different stages of experimental, gradually progressive apical periodontitis in rats

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International Journal of oral Science 2019年第4期11卷 289-299页

作者： Ruoshi Xu Daimo Guo Xuedong Zhou Jianxun Sun Yachuan Zhou Yi Fan Xin Zhou Mian Wan Wei Du Liwei Zheng State Key Laboratory of oral diseases National Clinical Research Center for Oral DiseasesDepartment of Cariology and EndodontologyWest China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of oral diseases National Clinical Research Center for Oral DiseasesDepartment of PediatricsWest China Hospital of StomatologySichuan UniversityChengduChina

Bone remodelling keeps going through the lifespan of human by bone formation and bone *** the craniofacial region,mandibles act as the main force for biting and chewing,and also become susceptible to a common bone-loss disease,namely,apical periodontitis,once infected dental pulp is not treated timely,during which bone resorption occurs from the apical foramen to the apical bone *** conventional root canal treatment(RCT)can remove the most of the infection,chronical apical periodontitis due to incomplete removal of dental pulp and subsequent microleakage will become refractory and more challenging,and this process has scarcely been specifically studied as a bone remodelling issue in rat ***,to study chronical and refractory apical periodontitis owing to incomplete cleaning of infected dental pulp and microleackage in vivo,we establish a modified rat model of gradually progressive apical periodontitis by sealing residual necrotic dental pulp and introducing limited saliva,which simulates gradually progressive apical periodontitis,as observed in the clinical treatment of chronical and refractory apical *** show that bone-loss is inevitable and progressive in this case of apical periodontitis,which confirms again that complete and sound root canal treatment is crucial to halt the progression of chronical and refractory apical periodontitis and promote bone ***,bone remodelling was enhanced at the initial stage of apical periodontitis in this model while reduced with a high osteoblast number afterwards,as shown by the time course study of the modified *** that the pathological apical microenvironment reserve its hard tissue formation ability to some degree but in a disturbed ***,our findings can provide insights for future bone regenerative treatment for apical periodontitisassociated bone loss.

关键词： incomplete modelling progressive

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Radiotherapy targeting cancer stem cells “awakens” them to induce tumour relapse and metastasis in oral cancer

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International Journal of oral Science 2020年第2期12卷 102-113页

作者： Yangfan Liu Miao Yang Jingjing Luo Hongmei Zhou State Key Laboratory of oral diseases&National Clinical Research Center for oral diseases&department of oral Medicine West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of oral diseases&National Clinical Research Center for oral diseases&department of Preventive Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

Radiotherapy is one of the most common treatments for oral cancer. However, in the clinic, recurrence and metastasis of oral cancer occur after radiotherapy, and the underlying mechanism remains unclear. Cancer stem cells(CSCs), considered the "seeds"of cancer, have been confirmed to be in a quiescent state in most established tumours, with their innate radioresistance helping them survive more easily when exposed to radiation than differentiated cancer cells. There is increasing evidence that CSCs play an important role in recurrence and metastasis post-radiotherapy in many cancers. However, little is known about how oral CSCs cause tumour recurrence and metastasis post-radiotherapy. In this review article, we will first summarise methods for the identification of oral CSCs and then focus on the characteristics of a CSC subpopulation induced by radiation, hereafter referred to as "awakened"CSCs, to highlight their response to radiotherapy and potential role in tumour recurrence and metastasis post-radiotherapy as well as potential therapeutics targeting CSCs. In addition, we explore potential therapeutic strategies targeting these "awakened" CSCs to solve the serious clinical challenges of recurrence and metastasis in oral cancer after radiotherapy.

关键词： metastasis tumour hereafter

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Computational technology for nasal cartilage-related clinical research and application

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International Journal of oral Science 2020年第3期12卷 183-198页

作者： Bing Shi Hanyao Huang State Key Laboratory of oral diseases&National Clinical Research Center for oral diseases&department of oral Maxillofacial Surgery West China Hospital of StomatologySichuan University610041 ChengduChina

Surgeons need to understand the effects of the nasal cartilage on facial morphology,the function of both soft tissues and hard tissues and nasal function when performing nasal *** nasal cartilage-related surgery,the main goals for clinical research should include clarification of surgical goals,rationalization of surgical methods,precision and personalization of surgical design and preparation and improved convenience of doctor–patient *** technology has become an effective way to achieve these *** in three-dimensional(3D)imaging technology will promote nasal cartilage-related applications,including research on computational modelling technology,computational simulation technology,virtual surgery planning and 3D printing *** technologies are destined to revolutionize nasal surgery *** this review,we summarize the advantages,latest findings and application progress of various computational technologies used in clinical nasal cartilage-related work and *** application prospects of each technique are also discussed.

关键词： nasal clinical application

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Cultural differences defne diagnosis and genomic medicine practice: implications for undiagnosed diseases program in China

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Frontiers of Medicine 2013年第3期7卷 389-394页

作者： Xiaohong Duan Thomas Markello David Adams Camilo Toro Cynthia Tifft William A. Gahl Cornelius F. Boerkoel department of oral Biology Clinic of Oral Rare Diseases and Genetic Diseases School of Stomatology the Fourth Military Medical University NIH Undiagnosed diseases Program NIH Offce of Rare Diseases Research and NHGRI

Despite the current acceleration and increasing leadership of Chinese genetics research,genetics and its clinical application have largely been imported to China from the *** genetics nor the scientifc reductionism underpinning its clinical application is integral to the traditional Chinese *** that disease concepts and their incumbent diagnoses are historically derived and culturally meaningful,we hypothesize that the cultural expectations of genetic diagnoses and medical genetics practice differ between the Occident and ***,we suggest that an undiagnosed diseases program in China will differ from the recently established Undiagnosed diseases Program at the United States National Institutes of Health;a culturally sensitive concept will integrate traditional Chinese understanding of disease with the scientifc reductionism of Occidental medicine.

关键词： genetics cultural differences undiagnosed diseases program

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oral health in China: from vision to action

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International Journal of oral Science 2018年第1期10卷 1-6页

作者： Xuedong Zhou Xin Xu Jiyao Li Deyu Hu Tao Hu Wei Yin Yujiang Fan Xingdong Zhang State Key Laboratory of oral diseases & National Clinical Research Center for oral diseases & department of Operative Dentistry and Endodontics West China Hospital of StomatologySichuan University State Key Laboratory of oral diseases & National Clinical Research Center for oral diseases & department of Preventive Dentistry West China Hospital of StomatologySichuan University National Engineering Research Center for Biomaterials Sichuan University

Chinese president Xi Jinping made clear at the National Health and Wellness Conference that health is the prerequisite for people’s all-around development and a precondition for the sustainable development of China. oral health is an indispensable component of overall health in humans. However, the long neglect of oral health in overall health agendas has made oral diseases an increasing concern. With this perspective, we described the global challenges of oral diseases, with an emphasis on the challenges faced by China. We also described and analyzed the recently released health policies of the Chinese government, which aim to guide midterm and long-term oral health promotion in China. More importantly, we called for specific actions to fulfill the larger goal of oral health for the nation. The implementation of primordial prevention efforts against oral diseases, the integration of oral health into the promotion of overall health, and the management of oral diseases in conjunction with other chronic non-communicable diseases with shared risk factors were highly recommended. In addition, we suggested the reform of standard clinical residency training, the development of domestic manufacturing of dental equipment and materials, the revitalization traditional Chinese medicine for the prevention and treatment of oral diseases, and integration of oral health promotion into the Belt and Road Initiative. We look forward to seeing a joint effort from all aspects of the society to fulfill the goal of Healthy China 2030 and ensure the oral health of the nation.

关键词：中国牙科口腔医学

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Expression of AT_(1a) mRNA in rat hepatic stellate cells and its effects on cell growth collagen production

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Chinese Medical Journal 2004年第5期117卷 772-774页

作者：张艺军杨希山吴平生廖贵清杨国平张晓峰陈晓清 department of Gernotology PLA Institute of Digestive diseases department of Cardiology department of oral and Maxillofacial Surgery

Activated hepatic stellate cells (HSCs) play important roles in hepatic fibrosis. Studies on HSCs activation in vitro have shown that this process is regulated by a wide variety of growth factors and cytokines.1 Recent data indicate that AngⅡ is responsible for the mechanisms of myocardial fibrosis and kidney fibrosis; but there are only few reports on hepatic fibrosis.2-8

关键词： AT 1a mRNA·angiotensinⅡ· losartan ·hepatic stellate cell

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Evaluating the potential of an amelogenin-derived peptide in tertiary dentin formation

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Regenerative Biomaterials 2021年第2期8卷 85-93页

作者： Xiu Peng Sili Han Kun Wang Longjiang Ding Zhenqi Liu Linglin Zhang State Key Laboratory of oral diseases Department of Cariology and EndodonticsNational Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengduChina

Several novel biomaterials have been developed for dental pulp capping by inducing tertiary dentin *** aim of this study was to evaluate the effect of QP5,an amelogenin-based peptide,on the mineralization of dental pulp cells(DPCs)in vitro and in *** cell viability of human DPCs(hDPCs)after treatment with QP5 was determined using the Cell Counting Kit-8(CCK-8).Migration of hDPCs was assessed using scratch assays,and the pro-mineralization effect was determined using alkaline phosphatase(ALP)staining,alizarin red staining and the expression of mineralization-related genes and *** results showed that QP5 had little effect on the cell viability,and significantly enhanced the migration capability of ***5 promoted the formation of mineralized nodules,and upregulated the activity of ALP,the expression of mRNA and proteins of mineralization-related genes.A pulp capping model in rats was generated to investigate the biological effect of *** results of micro-computed tomography and haematoxylin and eosin staining indicated that the formation of tertiary dentin in QP5-capping groups was more prominent than that in the negative control *** results indicated the potential of QP5 as a pulp therapy agent.

关键词： tertiary dentin amelogenin-derived peptide pulp capping dental pulp cells

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