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IFT140^(+)/K14^(+) cells function as stem/progenitor cells in salivary glands

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International Journal of Oral Science 2022年第4期14卷 561-571页

作者： Xueming Zhang Ji Zhou Xinyu Wang Jiangyu Geng Yubei Chen Yao Sun Department of Oral and Maxillofacial Surgery Stomatological Hospital and Dental School of Tongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationNo.399YanChang Middle RoadShanghaiChina Department of Implantology Stomatological Hospital and Dental School of Tongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationNo.399YanChang Middle RoadShanghaiChina

Stem/progenitor cells are important for salivary gland development, homeostasis maintenance, and regeneration following injury.Keratin-14^(+)(K14^(+)) cells have been recognized as bona fide salivary gland stem/progenitor cells. However, K14 is also expressed in terminally differentiated myoepithelial cells;therefore, more accurate molecular markers for identifying salivary stem/progenitor cells are required. The intraflagellar transport(IFT) protein IFT140 is a core component of the IFT system that functions in signaling transduction through the primary cilia. It is reportedly expressed in mesenchymal stem cells and plays a role in bone formation. In this study, we demonstrated that IFT140 was intensively expressed in K14^(+)stem/progenitor cells during the developmental period and early regeneration stage following ligation-induced injuries in murine submandibular glands. In addition, we demonstrated that IFT140^(+)/K14^(+)could self-renew and differentiate into granular duct cells at the developmental stage in vivo. The conditional deletion of Ift140 from K14^(+)cells caused abnormal epithelial structure and function during salivary gland development and inhibited regeneration. IFT140 partly coordinated the function of K14^(+)stem/progenitor cells by modulating ciliary membrane trafficking. Our investigation identified a combined marker, IFT140^(+)/K14^(+), for salivary gland stem/progenitor cells and elucidated the essential role of IFT140 and cilia in regulating salivary stem/progenitor cell differentiation and gland regeneration.

关键词： salivary progenitor injuries

Tracing PRX1+cells during molar formation and periodontal ligament reconstruction

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International Journal of Oral Science 2022年第1期14卷 51-59页

作者： Xuyan Gong Han Zhang Xiaoqiao Xu Yunpeng Ding Xingbo Yang Zhiyang Cheng Dike Tao Congjiao Hu Yaozu Xiang Yao Sun Department of Implantology School&Hospital of StomatologyTongji UniversityShanghaiChina Shanghai Engineering Research Center of Tooth Restoration and Regeneration ShanghaiChina shanghai East Hospital School of Life Sciences and TechnologyTongji UniversityShanghaiChina

Neural crest-derived mesenchymal stem cells(MSCs)are known to play an essential function during tooth and skeletal development.PRX1+cells constitute an important MSC subtype that is implicated in osteogenesis.However,their potential function in tooth development and regeneration remains elusive.In the present study,we first assessed the cell fate of PRX1+cells during molar development and periodontal ligament(PDL)formation in mice.Furthermore,single-cell RNA sequencing analysis was performed to study the distribution of PRX1+cells in PDL cells.The behavior of PRX1+cells during PDL reconstruction was investigated using an allogeneic transplanted tooth model.Although PRX1+cells are spatial specific and can differentiate into almost all types of mesenchymal cells in first molars,their distribution in third molars is highly limited.The PDL formation is associated with a high number of PRX1+cells;during transplanted teeth PDL reconstruction,PRX1+cells from the recipient alveolar bone participate in angiogenesis as pericytes.Overall,PRX1+cells are a key subtype of dental MSCs involved in the formation of mouse molar and PDL and participate in angiogenesis as pericytes during PDL reconstruction after tooth transplantation.

关键词： ligament molar assessed

tooth number abnormality:from bench to bedside

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International Journal of Oral Science 2023年第1期15卷 1-15页

作者： Han Zhang Xuyan Gong Xiaoqiao Xu Xiaogang Wang Yao Sun Department of Implantology Stomatological Hospital and Dental School of Tongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationShanghaiChina Key Laboratory of Big Data-Based Precision Medicine School of Engineering MedicineBeihang UniversityBeijingChina

tooth number abnormality is one of the most common dental developmental diseases,which includes both tooth agenesis and supernumerary teeth.tooth development is regulated by numerous developmental signals,such as the well-known Wnt,BMP,FGF,Shh and Eda pathways,which mediate the ongoing complex interactions between epithelium and mesenchyme.Abnormal expression of these crutial signalling during this process may eventually lead to the development of anomalies in tooth number;however,the underlying mechanisms remain elusive.In this review,we summarized the major process of tooth development,the latest progress of mechanism studies and newly reported clinical investigations of tooth number abnormality.In addition,potential treatment approaches for tooth number abnormality based on developmental biology are also discussed.This review not only provides a reference for the diagnosis and treatment of tooth number abnormality in clinical practice but also facilitates the translation of basic research to the clinical application.

关键词： abnormality diagnosis epithelium

A Transcriptomic Analysis of Physiological Significance of Hypoxia-inducible Factor-1α in Myogenesis and Carbohydrate Metabolism of Genioglossus in Mice

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Chinese Medical Journal 2017年第13期130卷 1570-1577页

作者： Tong Hao Yue-Hua Liu Yuan-Yuan Li Yun Lu Hong-Yi Xu Department of Orthodontics School and Hospital of Stomatology Tongji University Shanghai Engineering Research Center of Tooth Restoration and Regeneration Shanghai 200072 China Department of Orthodontics Shanghai Stomatological Hospital Shanghai 200001 China

Background： Chronic intermittent hypoxia is the most remarkable feature of obstructive sleep apnea/hypopnea syndrome and it can induce the change of hypoxia-inducible factor-1α （H IF-1α） expression and contractile properties in the genioglossus. To clarify the role of HIF-lot in contractile properties of the genioglossus, this study generated and compared high-throughput RNA-sequencing data from genioglossus between HIF-1α conditional knockout （KO） mice and littermate wild-type （WT） mice. Methods： KO mice were generated with cre-loxP strategy. Gene expression profile analysis was performed using gene enrichment analysis. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analyses of differently expressed messenger RNAs were performed to identify the related pathways and biological lhnctions. Six differentially expressed genes （DEGs） were validated by qualitative reverse transcription polymerase chain reaction. Results： A total of 142 （77 upregulated and 65 downregulated） transcripts were found to exhibit statistically significant difference between the HIF-la-KO and WT mice. GO and KEGG analyses indicated that DEGs included genes involved in ＂skeletal muscle cell differentiation,＂＂muscle organ development,＂＂glucose metabolic process,＂＂glycogen biosynthetic and metabolic process,＂ etc. Conclusion： This study might provide evidence that H IF-lot affects the expression of multiple genes involved in the myogenesis, muscle developrnent, and carbohydrate metabolism through transcriptome analysis in conditional HIE-1α-KO mice.

关键词： Carbohydrate Metabolism Genioglossus Hypoxia-inducible Factor-1α Myogenesis Transcriptomic Analysis

The development of collagen based composite scaffolds for bone regeneration

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Bioactive Materials 2018年第1期3卷 129-138页

作者： Dawei Zhang Xiaowei Wu Jingdi Chen Kaili Lin School&Hospital of Stomatology Tongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationShanghai 200072China Institute of Biomedical and Pharmaceutical Technology Fuzhou UniversityFuzhou 350002China

Bone is consisted of bone matrix,cells and bioactive factors,and bone matrix is the combination of inorganic minerals and organic polymers.Type I collagen fibril made of five triple-helical collagen chains is the main organic polymer in bone matrix.It plays an important role in the bone formation and remodeling process.Moreover,collagen is one of the most commonly used scaffold materials for bone tissue engineering due to its excellent biocompatibility and biodegradability.However,the low mechanical strength and osteoinductivity of collagen limit its wider applications in bone regeneration field.By incorporating different biomaterials,the properties such as porosity,structural stability,osteoinductivity,osteogenicity of collagen matrixes can be largely improved.This review summarizes and categorizes different kinds of biomaterials including bioceramic,carbon and polymer materials used as components to fabricate collagen based composite scaffolds for bone regeneration.Moreover,the possible directions of future research and development in this field are also proposed.

关键词： Collagen Bone regeneration Composite scaffolds Biomaterials Tissue engineering

3D-printed surface promoting osteogenic differentiation and angiogenetic factor expression of BMSCs on Ti6Al4V implants and early osseointegration in vivo

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Journal of Materials Science & Technology 2019年第2期35卷 336-343页

作者： Jinkai Zhang Wenhui Zhou Hui Wang Kaili Lin Fengshan Chen Department of Orthodontics School & Hospital of Stomatology Tongji University Shanghai Engineering Research Center of Tooth Restoration and Regeneration Department of Oral & Cranio-Maxillofacial Surgery Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Shanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology

Three-dimensional-printed(3 D-P) titanium implants display many advantages, such as design flexibility,higher efficiency, the capability to easily construct complex or customized structures, etc., and is believed to potentially replace traditional implants. However, the biological performance of the 3 D-P titanium surface has not been investigated systematically. Herein, we analyzed the surface characteristics of 3 D-P Ti6 Al4 V implants and evaluated the biological responses of bone marrow derived mesenchymal stromal cells(BMSCs) to the 3 D-P surface in vitro. Moreover, after implantation into the rat femoral condyle for3 and 6 weeks, the osseointegration performance was evaluated. The results showed the 3 D-P Ti6 Al4 V implant presented distinct fluctuant macroscale rough surface and relatively better hydrophilicity which enhanced the adhesion, proliferation, osteogenic differentiation and angiogenetic factor expression of BMSCs. Moreover, the in vivo osseointegration performance was also better than that of the control group at the early stage. The present study suggested the 3 D-P titanium alloy is a promising candidate to be used as implant material.

关键词： Three-dimensional printing Titanium alloy BMSCs Osteogenesis Osseointegration

Pharmacological manipulation of macrophage autophagy effectively rejuvenates the regenerative potential of biodegrading vascular graft in aging body

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Bioactive Materials 2022年第5期7卷 283-299页

作者： Wanli Chen Weiwei Xiao Xuzheng Liu Pingping Yuan Siqian Zhang Yinggang Wang Wei Wu State Key Laboratory of Military Stomatology&National Clinical research center for Oral Diseases&Shaanxi Key Laboratory of Stomatology Department of Oral&Maxillofacial SurgerySchool of StomatologyThe Fourth Military Medical UniversityXi’anShaanxiChina School&Hospital of Stomatology Tongji UniversityShanghai Engineering Research Center of Tooth Restoration and Regeneration399 Middle Yanchang RoadShanghai 200072China

Declined regenerative potential and aggravated inflammation upon aging create an inappropriate environment for arterial regeneration.Macrophages are one of vital effector cells in the immune microenvironment,especially during biomaterials mediated repairing process.Here,we revealed that the macrophage autophagy decreased with aging,which led to aggravated inflammation,thereby causing poor vascular remodeling of artificial grafts in aging body.Through loading the autophagy-targeted drugs,rapamycin and 3-MA(3-methyladenine),in PCL(polycaprolactone)sheath of the PGS(poly glycerol sebacate)-PCL vascular graft,the essential role of macrophage autophagy was confirmed in regulating macrophage polarization and biomaterial degradation.Moreover,the utilization of rapamycin promoted anti-inflammatory polarization of macrophage by activating autophagy,which further promoted myogenic differentiation of vascular progenitor cells and accelerated endothelialization.Our study elucidated the contribution of pharmacological manipulation of macrophage autophagy in promoting regeneration of small caliber artery,which may pave a new avenue for clinical translation of vascular grafts in aging body.

关键词： Autophagy Macrophages Inflammation Aging Fast-degradation materials

Autophagy mediates osteoporotic bone regeneration induced by micro-/nano-structured modification on hydroxyapatite bioceramics

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再生工程(英文)

再生工程(英文) 2023年第3期4卷 245-256页

作者： Jinjie Cui Xinran Zhang Liming Cheng Kaili Lin Department of Oral and Cranio-maxillofacial Surgery College of StomatologyNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghai Research Institute of StomatologyShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200011China Shanghai Engineering Research Center of Tooth Restoration and Regeneration School and Hospital of StomatologyTongji UniversityShanghai 200072China Department of Spine Surgery Tongji HospitalTongji University School of MedicineShanghai 200065China Ministry of Education Key Laboratory of spine and spinal cord injury repair and regeneration(Tongji University)ShanghaiChina

Osteoporosis(OP)is an age-related disease of bone metabolism,characterized by bone mass loss and bone mi-croarchitecture deterioration,the poor osteogenesis microenvironment of OP caused hardly repairing of the bone defects.As a dynamic process to fuel cellular renovation,autophagy has been proved to play a vital role in regulating cell differentiation and maintaining bone homeostasis.Traditional bone repairing biomaterials are hardly repairing the bone defects under OP pathological microenvironment.Therefore,it is essential to develop-ment novel biomaterials to improve osteoporotic osteogenesis.Compared to biochemical cues,biophysical cues exhibited more advantages in biocompatible and side effects.Herein,inspired by the importance of enhanced au-tophagic response in osteoporotic environment,we intend to utilize the micro-/nano-structured hydroxyapatite(mnHA)bioceramics as the mimic structure of natural bone tissue to regulate autophagic activity in ovariectomy bone mesenchymal stem cells(OVX-BMSCs),finally promote to bone regeneration in OP condition.The results indicated that mnHA bioceramics promoted cell adhesion and osteogenesis of OVX-BMSCs,and enhanced au-tophagy level in OVX-BMSCs.In the calvarial defects of OVX-rats,the mnHA scaffold acquired excellent bone repair effect.According to the current findings,regulating the level of autophagy could be a promising strategy for improve osteoporotic osteogenesis in the future.

关键词： Osteoporosis Osteogenesis Autophagy Hydroxyapatite Micro-/nano-structured modification

Glycosylation of dentin matrix protein 1 is critical for fracture healing via promoting chondrogenesis

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Frontiers of Medicine 2019年第5期13卷 575-589页

作者： Hui Xue Dike Tao Yuteng Weng Qiqi Fan Shuang Zhou Ruilin Zhang Han Zhang Rui Yue Xiaogang Wang Zuolin Wang Yao Sun Department of Implantology School & Hospital of StomatologyTongji UniversityShanghai Engineering Research Center of Tooth Restoration and RegenerationShanghai 200072China School & Hospital of Stomatology Tongji UniversityShanghai 200072China School of Life Sciences and Technology Tongji UniversityShanghai 200072China Beijing Advanced Innovation center for Big Data- Based Precision Medicine Beihang UniversityBeijing 100083China

Fractures are frequently occurring diseases that endanger human health. Crucial to fracture healing is cartilage formation, which provides a bone-regeneration environment. Cartilage consists of both chondrocytes and extracellular matrix (ECM). The ECM of cartilage includes collagens and various types of proteoglycans (PGs), which play important roles in maintaining primary stability in fracture healing. The PG form of dentin matrix protein 1 (DMP1-PG) is involved in maintaining the health of articular cartilage and bone. Our previous data have shown that DMP1-PG is richly expressed in the cartilaginous calluses of fracture sites. However, the possible significant role of DMP1-PG in chondrogenesis and fracture healing is unknown. To further detect the potential role of DMP1-PG in fracture repair, we established a mouse fracture model by using a glycosylation site mutant DMP1 mouse (S89G-DMP1 mouse). Upon inspection, fewer cartilaginous calluses and down-regulated expression levels of chondrogenesis genes were observed in the fracture sites of S89G-DMP1 mice. Given the deficiency of DMP1-PG, the impaired IL-6/JAK/STAT signaling pathway was observed to affect the chondrogenesis of fracture healing. Overall, these results suggest that DMP1-PG is an indispensable proteoglycan in chondrogenesis during fracture healing.

关键词： fracture extracellular matrix dentin matrix protein 1 proteoglycan cartilage