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AFF4 regulates osteogenic differentiation of human dental follicle cells

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 complex.AFF4 serves as a scaffolding protein that connects transcription factors and promotes gene transcription through elongation and chromatin remodelling.Here,we investigated the effect of AFF4 on human dental follicle cells(DFCs)in osteogenic differentiation.In this study,we found that small interfering RNA-mediated depletion of AFF4 resulted in decreased alkaline phosphatase(ALP)activity and impaired mineralization.In addition,the expression of osteogenic-related genes(DLX5,SP7,RUNX2 and BGLAP)was significantly downregulated.In contrast,lentivirus-mediated overexpression of AFF4 significantly enhanced the osteogenic potential of human DFCs.Mechanistically,we found that both the mRNA and protein levels of ALKBH1,a critical regulator of epigenetics,changed in accordance with AFF4 expression levels.Overexpression of ALKBH1 in AFF4-depleted DFCs partially rescued the impairment of osteogenic differentiation.Our 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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circ_0003204 regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis

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International Journal of oral Science 2022年第3期14卷 360-370页

作者： Liyuan Yu Kai Xia Jing Zhou Zhiai Hu Xing Yin Chenchen Zhou Shujuan Zou Jun Liu State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Department of Orthodontics West China Hospital of StomatologySichuan UniversityChengduChina Department of Stomatology Kunming Yan’an hospitalKunmingChina State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

Human adipose-derived stem cells(hASCs)are a promising cell type for bone tissue regeneration.Circular RNAs(circRNAs)have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis.However,how circRNAs regulate hASCs in osteogenesis is still unclear.Herein,we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs.Knockdown of circ_0003204 by si RNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs.We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p.We predicted and confirmed that miR-370-3p had targets in the 3′-UTR of HDAC4 m RNA.The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis.Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model,while overexpression of circ_0003204 inhibited bone defect repair.Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.

关键词： regulates the osteogenic differentiation of human adipose-derived stem cells via miR-370-3p/HDAC4 axis miR

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Bone morphogenetic protein 7 mediates stem cells migration and angiogenesis:therapeutic potential for endogenous pulp regeneration

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International Journal of oral Science 2022年第3期14卷 381-395页

作者： Cheng Liang Qingqing Liang Xun Xu Xiaojing Liu Xin Gao Maojiao Li Jian Yang Xiaotao Xing Haisen Huang Qi Tang Li Liao Weidong Tian State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Engineering research center of oral Translational Medicine Ministry of Education&National Engineering Laboratory for Oral Regenerative MedicineWest China Hospital of StomatologySichuan UniversityChengduChina

Pulp loss is accompanied by the functional impairment of defense,sensory,and nutrition supply.The approach based on endogenous stem cells is a potential strategy for pulp regeneration.However,endogenous stem cell sources,exogenous regenerative signals,and neovascularization are major difficulties for pulp regeneration based on endogenous stem cells.Therefore,the purpose of our research is to seek an effective cytokines delivery strategy and bioactive materials to reestablish an ideal regenerative microenvironment for pulp regeneration.In in vitro study,we investigated the effects of Wnt3a,transforming growth factor-beta 1,and bone morphogenetic protein 7(BMP7)on human dental pulp stem cells(h-DPSCs)and human umbilical vein endothelial cells.2D and 3D culture systems based on collagen gel,matrigel,and gelatin methacryloyl were fabricated to evaluate the morphology and viability of h-DPSCs.In in vivo study,an ectopic nude mouse model and an in situ beagle dog model were established to investigate the possibility of pulp regeneration by implanting collagen gel loading BMP7.We concluded that BMP7promoted the migration and odontogenic differentiation of h-DPSCs and vessel formation.Collagen gel maintained the cell adhesion,cell spreading,and cell viability of h-DPSCs in 2D or 3D culture.The transplantation of collagen gel loading BMP7 induced vascularized pulp-like tissue regeneration in vivo.The injectable approach based on collagen gel loading BMP7 might exert promising therapeutic application in endogenous pulp regeneration.

关键词： therapeutic potential for endogenous pulp regeneration Bone morphogenetic protein 7 mediates stem cells migration and angiogenesis

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Mini suture anchor: An effective device for reduction and fixation of displaced temporomandibular joint disc with intracapsular condylar fracture

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Chinese Journal of Traumatology 2022年第1期25卷 49-53页

作者： Shubhechha Shakya Kai-De Li Dou Huang Zuo-Qiang Liu Zhi-Ru Liu Lei Liu State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Department of oral and Maxillofacial Surgery West China Hospital of StomatologySichuan UniversityChengdu610041China

Purpose::The main aim is to provide clinical reference for the application of mini suture anchor in the reduction and fixation of displaced temporomandibular joint(TMJ)disc with intracapsular condylar fracture.Methods::From October 2018 to October 2019,21 patients(31 sides)with intracapsular condylar fractures and articular disc displacement from West China Hospital of Stomatology,Sichuan University were included.The selection criteria were:(1)mandibular condylar fractures accompanied by displacement of the TMJ disc,confirmed by clinical examination,CT scan and other auxiliary examinations;(2)indication for surgical treatment;(3)no surgical contraindications;(4)no previous history of surgery in the operative area;(5)no facial nerve injury before the surgery;(6)informed consent to participate in the research program and(7)complete data.Patients without surgical treatment were excluded.The employed patients were followed up at 1,3,6 and 12 months after operation.Outcomes were assessed by success rate of operation,TMJ function and radiological examination results at 3 months after operation.Data were expressed as number and percent and analyzed using SPSS 19.0.Results::All the surgical procedures were completed successfully and all the articular discs were firmly attached to the condyles.The articular disc sufficiently covered the condylar head after the fixation.The fixation remained stable when the mandible was moved in each direction by the surgeons.No complications occurred.The functions of the TMJ were well-recovered postoperatively in most cases.CT scan revealed that the screws were completely embedded in the bone without loosening or displacement.Conclusion::Mini suture anchor can provide satisfactory stabilization for the reduced articular disc and also promote the recovery of TMJ functions.

关键词： Intracapsular condylar fracture Displacement of temporomandibular joint disc Disc reduction Disc fixation Mini suture anchor

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Epigenetic regulation of mesenchymal stem cell aging through histone modifications

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Genes & diseases 2023年第6期10卷 2443-2456页

作者： Yanping Sun Haoyu Zhang Tao Qiu Li Liao Xiaoxia Su State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Department of Pediatrics&Engineering research center of oral Translational Medicine Ministry of EducationWest China Hospital of StomatologySichuan UniversityChengduSichuan 610041China

Stem cell senescence and exhaustion,a hallmark of aging,lead to declines in tissue repair and regeneration in aged individuals.Emerging evidence has revealed that epigenetic regulation plays critical roles in the self-renew,lineage-commitment,survival,and function of stem cells.Moreover,epigenetic alterations are considered important drivers of stem cell dysfunction during aging.In this review,we focused on current knowledge of the histone modifications in the aging of mesenchymal stem cells(MSCs).The aberrant epigenetic modifications on histones,including methylation and acetylation,have been found in aging MSCs.By disturbing the expression of specific genes,these epigenetic modifications affect the self-renew,survival,and differentiation of MSCs.A set of epigenetic enzymes that write or erase these modifications are critical in regulating the aging of MSCs.Furthermore,we discussed the rejuvenation strategies based on epigenetics to prevent stem cell aging and/or rejuvenate senescent MSCs.

关键词： Aging Epigenetic Histone acetylation Histone methylation Mesenchymal stem cell

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Virtual surgical planning is a useful tool in the surgical management of mandibular condylar fractures

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Chinese Journal of Traumatology 2022年第3期25卷 151-155页

作者： Shubhechha Shakya Kai-De Li Dou Huang Zuo-Qiang Liu Xiao Zhang Lei Liu state key laboratory of oral diseases&national clinical research Centre for oral diseases&Dept of Oral and Maxillofacial SurgeryWest China Hospital of StomatologySichuan UniversityChengdu610041China

Purpose:The aim of this study is to evaluate the application value of virtual surgical planning in the management of mandibular condylar fractures and to provide a reliable reference.Methods:This was a prospective randomized controlled study and recruited 50 patients requiring surgical treatment for their mandibular condylar fractures.The inclusion criteria were patients(1)diagnosed with a condylar fracture by two clinically experienced doctors and required surgical treatment;(2)have given consent for the surgical treatment;and(3)had no contraindications to the surgery.Patients were excluded from this study if:(1)they were diagnosed with a non-dislocated or only slightly dislocated condylar fracture;(2)the comminuted condylar fracture was too severe to be treated with internal reduction and fixation;or(3)patients could not complete follow-up for 3 months.There were 33 male and 17 female patients with 33 unilateral condylar fractures and 17 bilateral condylar fractures included.The 50 patients were randomly(random number)divided into control group(25 patients with 35 sides of condylar fractures)and experimental group(25 patients with 32 sides of condylar fractures).Virtual surgical planning was used in the experimental group,but only clinical experience was used in the control group.The patients were followed up for 1,3,6 and 12 months after operation.Variables including the rate of perfect reduction by radiological analysis,the average distance of deviation between preoperative and postoperative CT measurements using Geomagic software and postoperative clinical examinations(e.g.,mouth opening,occlusion)were investigated for outcome measurement.SPSS 19 was adopted for data analysis.Results:The average operation time was 180.60 min in the experimental group and 223.2 min in the control group.One week postoperatively,CT images showed that the anatomic reduction rate was 90.63%(29/32)in the experimental group and 68.57%(24/35)in the control group,revealing significant difference(X^(2)=4.919,p=0.027).Geomagic comparat

关键词： Virtual surgical planning Condylar fractures Surgical management Anatomical reduction Average distance of deviation

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Biomaterial-based strategies for maxillofacial tumour therapy and bone defect regeneration

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International Journal of oral Science 2021年第1期13卷 17-32页

作者： Bowen Tan Quan Tang Yongjin Zhong Yali Wei Linfeng He Yanting Wu Jiabao Wu Jinfeng Liao state key laboratory of oral diseases&national clinical research Centre for oral diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina

Issues caused by maxillofacial tumours involve not only dealing with tumours but also repairing jaw bone defects.In traditional tumour therapy,the systemic toxicity of chemotherapeutic drugs,invasive surgical resection,intractable tumour recurrence,and metastasis are major threats to the patients’lives in the clinic.Fortunately,biomaterial-based intervention can improve the efficiency of tumour treatment and decrease the possibility of recurrence and metastasis,suggesting new promising antitumour therapies.In addition,maxillofacial bone tissue defects caused by tumours and their treatment can negatively affect the physiological and psychological health of patients,and investment in treatment can result in a multitude of burdens to society.Biomaterials are promising options because they have good biocompatibility and bioactive properties for stimulation of bone regeneration.More interestingly,an integrated material regimen that combines tumour therapy with bone repair is a promising treatment option.Herein,we summarized traditional and biomaterial-mediated maxillofacial tumour treatments and analysed biomaterials for bone defect repair.Furthermore,we proposed a promising and superior design of dual-functional biomaterials for simultaneous tumour therapy and bone regeneration to provide a new strategy for managing maxillofacial tumours and improve the quality of life of patients in the future.

关键词： tumour maxillofacial defect

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Hard tissue stability after guided bone regeneration: a comparison between digital titanium mesh and resorbable membrane

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International Journal of oral Science 2021年第4期13卷 389-397页

作者： Songhang Li Junyi Zhao Yu Xie Taoran Tian Tianxu Zhang Xiaoxiao Cai State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases&Department of Implant dentistry West China Hospital of StomatologySichuan UniversityChengduChina

Guided bone regeneration(GBR)uses resorbable and non-resorbable membranes as biological barriers.This study compared the differences in hard tissue stability between GBR using evidence-based digital titanium mesh and resorbable collagen membranes during implant placement.A total of 40 patients(65 implant sites)were enrolled and divided into two groups:resorbable membrane and digital titanium mesh groups.The alveolar bone was analyzed at two-and three-dimensional levels using conebeam computed tomography and by reconstructing and superimposing the hard tissues at four time points:preoperatively,postoperatively,before second-stage surgery,and 1 year after loading.The use of digital titanium mesh showed less alveolar bone resorption in vertical and horizontal directions two-dimensionally before the second-stage surgery and 1 year after loading.Regarding volumetric stability,the percentage of resorption after 6 months of healing with resorbable membrane coverage reached 37.5%.However,it was only 23.4%with titanium mesh.Although postoperative bone volume was greater at all labial sites with resorbable membrane than with digital titanium mesh,after substantial bone resorption within 1 year of loading,the labial bone thickness at the upper part of implants was thinner with resorbable membrane than with digital titanium mesh.Furthermore,digital titanium meshes made according to ideal bone arch contour reduced soft tissue irritation,and the exposure rate was only 10%.Therefore,although both resorbable membrane and digital titanium mesh in GBR were able to successfully reconstruct the bone defect,digital titanium meshes were better at maintaining the hard tissue volume in the osteogenic space.

关键词： titanium stability mesh

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Aberrant NF-κB activation in odontoblasts orchestrates inflammatory matrix degradation and mineral resorption

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International Journal of oral Science 2022年第1期14卷 80-90页

作者： Fanyuan Yu Fengli Huo Feifei Li Yanqin Zuo Chenglin Wang Ling Ye State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduChina Department of Endodontics West China Stomatology HospitalSichuan UniversityChengduChina

Inflammation-associated proteinase functions are key determinants of inflammatory stromal tissues deconstruction.As a specialized inflammatory pathological process,dental internal resorption(IR)includes both soft and hard tissues deconstruction within the dentin-pulp complex,which has been one of the main reasons for inflammatory tooth loss.Mechanisms of inflammatory matrix degradation and tissue resorption in IR are largely unclear.In this study,we used a combination of Cre-loxP reporter,flow cytometry,cell transplantation,and enzyme activities assay to mechanistically investigate the role of regenerative cells,odontoblasts(ODs),in inflammatory mineral resorption and matrices degradation.We report that inflamed ODs have strong capabilities of matrix degradation and tissue resorption.Traditionally,ODs are regarded as hard-tissue regenerative cells;however,our data unexpectedly present ODs as a crucial population that participates in IR-associated tissue deconstruction.Specifically,we uncovered that nuclear factor-kappa b(NF-κB)signaling orchestrated Tumor necrosis factorα(TNF-α)-induced matrix metalloproteinases(Mmps)and Cathepsin K(Ctsk)functions in ODs to enhance matrix degradation and tissue resorption.Furthermore,TNF-αincreases Rankl/Opg ratio in ODs via NF-κB signaling by impairing Opg expression but increasing Rankl level,which utterly makes ODs cell line 17IIA11(A11)become Trap^(+) and Ctsk^(+) multinucleated cells to perform resorptive actions.Blocking of NF-κB signaling significantly rescues matrix degradation and resorptive functions of inflamed ODs via repressing vital inflammatory proteinases Mmps and Ctsk.Utterly,via utilizing NF-κB specific small molecule inhibitors we satisfactorily attenuated inflammatory ODs-associated human dental IR in vivo.Our data reveal the underlying mechanisms of inflammatory matrix degradation and resorption via proteinase activities in IR-related pathological conditions.

关键词： inflammatory matrix utilizing

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Magnesium promotes vascularization and osseointegration in diabetic states

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International Journal of oral Science 2024年第1期16卷 122-133页

作者： Linfeng Liu Feiyu Wang Wei Song Danting Zhang Weimin Lin Qi Yin Qian Wang Hanwen Li Quan Yuan Shiwen Zhang state key laboratory of oral diseases&national center for Stomatology&national clinical research center for oral diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina state key laboratory of oral diseases&national center for Stomatology&national clinical research center for oral diseases&Department of oral Implantology West China Hospital of StomatologySichuan UniversityChengduChina

Diabetes has long been considered a risk factor in implant therapy and impaired wound healing in soft and hard oral tissues.Magnesium has been proved to promote bone healing under normal conditions.Here,we elucidate the mechanism by which Mg^(2+)promotes angiogenesis and osseointegration in diabetic status.We generated a diabetic mice model and demonstrated thealveolar bone healing was compromised,with significantly decreased angiogenesis.We then developed Mg-coating implants with hydrothermal synthesis.These implants successfully improved the vascularization and osseointegration in diabetic status.Mechanically,Mg^(2+)promoted the degradation of Kelch-like ECH-associated protein 1 (Keap1) and the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) by up-regulating the expression of sestrin 2 (SESN2) in endothelial cells,thus reducing theelevated levels of oxidative stress in mitochondria and relieving endothelial cell dysfunction under hyperglycemia.Altogether,our data suggested that Mg^(2+)promoted angiogenesis and osseointegration in diabetic mice by regulating endothelial mitochondria metabolism.

关键词： healing diabetic impaired

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