Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children...Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.展开更多
Periodontitis is the most widespread oral disease and is closely related to the oral microbiota.The oral microbiota is adversely affected by some pharmacologic treatments.Systemic antibiotics are widely used for infec...Periodontitis is the most widespread oral disease and is closely related to the oral microbiota.The oral microbiota is adversely affected by some pharmacologic treatments.Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis,causing negative effects on the human body.Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed.In this research,mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss.The results demonstrated,for the first time,that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis.Moreover,the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue.Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier,decreased the pathogenicity of the oral microbiota,reversed the Th17/Treg imbalance in periodontal tissue,and alleviated alveolar bone loss.This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis.A Th17/Treg imbalance might be related to this relationship.Importantly,these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.展开更多
Periodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate(4-OI) is...Periodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate(4-OI) is a cell-permeable itaconate derivative and has been recognized as a promising therapeutic target for the treatment of inflammatory diseases. Here, we explored, for the first time,the protective effect of 4-OI on inhibiting periodontal destruction, ameliorating local inflammation, and the underlying mechanism in periodontitis. Here we showed that 4-OI treatment ameliorates inflammation induced by lipopolysaccharide in the periodontal microenvironment. 4-OI can also significantly alleviate inflammation and alveolar bone loss via Nrf2 activation as observed on samples from experimental periodontitis in the C57BL/6 mice. This was further confirmed as silencing Nrf2 blocked the antioxidant effect of 4-OI by downregulating the expression of downstream antioxidant enzymes. Additionally, molecular docking simulation indicated the possible mechanism under Nrf2 activation. Also, in Nrf2-/-mice, 4-OI treatment did not protect against alveolar bone dysfunction due to induced periodontitis, which underlined the importance of the Nrf2 in 4-OI mediated periodontitis treatment.Our results indicated that 4-OI attenuates inflammation and oxidative stress via disassociation of KEAP1-Nrf2 and activation of Nrf2 signaling cascade. Taken together, local administration of 4-OI offers clinical potential to inhibit periodontal destruction,ameliorate local inflammation for more predictable periodontitis.展开更多
Diabetes mellitus(DM)aggravates periodontitis,resulting in accelerated periodontal bone resorption.Disordered glucose metabolism in DM causes reactive oxygen species(ROS)overproduction resulting in compromised bone he...Diabetes mellitus(DM)aggravates periodontitis,resulting in accelerated periodontal bone resorption.Disordered glucose metabolism in DM causes reactive oxygen species(ROS)overproduction resulting in compromised bone healing,which makes diabetic periodontal bone regeneration a major challenge.Inspired by the natural bone healing cascade,a mesoporous silica nanoparticle(MSN)-incorporated PDLLA(poly(DL-lactide))-PEG-PDLLA(PPP)thermosensitive hydrogel with stepwise cargo release is designed to emulate the mesenchymal stem cell“recruitment-osteogenesis”cascade for diabetic periodontal bone regeneration.During therapy,SDF-1 quickly escapes from the hydrogel due to diffusion for early rat bone marrow stem cell(rBMSC)recruitment.Simulta-neously,slow degradation of the hydrogel starts to gradually expose the MSNs for sustained release of metformin,which can scavenge the overproduced ROS under high glucose conditions to reverse the inhibited osteogenesis of rBMSCs by reactivating the AMPK/β-catenin pathway,resulting in regulation of the diabetic microenvironment and facilitation of osteogenesis.In vitro experiments indicate that the hydrogel markedly restores the inhibited migration and osteogenic capacities of rBMSCs under high glucose conditions.In vivo results suggest that it can effectively recruit rBMSCs to the periodontal defect and significantly promote periodontal bone regeneration under type 2 DM.In conclusion,our work provides a novel therapeutic strategy of a bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration.展开更多
Repairing osteoporotic bone defects is still a major clinical challenge.Recent studies have revealed that immune response is also essential in osteogenesis.The intrinsic inflammatory response of the host,especially th...Repairing osteoporotic bone defects is still a major clinical challenge.Recent studies have revealed that immune response is also essential in osteogenesis.The intrinsic inflammatory response of the host,especially the M1/M2 polarization status and inflammatory secretory function of macrophages,can directly affect osteogenic differentiation.Therefore,in this study,an electrospun naringin-loaded microspheres/sucrose acetate isobutyrate(Ng-m-SAIB)system was constructed to investigate its effect on the polarization of macrophage and osteoporotic bone defects.The results of both in vitro and in vivo experiments showed that Ng-m-SAIB had good biocompatibility and could promote the polarization of macrophage toward M2,thereby forming a favorable microenvironment for osteogenesis.The animal experiments also showed that Ng-m-SAIB could promote the osteogenesis of critical size defects in the skull of the osteoporotic model mouse(the senescence-accelerated mouse-strain P6).Together,these results collectively suggested that Ng-m-SAIB might be a promising biomaterial to treat osteoporotic bone defects with favorable osteo-immunomodulatory effects.展开更多
Extracellular vesicles(EVs)derived from mesenchymal stem cells(MSCs)have emerged as a new mode of intercellular crosstalk and are responsible for many of the thera-peutic effects of MSCs.To promote the application of ...Extracellular vesicles(EVs)derived from mesenchymal stem cells(MSCs)have emerged as a new mode of intercellular crosstalk and are responsible for many of the thera-peutic effects of MSCs.To promote the application of MSC-EVs,recent studies have focused on the manipulation of MSCs to improve the production of EVs and EV-mediated activities.The current paper details an optimization method using non-invasive low-intensity pulsed ul-trasound(LIPUS)as the stimulation for improving oral MSC-EV production and effectiveness.Stem cells from apical papilla(SCAP),a type of oral mesenchymal stem cell,displayed inten-sity-dependent pro-osteogenic and anti-inflammatory responses to LIPUS without significant cytotoxicity or apoptosis.The stimuli increased the secretion of EVs by promoting the expres-sion of neutral sphingomyelinases in SCAP.In addition,EVs from LIPUS-induced SCAP exhibited stronger efficacy in promoting the osteogenic differentiation and anti-inflammation of peri-odontal ligament cells in vitro and alleviating oral inflammatory bone loss in vivo.In addition,LIPUS stimulation affected the physical characteristics and miRNA cargo of SCAP-EVs.Further investigations indicated that miR-935 is an important mediator of the pro-osteogenic and anti-inflammatory capabilities of LIPUS-induced SCAP-EVs.Taken together,these findings demonstrate that LIPUS is a simple and effective physical method to optimize SCAP-EV produc-tion and efficacy.展开更多
Periodontitis is an oral chronic inflammatory disease.Inhibiting tissue destruction and promoting tissue regeneration are important means for the treatment of periodontitis.Metformin not only has hypoglycemic effect b...Periodontitis is an oral chronic inflammatory disease.Inhibiting tissue destruction and promoting tissue regeneration are important means for the treatment of periodontitis.Metformin not only has hypoglycemic effect but also has anti-inflammatory effect.Metformin has been shown to inhibit oxidative stress and activate autophagy through AMPK/mTOR pathway.High mobility group box 1(HMGB1)has been implicated in the pathogenesis of many inflammatory diseases including periodontitis,it can participate in the induction of oxidative stress.HMGB1 is an autophagy regulator under oxidative stress,which can activate mTOR pathway.However,it is not clear whether metformin is related to HMGB1 and its mechanism in the process of periodontitis.Cell viability and expression of inflammatory cytokines were clarified by Cell Counting Kit-8,real-time PCR and enzyme-linked immunosorbent assay.Western blot and immunofluorescence were conducted to determine HMGB1 intracellular localization and expression of autophagy-associated proteins in vitro.Experimental periodontitis mice model was induced by administering a ligature.Immunohistochemistry was performed to detect the expression and localization of HMGB1 in vivo.The results of CCK-8,real-time PCR,enzyme-linked immunosorbent assay,Western blot and immunofluorescence showed lipopolysaccharide(LPS)treatment inhibited cell viability,and increased HMGB1 expression at a dose-independent manner.Metformin can reduce the effect of LPS.It also improves autophagy pathway inhibited by LPS and down-regulates mTOR expression.In addition,metformin attenuated alveolar bone resorption induced by ligation.This study provides new evidence for that metformin is a potential drug for the treatment of periodontitis and HMGB1 may be a potential target for periodontal intervention.展开更多
This study aimed to explore the optimal invisible orthodontic force system during the en-mass distalization of two maxillary molars to minimize the side effect of anchorage loss by changing the direction of the applic...This study aimed to explore the optimal invisible orthodontic force system during the en-mass distalization of two maxillary molars to minimize the side effect of anchorage loss by changing the direction of the application of the orthodontic force system.A high bio-fidelity 3D finite element model including maxilla,periodontal ligament,dentition,clear aligner,3D anchorage attachment and mini-implant was established.Different lengths of lateral hooks of 3D-printed anchorage attachments and mini-implant positions into the palatal alveolus were considered.A 200 g distal force was applied to the lateral hooks of different horizontal lengths(3.26 mm,6.52 mm and 9.78 mm)with the mini-implant as the application point.Using ABAQUS software,orthodontic tooth movements under 12 different clinical treatment designs were analyzed and calculated.The 3D anchorage attachment enhanced the anchorage of anterior teeth and alleviated the tipping/extrusion of premolars.In contrast to without clear aligners,length of the lateral hook had a negligible effect on both mesial tipping and buccal tipping with clear aligners,which could then be ignored.The change in mesial tipping was less and nearly remained constant despite of the different heights of the mini-implant.The 3D anchorage attachment assisted clear aligner can avoid the side effects of anterior tooth proclination caused by insufficient anchorage.The length of the lateral hook,and height of the mini-implant in this invisible orthodontic force system hardly affects the tooth movement of anchorage units.Clear aligners can effectively control the rotation and tipping of anchorage units caused by 3D anchorage attachment.展开更多
Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling.Serious injuries and/or loss of tooth or periodontal tissues ma...Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling.Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance,essential oral functions and the quality of life.Regenerative dentistry holds great promise in treating oral/dental disorders.The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells,along with the signaling mechanisms governing stem cell self-renewal and differentiation.In this review,we first summarize the biological characteristics of seven types of dental stem cells,including dental pulp stem cells,stem cells from apical papilla,stem cells from human exfoliated deciduous teeth,dental follicle precursor cells,periodontal ligament stem cells,alveolar bone-derived mesenchymal stem cells(MSCs),and MSCs from gingiva.We then focus on how these stem cells are regulated by bone morphogenetic protein(BMP)and/or Wnt signaling by examining the interplays between these pathways.Lastly,we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways.We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications.Thus,we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade.展开更多
Precise and controlled drug delivery to treat periodontitis in patients with diabetes remains a significant clinical challenge.Nanoparticle-based drug delivery systems offer a potential therapeutic strategy;however,th...Precise and controlled drug delivery to treat periodontitis in patients with diabetes remains a significant clinical challenge.Nanoparticle-based drug delivery systems offer a potential therapeutic strategy;however,the low loading efficiency,non-responsiveness,and single effect of conventional nanoparticles hinder their clinical application.In this study,we designed a novel self-assembled,dual responsive,and dual drug-loading nanocarrier system,which comprised two parts:the hydrophobic lipid core formed by 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol)(DSPE-PEG)loaded with alpha-lipoic acid(ALA);and a hydrophilic shell comprising a poly(amidoamine)dendrimer(PAMAM)that electrostatically adsorbed minocycline hydrochloride(Mino).This unique design allows the controlled release of antioxidant/ALA under lipase stimulation from periodontal pathogens and antimicrobial/Mino under the low pH of the inflammatory microenvironment.In vivo and in vitro studies confirmed that this dual nanocarrier could inhibit the formation of subgingival microbial colonies while promoting osteogenic differentiation of cells under diabetic pathological conditions,and ameliorated periodontal bone resorption.This effective and versatile drug-delivery strategy has good potential applications to inhibit diabetes-associated periodontal bone loss.展开更多
Local drug delivery has received increasing attention in recent years.However,the therapeutic efficacy of local delivery of drugs is still limited under certain scenarios,such as in the oral cavity or in wound beds af...Local drug delivery has received increasing attention in recent years.However,the therapeutic efficacy of local delivery of drugs is still limited under certain scenarios,such as in the oral cavity or in wound beds after resection of tumors.In this study,we introduce a bioinspired adhesive hydrogel derived from the skin secretions of Andrias davidianus(SSAD)as a wound dressing for localized drug elution.The hydrogel was loaded with aminoguanidine or doxorubicin,and its controlled drug release and healing-promoting properties were verified in a diabetic rat palatal mucosal defect model and a C57BL/6 mouse melanoma-bearing model,respectively.The results showed that SSAD hydrogels with different pore sizes could release drugs in a controllable manner and accelerate wound healing.Transcriptome analyses of the palatal mucosa suggested that SSAD could significantly upregulate pathways linked to cell adhesion and extracellular matrix deposition and had the ability to recruit keratinocyte stem cells to defect sites.Taken together,these findings indicate that property-controllable SSAD hydrogels could be a promising biofunctional wound dressing for local drug delivery and promotion of wound healing.展开更多
基金supported by the National Natural Science Foundation of China(82171001,82222015)Research Funding from West China School/Hospital of Stomatology Sichuan University(RCDWJS2023-1)Align Technology Specialized Scientific Research Fund(21H0922).
文摘Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.
基金supported by grants 31971282,U22A20314(to J.S.),82170968(to T.Z.)from the National Natural Science Foundation of Chinasupported by dstd201903(to J.S.)from the 2019 Chongqing Graduate Tutor Team Construction Project2022YFC2504200(to J.S.)from National Key R&D of Program of China。
文摘Periodontitis is the most widespread oral disease and is closely related to the oral microbiota.The oral microbiota is adversely affected by some pharmacologic treatments.Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis,causing negative effects on the human body.Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed.In this research,mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss.The results demonstrated,for the first time,that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis.Moreover,the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue.Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier,decreased the pathogenicity of the oral microbiota,reversed the Th17/Treg imbalance in periodontal tissue,and alleviated alveolar bone loss.This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis.A Th17/Treg imbalance might be related to this relationship.Importantly,these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.
基金supported by the National Natural Science Foundation of China (31971282 and 32071362)2019 Chongqing Graduate Tutor Team Construction Project (dstd201903)Scientific and Technological Research Program of Chongqing Municipal Education Commission (KJQN201900415)。
文摘Periodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate(4-OI) is a cell-permeable itaconate derivative and has been recognized as a promising therapeutic target for the treatment of inflammatory diseases. Here, we explored, for the first time,the protective effect of 4-OI on inhibiting periodontal destruction, ameliorating local inflammation, and the underlying mechanism in periodontitis. Here we showed that 4-OI treatment ameliorates inflammation induced by lipopolysaccharide in the periodontal microenvironment. 4-OI can also significantly alleviate inflammation and alveolar bone loss via Nrf2 activation as observed on samples from experimental periodontitis in the C57BL/6 mice. This was further confirmed as silencing Nrf2 blocked the antioxidant effect of 4-OI by downregulating the expression of downstream antioxidant enzymes. Additionally, molecular docking simulation indicated the possible mechanism under Nrf2 activation. Also, in Nrf2-/-mice, 4-OI treatment did not protect against alveolar bone dysfunction due to induced periodontitis, which underlined the importance of the Nrf2 in 4-OI mediated periodontitis treatment.Our results indicated that 4-OI attenuates inflammation and oxidative stress via disassociation of KEAP1-Nrf2 and activation of Nrf2 signaling cascade. Taken together, local administration of 4-OI offers clinical potential to inhibit periodontal destruction,ameliorate local inflammation for more predictable periodontitis.
基金National Natural Science Foundation of China(Grant No.31971282 and 82071072)Chongqing Graduate Tutor Team 2019(dstd201903).
文摘Diabetes mellitus(DM)aggravates periodontitis,resulting in accelerated periodontal bone resorption.Disordered glucose metabolism in DM causes reactive oxygen species(ROS)overproduction resulting in compromised bone healing,which makes diabetic periodontal bone regeneration a major challenge.Inspired by the natural bone healing cascade,a mesoporous silica nanoparticle(MSN)-incorporated PDLLA(poly(DL-lactide))-PEG-PDLLA(PPP)thermosensitive hydrogel with stepwise cargo release is designed to emulate the mesenchymal stem cell“recruitment-osteogenesis”cascade for diabetic periodontal bone regeneration.During therapy,SDF-1 quickly escapes from the hydrogel due to diffusion for early rat bone marrow stem cell(rBMSC)recruitment.Simulta-neously,slow degradation of the hydrogel starts to gradually expose the MSNs for sustained release of metformin,which can scavenge the overproduced ROS under high glucose conditions to reverse the inhibited osteogenesis of rBMSCs by reactivating the AMPK/β-catenin pathway,resulting in regulation of the diabetic microenvironment and facilitation of osteogenesis.In vitro experiments indicate that the hydrogel markedly restores the inhibited migration and osteogenic capacities of rBMSCs under high glucose conditions.In vivo results suggest that it can effectively recruit rBMSCs to the periodontal defect and significantly promote periodontal bone regeneration under type 2 DM.In conclusion,our work provides a novel therapeutic strategy of a bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration.
基金support from the National Natural Science Foundation of China(No.81970914).
文摘Repairing osteoporotic bone defects is still a major clinical challenge.Recent studies have revealed that immune response is also essential in osteogenesis.The intrinsic inflammatory response of the host,especially the M1/M2 polarization status and inflammatory secretory function of macrophages,can directly affect osteogenic differentiation.Therefore,in this study,an electrospun naringin-loaded microspheres/sucrose acetate isobutyrate(Ng-m-SAIB)system was constructed to investigate its effect on the polarization of macrophage and osteoporotic bone defects.The results of both in vitro and in vivo experiments showed that Ng-m-SAIB had good biocompatibility and could promote the polarization of macrophage toward M2,thereby forming a favorable microenvironment for osteogenesis.The animal experiments also showed that Ng-m-SAIB could promote the osteogenesis of critical size defects in the skull of the osteoporotic model mouse(the senescence-accelerated mouse-strain P6).Together,these results collectively suggested that Ng-m-SAIB might be a promising biomaterial to treat osteoporotic bone defects with favorable osteo-immunomodulatory effects.
基金supported by the National Natural Science Foundation of China(No.81771082,81800985,82170968,31971282)the 2019 Chongqing Graduate Tutor Team Construction Project(No.dstd201903),Chinathe Natural Science Foundation of Chongqing(No.cstc2019jcyj-msxmX0851),China.
文摘Extracellular vesicles(EVs)derived from mesenchymal stem cells(MSCs)have emerged as a new mode of intercellular crosstalk and are responsible for many of the thera-peutic effects of MSCs.To promote the application of MSC-EVs,recent studies have focused on the manipulation of MSCs to improve the production of EVs and EV-mediated activities.The current paper details an optimization method using non-invasive low-intensity pulsed ul-trasound(LIPUS)as the stimulation for improving oral MSC-EV production and effectiveness.Stem cells from apical papilla(SCAP),a type of oral mesenchymal stem cell,displayed inten-sity-dependent pro-osteogenic and anti-inflammatory responses to LIPUS without significant cytotoxicity or apoptosis.The stimuli increased the secretion of EVs by promoting the expres-sion of neutral sphingomyelinases in SCAP.In addition,EVs from LIPUS-induced SCAP exhibited stronger efficacy in promoting the osteogenic differentiation and anti-inflammation of peri-odontal ligament cells in vitro and alleviating oral inflammatory bone loss in vivo.In addition,LIPUS stimulation affected the physical characteristics and miRNA cargo of SCAP-EVs.Further investigations indicated that miR-935 is an important mediator of the pro-osteogenic and anti-inflammatory capabilities of LIPUS-induced SCAP-EVs.Taken together,these findings demonstrate that LIPUS is a simple and effective physical method to optimize SCAP-EV produc-tion and efficacy.
基金supported by the National Natural Science Foundation of China(No.81771082,31971282)Scientific and Technological Research Program of Chongqing Municipal Education Commission,China(No.KJQN202000417)Chongqing Graduate Tutor Team,China(2019).
文摘Periodontitis is an oral chronic inflammatory disease.Inhibiting tissue destruction and promoting tissue regeneration are important means for the treatment of periodontitis.Metformin not only has hypoglycemic effect but also has anti-inflammatory effect.Metformin has been shown to inhibit oxidative stress and activate autophagy through AMPK/mTOR pathway.High mobility group box 1(HMGB1)has been implicated in the pathogenesis of many inflammatory diseases including periodontitis,it can participate in the induction of oxidative stress.HMGB1 is an autophagy regulator under oxidative stress,which can activate mTOR pathway.However,it is not clear whether metformin is related to HMGB1 and its mechanism in the process of periodontitis.Cell viability and expression of inflammatory cytokines were clarified by Cell Counting Kit-8,real-time PCR and enzyme-linked immunosorbent assay.Western blot and immunofluorescence were conducted to determine HMGB1 intracellular localization and expression of autophagy-associated proteins in vitro.Experimental periodontitis mice model was induced by administering a ligature.Immunohistochemistry was performed to detect the expression and localization of HMGB1 in vivo.The results of CCK-8,real-time PCR,enzyme-linked immunosorbent assay,Western blot and immunofluorescence showed lipopolysaccharide(LPS)treatment inhibited cell viability,and increased HMGB1 expression at a dose-independent manner.Metformin can reduce the effect of LPS.It also improves autophagy pathway inhibited by LPS and down-regulates mTOR expression.In addition,metformin attenuated alveolar bone resorption induced by ligation.This study provides new evidence for that metformin is a potential drug for the treatment of periodontitis and HMGB1 may be a potential target for periodontal intervention.
基金This work was supported by the National Natural Science Foundation of China(Grant No.12072055,11872135,U20A20390,U22A20314)Natural Science Foundation of Beijing(Grant No.L212063)+3 种基金the Fundamental Research Funds for the Central Universities,the 111 Project(No.B13003)the National Research Program of China(Grant No.2022YFC2504200)Orthodontic research project of youth clinical research fund of Chinese Stomatological Association(Grant No.CSA-O2020-07)Municipal graduate tutor team construction project(dstd201903).
文摘This study aimed to explore the optimal invisible orthodontic force system during the en-mass distalization of two maxillary molars to minimize the side effect of anchorage loss by changing the direction of the application of the orthodontic force system.A high bio-fidelity 3D finite element model including maxilla,periodontal ligament,dentition,clear aligner,3D anchorage attachment and mini-implant was established.Different lengths of lateral hooks of 3D-printed anchorage attachments and mini-implant positions into the palatal alveolus were considered.A 200 g distal force was applied to the lateral hooks of different horizontal lengths(3.26 mm,6.52 mm and 9.78 mm)with the mini-implant as the application point.Using ABAQUS software,orthodontic tooth movements under 12 different clinical treatment designs were analyzed and calculated.The 3D anchorage attachment enhanced the anchorage of anterior teeth and alleviated the tipping/extrusion of premolars.In contrast to without clear aligners,length of the lateral hook had a negligible effect on both mesial tipping and buccal tipping with clear aligners,which could then be ignored.The change in mesial tipping was less and nearly remained constant despite of the different heights of the mini-implant.The 3D anchorage attachment assisted clear aligner can avoid the side effects of anterior tooth proclination caused by insufficient anchorage.The length of the lateral hook,and height of the mini-implant in this invisible orthodontic force system hardly affects the tooth movement of anchorage units.Clear aligners can effectively control the rotation and tipping of anchorage units caused by 3D anchorage attachment.
基金The authors apologize to those investigators whose original work was not cited due to space constraints.The authors’research was supported in part by research grants from the National Institutes of Health(AT004418&AR054381 to TCH&HHL)Scoliosis Research Society(MJL&TCH),the 973 Program of Ministry of Science and Technology(MOST)of China(#2011CB707900 to TCH),the National Natural Science Foundation of China(#81400493 to FZ)+2 种基金Chongqing Municipal Commissions on Education(#KJ130303 to JW)Chongqing Municipal Commissions on Science&Technology(#cstc2013jcyjA0093 to JW)Chongqing Municipal Commissions Yubei District Science&Technology(#2014 Society of Human Resource Unit 14 to JW).MKM was a recipient of Howard Hughes Medical Institute Medical Research Fellowship.
文摘Tooth is a complex hard tissue organ and consists of multiple cell types that are regulated by important signaling pathways such as Wnt and BMP signaling.Serious injuries and/or loss of tooth or periodontal tissues may significantly impact aesthetic appearance,essential oral functions and the quality of life.Regenerative dentistry holds great promise in treating oral/dental disorders.The past decade has witnessed a rapid expansion of our understanding of the biological features of dental stem cells,along with the signaling mechanisms governing stem cell self-renewal and differentiation.In this review,we first summarize the biological characteristics of seven types of dental stem cells,including dental pulp stem cells,stem cells from apical papilla,stem cells from human exfoliated deciduous teeth,dental follicle precursor cells,periodontal ligament stem cells,alveolar bone-derived mesenchymal stem cells(MSCs),and MSCs from gingiva.We then focus on how these stem cells are regulated by bone morphogenetic protein(BMP)and/or Wnt signaling by examining the interplays between these pathways.Lastly,we analyze the current status of dental tissue engineering strategies that utilize oral/dental stem cells by harnessing the interplays between BMP and Wnt pathways.We also highlight the challenges that must be addressed before the dental stem cells may reach any clinical applications.Thus,we can expect to witness significant progresses to be made in regenerative dentistry in the coming decade.
基金the National Natural Science Foundation of China(Grant Nos.82171010,81771082,31971282,82001103)the Basic Research and Frontier Exploration Grant of Chongqing Science and Technology Commission(Grant Nos.cstc2021jcyj-jqX0028,cstc2019jcyj-msxmX0366,cstc2019jcyj-bshX0005)+2 种基金the“Associate Doctoral Supervisor”Cultivation Fund of the Stomatological Hospital of Chongqing Medical University(Grant No.KQFBD002)the Project of the Scientific and Technological Research Program of Chongqing Municipal Education Commission(Grant No.KJQN201900441)and the Chongqing Graduate Tutor Team(Grant No.dstd201903).
文摘Precise and controlled drug delivery to treat periodontitis in patients with diabetes remains a significant clinical challenge.Nanoparticle-based drug delivery systems offer a potential therapeutic strategy;however,the low loading efficiency,non-responsiveness,and single effect of conventional nanoparticles hinder their clinical application.In this study,we designed a novel self-assembled,dual responsive,and dual drug-loading nanocarrier system,which comprised two parts:the hydrophobic lipid core formed by 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol)(DSPE-PEG)loaded with alpha-lipoic acid(ALA);and a hydrophilic shell comprising a poly(amidoamine)dendrimer(PAMAM)that electrostatically adsorbed minocycline hydrochloride(Mino).This unique design allows the controlled release of antioxidant/ALA under lipase stimulation from periodontal pathogens and antimicrobial/Mino under the low pH of the inflammatory microenvironment.In vivo and in vitro studies confirmed that this dual nanocarrier could inhibit the formation of subgingival microbial colonies while promoting osteogenic differentiation of cells under diabetic pathological conditions,and ameliorated periodontal bone resorption.This effective and versatile drug-delivery strategy has good potential applications to inhibit diabetes-associated periodontal bone loss.
基金supported by the National Natural Science Foundation of China(32070826,81801929)the Chinese Postdoctoral Science Foundation(2019M650239,2020T130762)+4 种基金the Chongqing Research Program of Basic Research and Frontier Technology(cstc2018jcyjAX0807)the Innovative Talents Project of Chongqing Postdoctoral Foundation(YRSB(2019)298)the Chongqing Medical Joint Research Project of Chongqing Science and Technology Committee&Health Agency(2020GDRC017)Chongqing Graduate Tutor Team Project(dstd201903)the Medical Research Project of Chongqing Health and Family Planning Commission(2017ZDXM016)。
文摘Local drug delivery has received increasing attention in recent years.However,the therapeutic efficacy of local delivery of drugs is still limited under certain scenarios,such as in the oral cavity or in wound beds after resection of tumors.In this study,we introduce a bioinspired adhesive hydrogel derived from the skin secretions of Andrias davidianus(SSAD)as a wound dressing for localized drug elution.The hydrogel was loaded with aminoguanidine or doxorubicin,and its controlled drug release and healing-promoting properties were verified in a diabetic rat palatal mucosal defect model and a C57BL/6 mouse melanoma-bearing model,respectively.The results showed that SSAD hydrogels with different pore sizes could release drugs in a controllable manner and accelerate wound healing.Transcriptome analyses of the palatal mucosa suggested that SSAD could significantly upregulate pathways linked to cell adhesion and extracellular matrix deposition and had the ability to recruit keratinocyte stem cells to defect sites.Taken together,these findings indicate that property-controllable SSAD hydrogels could be a promising biofunctional wound dressing for local drug delivery and promotion of wound healing.
