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Metabolic memory:mechanisms and diseases

Signal Transduction and Targeted Therapy 2024年第3期9卷 1086-1114页

作者： Hao Dong Yuezhang Sun Lulingxiao Nie Aimin Cui Pengfei Zhao Wai Keung Leung Qi Wang State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduChina Department of Prosthodontics West China Hospital of StomatologySichuan UniversityChengduChina periodontology and implant dentistry division Faculty of DentistryThe University of Hong KongHong KongChina

Metabolic diseases and their complications impose health and economic burdens *** from past experimental studies and clinical trials suggests our body may have the ability to remember the past metabolic environment,such as hyperglycemia or hyperlipidemia,thus leading to chronic inflammatory disorders and other diseases even after the elimination of these metabolic *** long-term effects of that aberrant metabolism on the body have been summarized as metabolic memory and are found to assume a crucial role in states of health and *** molecular mechanisms collectively participate in metabolic memory management,resulting in different cellular alterations as well as tissue and organ dysfunctions,culminating in disease progression and even affecting *** elucidation and expansion of the concept of metabolic memory provides more comprehensive insight into pathogenic mechanisms underlying metabolic diseases and complications and promises to be a new target in disease detection and ***,we retrace the history of relevant research on metabolic memory and summarize its salient *** provide a detailed discussion of the mechanisms by which metabolic memory may be involved in disease development at molecular,cellular,and organ levels,with emphasis on the impact of epigenetic ***,we present some of the pivotal findings arguing in favor of targeting metabolic memory to develop therapeutic strategies for metabolic diseases and provide the latest reflections on the consequences of metabolic memory as well as their implications for human health and diseases.

关键词： diseases metabolism alterations

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Immunomodulatory properties of dental tissue-derived mesenchymal stem cells: Implication in disease and tissue regeneration

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World Journal of Stem Cells 2019年第9期11卷 604-617页

作者： Oleh Andrukhov Christian Behm Alice Blufstein Xiaohui Rausch-Fan division of Conservative dentistry and periodontology University Clinic of Dentistry Medical University of Vienna

Mesenchymal stem cells(MSCs)are considered as an attractive tool for tissue regeneration and possess a strong immunomodulatory *** tissuederived MSCs can be isolated from different sources,such as the dental pulp,periodontal ligament,deciduous teeth,apical papilla,dental follicles and *** to numerous in vitro studies,the effect of dental MSCs on immune cells might depend on several factors,such as the experimental setting,MSC tissue source and type of immune cell *** studies have shown that the immunomodulatory activity of dental MSCs is strongly upregulated by activated immune *** exert mostly immunosuppressive effects,leading to the dampening of immune cell ***,the reciprocal interaction between dental MSCs and immune cells represents an elegant mechanism that potentially contributes to tissue homeostasis and inflammatory disease *** the immunomodulatory potential of dental MSCs has been extensively investigated in vitro,its role in vivo remains obscure.A few studies have reported that the MSCs isolated from inflamed dental tissues have a compromised immunomodulatory ***,the expression of some immunomodulatory proteins is enhanced in periodontal disease and even shows some correlation with disease ***-based immunomodulation may play an essential role in the regeneration of different dental ***,immunomodulation-based strategies may be a very promising tool in regenerative dentistry.

关键词： Mesenchymal stem cells Dental tissue Immunomodulation Peripheral blood mononuclear cells Oral diseases Tissue regeneration

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Recombinant amelogenin regulates the bioactivity of mouse cementoblasts in vitro

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International Journal of Oral Science 2018年第2期10卷 117-126页

作者： Sema S.Hakki S.Buket Bozkurt Emre Türkay Michel Dard Nuhan Purali Werner Gotz Department of periodontology Faculty of DentistrySelcuk University Research Center of Dental Faculty Selcuk University Department of Orthodontics Oral Biology LaboratoryFaculty of DentistryUniversity of Bonn Department of periodontology and implant dentistry College of DentistryNew York University Department of Biophysics Faculty of MedicineHacettepe University

Amelogenin（AMG） is a cell adhesion molecule that has an important role in the mineralization of enamel and regulates events during dental development and root formation. The purpose of the present study was to investigate the effects of recombinant human AMG（rhAMG） on mineralized tissue-associated genes in cementoblasts. Immortalized mouse cementoblasts（OCCM-30）were treated with different concentrations（0.1, 1, 10, 100, 1 000, 10 000, 100 000 ng · mL^-1） of recombinant human AMG（rhAMG）and analyzed for proliferation, mineralization and mRNA expression of bone sialoprotein（BSP）, osteocalcin（OCN）, collagen type I（COL I）, osteopontin（OPN）, runt-related transcription factor 2（Runx2）, cementum attachment protein（CAP）, and alkaline phosphatase（ALP） genes using quantitative RT-PCR. The dose response of rhAMG was evaluated using a real-time cell *** RNA was isolated on day 3, and cell mineralization was assessed using von Kossa staining on day 8. COL I, OPN and lysosomalassociated membrane protein-1（LAMP-1）, which is a cell surface binding site for amelogenin, were evaluated using immunocytochemistry. F-actin bundles were imaged using confocal microscopy. rhAMG at a concentration of 100 000 ng · mL^-1 increased cell proliferation after 72 h compared to the other concentrations and the untreated control group. rhAMG（100 000 ng · mL^-1） upregulated BSP and OCN mRNA expression levels eightfold and fivefold, respectively. rhAMG at a concentration of 100 000 ng · mL^-1 remarkably enhanced LAMP-1 staining in cementoblasts. Increased numbers of mineralized nodules were observed at concentrations of 10 000 and 100 000 ng · mL^-1 rhAMG. The present data suggest that rhAMG is a potent regulator of gene expression in cementoblasts and support the potential application of rhAMG in therapies aimed at fast regeneration of damaged periodontal tissue.

关键词： AMG Recombinant amelogenin regulates the bioactivity of mouse cementoblasts in vitro OCN

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Microarray Analysis of the Developing Rat Mandible

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Acta Biochimica et Biophysica Sinica 2007年第6期39卷 399-405页

作者： Hideo KABURAGI Naoyuki SUGANO Maiko OSHIKAWA Ryosuke KOSHI Naoki SENDA Kazuhiro KAWAMOTO Koichi ITO Department of periodontology. Nihon University School of dentistry Tokyo 101-8310 Japan Department of periodontology. Nihon University School of dentistry Tokyo 101-8310 Japan Division of Advanced Dental Treatment Dental Research Center Nihon University School of dentistry Tokyo 101-8310 Japan Department of periodontology. Nihon University School of dentistry Tokyo 101-8310 JapanDivision of Advanced Dental Treatment Dental Research Center

To analyze the molecular events that occur in the developing mandible, we examined the expression of 8803 genes from samples taken at different time points during rat postnatal mandible development. Total RNA was extracted from the mandibles of 1-day-old, 1-week-old, and 2-week-old rats. Complementary RNA (cRNA) was synthesized from cDNA and biotinylated. Fragmented cRNA was hybridized to RGU34A GeneChip arrays. Among the 8803 genes tested, 4344 were detectable. We identified 148 genes with significantly increased expression, and 19 genes with significantly decreased expression. A comprehensive analysis appears to be an effective method of studying the complex process of development.

关键词： gene expression microarray rat mandible

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Root canal morphology and configuration of 123 maxillary second molars by means of micro-CT

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International Journal of Oral Science 2017年第1期9卷 33-37页

作者： Thomas Gerhard Wolf Frank Paqué Anja-Christin Woop Brita Willershausen Benjamín Briseno-Marroquín Department of Operative dentistry Johannes Gutenberg University Medical CenterMainzGermany division of Endodontology Department of Preventive DentistryPeriodontology and CariologyUniversity of ZurichZurichSwitzerland

The aim of this study was to investigate the root canal configuration, accessory canals and number of main foramina of 123 maxillary second molars by means of micro-computed tomography. The teeth were scanned and reproduced with 3D software imaging. The root canal configuration and number of main foramina were evaluated by means of a four-digit system. The morphological complexity of human maxillary second molars is depicted by the number of accessory and connecting canals. The most frequently observed root canal configurations in the mesiobuccal root were 2-2-2/2 （19.5%）, 2-2-1/1 （14.6%） and 2-1-1/1 （13.0%）. A 1-1-1/1 configuration was observed in 93.5% and in 96.7% in the distobuccal and palatal roots, respectively. The MB1 mot canal had one accessory canal （18.7%）, and 8.9% of the MB2 root canal had one or two accessory canals. The distobuccal （11.3%） and palatal （14.6%） root canals had at least one accessory canal, and connecting canals were observed in 16.3% of mesiobuccal roots. The MB1, MB2, distobuccal and palatal root canals had one main foramen in 99.2%, 43.1%, 98.4% and 99.2% of samples, respectively. In the mesiobuccal root, one accessory foramen was detected in 14.6%, two were detected in 7.3%, and three were detected in 5.7%. The distobuccal root showed one or two accessory foramina in 9.1% of samples. The root canal configuration of maxillary second molars is quite heterogeneous; the mesiobuccal root has predominantly two root canal entrances （58.4%, 1 in 41.1%） with one main foramen （54.4%）. Two main foramina were observed in 43.0%. Morphological variations, connecting and accessory canals were observed in all apical thirds.

关键词： accessory and connecting canals apical foramina maxillary second molar micro-CT morphology root canal configuration

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Three-dimensional analysis of the physiological foramen geometry of maxillary and mandibular molars by means of micro-CT

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International Journal of Oral Science 2017年第3期9卷 151-157页

作者： Thomas Gerhard Wolf Frank Paqué Michael Sven Patyna Brita Willershausen Benjamín Briseno-Marroquín Department of Operative dentistry University Medical Center of the Johannes Gutenberg University Mainz Department of Endodontology Division of Preventive DentistryPeriodontologyand CariologyCenter of Dental MedicineUniversity of Zürich

The aim of this study was to investigate the physiological foramen diameter, shape and distance between physiological and anatomical apex of maxillary and mandibular first and second molars. Accurate knowledge of the physiological foramina morphology; thus, inherent mechanical shaping technical hindrances, is decisive when taking the corresponding root canal final preparation decision. The morphological dimensions of a total of 1 727 physiological foramina were investigated by means of micro-computed tomography. Mean narrow and wide （to a high number, oval） diameters of the physiological foramen were 0.24, 0.22 and 0.33 mm and 0.33, 0.31 and 0.42 mm in mesiobuccal （MB）, distobuccal （DB） and palatal （P） roots in maxillary first molars; 0.24, 0.22 and 0.33 mm and 0.41, 0.33 and 0.44 in MB, DB, and P roots in maxillary second molars. Mandibular first molars showed mean narrow and wide diameters of 0.24 and 0.30 mm and of 0.39 and 0.46 mm in mesial （M） and distal （D） roots; second mandibular molars showed 0.25 and 0.31 mm and 0.47 mm in M and D roots. The mean distance between the physiological foramina and anatomical apex was 0.82, 0.81 and 1.02 mm and 0.54, 0.43 and 0.63 mm in MB, DB and P roots of the maxillary first and second molars, respectively. A mean distance of 0.95 mm （M） and 1.05 mm （D） in the first and 0.78 mm （M） and 0.81 mm （D） in the second mandibular molars was observed. Based on the results obtained, assumable recommendations for final preparation size of the physiological foramen were calculated. However, when taking into consideration, the resulting standard deviations of marginal errors must be cautiously considered when taking a final decision in clinical endodontic treatment.

关键词： apical constriction final apical file maxillary and mandibular molars morphology micro-computed tomography physiological foramen

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Replacing Missing Teeth with Dental implants in Pubescent Patients—A Case Report

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Open Journal of Pediatrics 2015年第3期5卷 207-212页

作者： Wendy C. W. Wang Loana Tovar Suinaga Klenise S. Paranhos Sang-Choon Cho Ashman Department of periodontology and implant dentistry New York University College of Dentistry New York USA

Tooth loss due to traumatic dental injury or congenital absence can cause functional and social- psychological consequences in youth. Pubescent children with missing teeth are often targets for school bullying. The treatment modality chosen can impact their well-being during their formative years. Despite the high success rate in adult patients, implant placement in young patients is not common due to its ankylosed nature and concerns with possible infra-occlusion in the future. However, skeletal growth and remodeling is a continuous process throughout life and postponement of dental implant placement does not necessary prevent future complication or need for replacement. Dental implant placement should be considered as a viable treatment option for pubescent patients if all other conventional alternatives fail to alleviate patients’ concerns both functionally and psychologically. This case report evaluates the considerations required to place dental implants in pubescent patients, as well as its advantages and disadvantages.

关键词： Dental implants Pubescent Social-Psychological Bullying

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Scutellarin attenuates endothelium-dependent aasodilation impairment induced by hypoxia reoxygenation, through regulating the PKG signaling pathway in rat coronary artery

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Chinese Journal of Natural Medicines 2015年第4期13卷 264-273页

作者： CHEN Ya-Juan WANG Lei ZHOU Guang-Yu YU Xian-Lun ZHANG Yong-Hui HU Na LI Qing-Qing CHEN Chen QING Chen LIU Ying-Ting YANG Wei-Min School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products Kunming Medical University Zhaotong Institute of Tianma Department of periodontology and implant dentistry The First People's Hospital of Yun-Nan Province Kunhua Hospital Affiliated to Kunming University of Science and Technology

Scutellarin(SCU), a flavonoid from a traditional Chinese medicinal plant. Our previous study has demonstrated that SCU relaxes mouse aortic arteries mainly in an endothelium-depend-ent manner. In the present study, we investigated the vasoprotective effects of SCU against HR-induced endothelial dysfunction(ED) in isolated rat CA and the possible mechanisms involving cyclic guanosine monophosphate(c GMP) dependent protein kinase(PKG). The isolated endothelium-intact and endothelium-denuded rat CA rings were treated with HR injury. Evaluation of endothelium-dependent and-independent vasodilation relaxation of the CA rings were performed using wire myography and the protein expressions were assayed by Western blotting. SCU(10–1 000 μmol·L-1) could relax the endothelium-intact CA rings but not endothelium-denuded ones. In the intact CA rings, the PKG inhibitor, Rp-8-Br-c GMPS(PKGI-rp, 4 μmol·L-1), significantly blocked SCU(10–1 000 μmol·L-1)-induced relaxation. The NO synthase(NOS) inhibitor, NO-nitro-L-arginine methylester(L-NAME, 100 μmol·L-1), did not significantly change the effects of SCU(10–1 000 μmol·L-1). HR treatment significantly impaired ACh-induced relaxation, which was reversed by pre-incubation with SCU(500 μmol·L-1), while HR treatment did not altered NTG-induced vasodilation. PKGI-rp(4 μmol·L-1) blocked the protective effects of SCU in HR-treated CA rings. Additionally, HR treatment reduced phosphorylated vasodilator-stimulated phosphoprotein(p-VASP,phosphorylated product of PKG), which was reversed by SCU pre-incubation, suggesting that SCU activated PKG phosphorylation against HR injury. SCU induces CA vasodilation in an endothelium-dependent manner to and repairs HR-induced impairment via activation of PKG signaling pathway.

关键词： Scutellarin Endothelium-dependent vasodilation Hypoxia reoxygenation c GMP-dependent protein kinase Rat Coronary artery

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Ectomesenchymal chondromyxoid tumor: a comprehensive updated review of the literature and case report

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International Journal of Oral Science 2018年第1期10卷 7-13页

作者： Astrid Truschnegg Stephan Acham Lumnije Kqiku Norbert Jakse Alfred Beham Department of Dental Medicine and Oral Health Division of Oral Surgery and OrthodonticsMedical University Graz Department of Dental Medicine and Oral Health Division of Preventive an Operative DentistryEndodonticsPeriodontologyProsthodonticsRestorative Dentistry and ImplantologyMedical University Graz IMAH Institute of Morphological Analytics and Human Genetics

Prompted by a unique case of an ectomesenchymal chondromyxoid tumor(ECT) of the palate in a 54-year-old female, we reviewed the English and German literature on this entity until the end of 2016 using Pub Med. The search produced 74 lingual cases with a nearly equal sex distribution and a mean age of 39.3 years, and two extra-lingual cases sharing histological and immunohistological features including nodular growth, round, fusiform or spindle-shaped cellular architecture, and chondromyxoid *** showed the majority of cases to be positive for glial fibrillary acidic protein(GFAP), S-100 protein,glycoprotein CD57, pancytokeratin (AE1/AE3), and smooth muscle actin(SMA); in isolated cases there was molecular-genetic rearrangement or gain of Ewing sarcoma breakpoint region 1 (EWSR1) but no rearrangement of pleomorphic adenoma gene 1 (PLAG1). At present, ectomesenchymal cells that migrate from the neural crest are considered to play a pivotal role in tumor *** cases had a benign course, although there were three recurrences. Because of the rarity of this tumor and the need for differential diagnostic differentiation from myoepithelioma and pleomorphic adenoma, both oral surgeons and pathologists should be aware of this entity.

关键词： ANTERIOR TONGUE SOFT-TISSUE MYOEPITHELIAL NEOPLASMS

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Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism

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Bone Research 2017年第1期5卷 49-62页

作者： Jin Zhang Paloma Valverde Xiaofang Zhu Dana Murray Yuwei Wu Liming Yu Hua Jiang Michel M Dard Jin Huang Zhiwei Xu Qisheng Tu Jake Chen division of Oral Biology Department of PeriodontologyTufts University School of Dental MedicineBostonMA 02111USA Department of Anatomy Research Center for Integrative MedicineGuangzheu University of Chinese MedicineGuangzhouGuangdong Province 510405China Department of Sciences Center for Sciences and Biomedical EngineeringBostonMA 02115USA Department of periodontology and implant dentistry New York University College of DentistryNew YorkNY 10010USA Department of Anatomy and Cell Biology Tufts University School of Medicine and Sackler School of Graduate Biomedical SciencesBostonMA 02111USA

Irisin is a polypeptide hormone derived from the proteolytic cleavage of fibronectin-type III domain- containing 5 （FNDC5） protein. Once released to circulation upon exercise or cold exposure, irisin stimulates browning of white adipose tissue （WAT） and uncoupling protein I （UCP1） expression, leading to an increase in total body energy expenditure by augmented UCPl-mediated thermogenesis. It is currently unknown whether irisin is secreted by bone upon exercise or whether it regulates bone metabolism in vivo. In this study, we found that 2 weeks of voluntary wheel-running exercise induced high levels of FNDC5 messenger RNA as well as FNDC5/irisin protein expression in murine bone tissues. Increased immunoreactivity due to exercise-induced FNDC5/irisin expression was detected in different regions of exercised femoral bones, including growth plate, trabecular bone, cortical bone, articular cartilage, and bone-tendon interface. Exercise also increased expression of osteogenic markers in bone and that of UCP1 in WAT, and led to bodyweight loss. Irisin intraperitoneal （IP） administration resulted in increased trabecular and cortical bone thickness and osteoblasts numbers, and concurrently induced UCP1 expression in subcutaneous WAT. Lentiviral FNDC5 IP administration increased cortical bone thickness. In vitro studies in bone cells revealed irisin increases osteoblastogenesis and mineralization, and inhibits receptor activator of nuclear factor-kB ligand （RANKL）- induced osteoclastogenesis. Taken together, our findings show that voluntary exercise increases irisin production in bone, and that an increase in circulating irisin levels enhances osteogenesis in mice.

关键词： Exercise-induced irisin in bone and systemic irisin administration reveal new regulatory mechanisms of bone metabolism bone

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