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Characterization of the osteogenic potential of mesenchymal stem cells from human periodontal ligament based on cell surface markers

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International Journal of Oral Science 2015年第4期7卷 213-219页

作者： Ruth Alvarez Hye-Lim Lee Cun-Yu Wang Christine Hong Division of Oral Biology and Medicine School of DentistryUniversity of California at Los Angeles section of orthodontics School of DentistryUniversity of California at Los Angeles

Mesenchymal stem cell （MSC）-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with high capacity to differentiate into appropriate tissues. The utilization of stem cell surface antigens provides a means to identify MSCs from various tissues. However, few surface markers that consistently isolate highly regenerative MSCs have been validated, making it challenging for routine clinical applications and making it all the more imperative to identify reliable surface markers. In this study, we used three surface marker combinations： CD51/CD140a, CD271, and STRO-1/CD146 for the isolation of homogenous populations of dental mesenchymal stem cells （DMSCs） from heterogeneous periodontal ligament cells （PDLCs）. Fluorescence-activated cell sorting analysis revealed that 24% of PDLCs were CD51＋/CD140a＋, 0.8% were CD271＋, and 2.4% were STRO-1＋/CD146＋. Sorted cell populations were further assessed for their multipotent properties by inducing osteogenic and chondrogenic differentiation. All three subsets of isolated DMSCs exhibited differentiation capacity into osteogenic and chondrogenic lineages but with varying degrees. CD271＋ DMSCs demonstrated the greatest osteogenic potential with strong induction of osteogenic markers such as DLX5, RUNX2, and BGLAP. Our study provides evidence that surface marker combinations used in this study are sufficient markers for the isolation of DMSCs from PDLCs. These results provide important insight into using specific surface markers for identifying homogenous populations of DMSCs for their improved utilization in regenerative medicine.

关键词： cell surface markers dental mesenchymal stem cells periodontal ligament

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Single CD271 marker isolates mesenchymal stem cells from human dental pulp

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International Journal of Oral Science 2015年第4期7卷 205-212页

作者： Ruth Alvarez Hye-Lim Lee Christine Hong Cun-Yu Wang Division of Oral Biology and Medicine School of DentistryUniversity of California at Los Angeles section of orthodontics School of DentistryUniversity of California at Los Angeles Department of Bioengineering Henry Samueli School of Engineering and Applied ScienceUniversity of California at Los Angeles

Mesenchymal stem cells （MSCs） are a promising tool in regenerative medicine due to their capacity to differentiate into multiple lineages. In addition to MSCs isolated from bone marrow （BMSCs）, adult MSCs are isolated from craniofacial tissues including dental pulp tissues （DPs） using various stem cell surface markers. However, there has been a lack of consensus on a set of surface makers that are reproducibly effective at isolating putative multipotent dental mesenchymal stem cel^s （~M^Cs）. II1 ~his stucly, we used clif^et（~nt combinations of surface markers （CD51/CD140a, CD271, and STRO-1/CD146） to isolate homogeneous populations of DMSCs from heterogeneous dental pulp cells （DPCs） obtained from DP and compared their capacity to undergo multilineage differentiation. Fluorescence-activated cell sorting revealed that 27.3% of DPCs were CD51＋/CD140a＋, 10.6% were CD271＋, and 0.3% were STRO-1＋/CD146＋. Under odontogenic conditions, all three subsets of isolated DMSCs exhibited differentiation capacity into odontogenic lineages. Among these isolated subsets of DMSCs, CD271＋ DMSCs demonstrated the greatest odontogenic potential. While all three combinations of surface markers in this study successfully isolated DMSCs from DPCs, the single CD271 marker presents the most effective stem cell surface marker for identification of DMSCs with high odontogenic potential. Isolated CD271＋ DMSCs could potentially be utilized for future clinical applications in dentistry and regenerative medicine.

关键词： dental mesenchymal stem cells odontogenic differentiation cell surface markers dental pulp fluorescence-activated cellsorting

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KDM6B epigenetically regulates odontogenic differentiation of dental mesenchymal stem cells

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International Journal of Oral Science 2013年第4期5卷 200-205页

作者： Juan Xu Bo Yu Christine Hong Cun-Yu Wang Department of Stomatology Chinese People's Liberation Army General Hospital Division of Oral Biology and Medicine School of DentistryUniversity of California section of orthodontics School of DentistryUniversity of California Department of Bioengineering Henry Samueli School of Engineering and Applied ScienceUniversity of California

Mesenchymal stem cells （MSCs） have been identified and isolated from dental tissues, including stem cells from apical papilla, which demonstrated the ability to differentiate into dentin-forming odontoblasts. The histone demethylase KDM6B （also known as JMJD3） was shown to play a key role in promoting osteogenic commitment by removing epigenetic marks H3K27me3 from the promoters of osteogenic genes. Whether KDM6B is involved in odontogenic differentiation of dental MSCs, however, is not known. Here, we explored the role of KDM6B in dental MSC fate determination into the odontogenic lineage. Using shRNA-expressing lentivirus, we performed KDM6B knockdown in dental MSCs and observed that KDM6B depletion leads to a significant reduction in alkaline phosphate （ALP） activity and in formation of mineralized nodules assessed by Alizarin Red staining. Additionally, mRNA expression of odontogenic marker gene SP7 （osterix, OSX）, as well as extracellular matrix genes BGLAP （osteoclacin, OCN） and SPP1 （osteopontin, OPN）, was suppressed by KDM6B depletion. When KDM6B was overexpressed in KDM6B-knockdown MSCs, odontogenic differentiation was restored, further confirming the facilitating role of KDM6B in odontogenic commitment. Mechanistically, KDM6B was recruited to bone morphogenic protein 2 （BMP2） promoters and the subsequent removal of silencing H3K27me3 marks led to the activation of this odontogenic master transcription gene. Taken together, our results demonstrated the critical role of a histone demethylase in the epigenetic regulation of odontogenic differentiation of dental MSCs. KDM6B may present as a potential therapeutic target in the regeneration of tooth structures and the repair of craniofacial defects.

关键词： bone morphogenic protein dental mesenchymal stem cell epigenetics KDM6B odontogenic differentiation

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Suicide signaling by GSDMA:a single-molecule mechanism for recognition and defense against SpeB-expressing GAS

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Signal Transduction and Targeted Therapy 2022年第6期7卷 1870-1871页

作者： Judit Symmank Collin Jacobs Ulrike Schulze-Späte Department of orthodontics University Hospital JenaLeutragraben 307743 JenaGermany section of Geriodontics Department of Conservative Dentistry and PeriodonticsUniversity Hospital JenaAn der Alten Post 407743 JenaGermany

In a recent article published in Nature,1 Deng and colleagues uncovered a single-molecule mechanism for protection against the harmful human microbial pathogen Streptococcus *** Gram-positive Group A Streptococci(GAS)are responsible for a variety of acute infections ranging from noninvasive,mildly progressive to invasive infectious diseases with high mortality *** virulence factors thereby condition the invasion of the bloodstream and soft tissue,leading to invasive systemic dissemination.2 Deng et *** GSDMA not only as a sensor for intracellular streptopain(SpeB),an important GAS virulence factor,but also as an effector protein for host epithelial cell pyroptosis.

关键词： invasion mortality acute

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Histone methyltransferases and demethylases:regulators in balancing osteogenic and adipogenic differentiation of mesenchymal stem cells

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International Journal of Oral Science 2015年第4期7卷 197-204页

作者： Peng Deng Qian-Ming Chen Christine Hong Cun-Yu Wang Division of Oral Biology and Medicine School of DentistryUniversity of California at Los Angeles State Key Laboratory of Oral Disease West China School of StomatologySichuan University section of orthodontics School of DentistryUniversity of California at Los Angeles Department of Bioengineering Henry Samueli School of Engineering and Applied ScienceUniversity of California at Los Angeles

Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su（var）3-9, enhancer-of-zeste, trithorax （SET） domain-containing family and the Jumonji C （JmjC） domain-containing family represent the major histone lysine methyltransferases （KMTs） and histone lysine demethylases （KDMs）, respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containine KMTs and JmiC domain-containinlz KDMs balance the osteogenic and adipogenic differentiation of MSCs.

关键词： adipogenesis histone methylation histone lysine methyltransferase histone lysine demethylase mesenchymal stemcells osteogenesis

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TRAIL Immunolocalisation in the Rat Periodontal Ligament during Experimental Tooth Movement. A Preliminary Study

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Open Journal of Apoptosis 2013年第3期2卷 31-36页

作者： Carla Loreto Giuseppe Musumeci Sergio Castorina Jessica Valentino Salvatore Giunta Rosalia Leonardi Department of Bio-Medical Sciences Anatomy and Histology Section University of Catania Catania Italy Department of orthodontics University of Catania Catania Italy

The aim of this study was to evaluate immunohistochemically TRAIL (TNF-Related Apoptosis Inducing Ligand) expression in the periodontal ligament of rats’ molars considering its distribution pattern in the tension and compressive regions of ligament during orthodontic movement. Sixteen Sprague-Dawley rats, weighing between 120 and 200 gwere used in the present study. Tooth movement was induced by placing elastic bands between the maxillary first and second molars. The elastic bands were left in place for 12 (time T1) and 24 (time T2) hours. After rats’ euthanasia, maxillae were dissected free and the sections were exposed to a primary rabbit polyclonal anti-TRAIL anti-body. The staining status was identified as either negative or positive by using 3,3’-diaminobenzidine (DAB) to develop the immunoreaction. Data were analyzed using ANOVA test and a post-hoc Dunn’s Multiple Comparison test. P-values of less than 0.05 were considered statistically significant. The staining for TRAIL in the tension side appeared darker (intensity of staining = 2) than in the compressive side (intensity of staining = 1) 12 h after the tooth movement. The stainings of both sides of PDL were observed to be up-regulated 24 h after the application of the force (tension side = 3, compression side = 2;P 0.05). TRAIL is expressed in the periodontal ligament of rats’ molars during experimental tooth movement both in the compression and in the tension sides. The latter showed the highest amount of TRAIL immunolabeling.

关键词： Immunohistochemistry Pperiodontal Ligament Tooth Movement Trail

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Recently highlighted nutraceuticals for preventive management of osteoarthritis

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World Journal of Orthopedics 2018年第11期9卷 255-261页

作者： Silvia Ravalli Marta Anna Szychlinska Rosalia Maria Leonardi Giuseppe Musumeci Department of Biomedical and Biotechnological Sciences Human Anatomy and Histology SectionSchool of MedicineUniversity of Catania Department of orthodontics Policlinico Universitario "Vittorio Emanuele"University of Catania

Osteoarthritis(OA) is a chronic degenerative disease of articular cartilage with limited treatment options. This reality encourages clinicians to suggest preventive measures to delay and contain the outbreak of the pathological conditions. Articular cartilage and synovium suffering from OA are characterised by an inflammatory state and by significant oxidative stress,responsible for pain,swelling and loss of mobility in the advanced stages. This review will focus on the ability of olive oil to exert positive effects on the entire joint to reduce pro-inflammatory cytokine release and increase lubricin synthesis,olive leaf extract,since it maintains lubrication by stimulating high molecular weight hyaluronan synthesis in synovial cells,curcumin,which delays the start of pathological cartilage breakdown,sanguinarine,which downregulates catabolic proteases,vitamin D for its capacity to influence the oxidative and proinflammatory environment,and carnosic acid as an inducer of heme oxygenase-1,which helps preserve cartilage degeneration. These molecules,considered as natural dietary supplements,appear like a cuttingedge answer to this tough health problem,playing a major role in controlling homeostatic balance loss and slowing down the pathology progression. Natural or food-derived molecules that are able to exert potential therapeutic effects are known as "nutraceutical",resulting from the combination of the words "nutrition" and "pharmaceutical". These compounds have gained popularity due to their easy availability,which represents a huge advantage for food and pharmaceutical industries. In addition,the chronic nature of OA implies the use of pharmacological compounds with proven longterm safety,especially because current treatments like nonsteroidal anti-inflammatory drugs and analgesicsimprove pain relief but have no effect on degenerative progression and can also cause serious side effects.

关键词： Osteoarthritis Nutraceuticals Prevention Diet Inflammation Oxidative stress

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Mechanical properties of nickel-titanium archwire used in the final treatment phase of Tip-Edge Plus technique： an in vitro study

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Chinese Medical Journal 2013年第1期126卷 135-139页

作者： SHEN Xiao SUN Xin-hua TIAN Hua ZHANG Chun-bo YAN Kuo GUO Yong-liang Department of orthodontics Faculty of Stomatology JilinUniversity Changchun Jilin 130021 China Center of Analysis and Testing Faculty of Materials Science and Engineering Harbin Institute of Technology Harbin Heilongjiang 150001 China

Background As the only active component in final treatment phase of Tip-Edge Plus technique, the activation of nickel-titanium orthodontic archwires is one of the factors that affect the torque expression. It is necessary to evaluate the mechanical properties of the nickel-titanium wire used in the final treatment phase in simulated oral environments to forecast the treatment outcomes. Methods The mechanical properties of 171 thermal nickel-titanium wires of 0.35 mm （0.014-in） in diameters with different deflection of 40 mm in length were investigated with three-point bending test. The samples were divided into 2 groups： as-received and bended groups. In the bended group, samples were divided into 7 subgroups according to the amounts of deflection and named by the canine angulations （-25~, -19~, -13~, -7~, -1~, ＋5~, ＋11~）. The deflection of wires was made by inserting the wires into the deep tunnel of Tip-Edge Plus brackets positioned in plaster casts with different canine angulations to mimic the use of nickel-titanium wires in the final treatment phase. Immersed the bended group in artificial saliva （pH 6.8） and preserved at 37.0~C. Eight durations of incubation were tested： 1 to 8 weeks. Three analogous samples of each group and subgroups were tested per week. Stiffness （YS：E） and the load-deflection characteristics of unloading plateau section were obtained. Results Significant changes in specific mechanical properties were observed in long-term immersed and large deflected wires compared with as-received groups. Both immersion time and deflection affected the mechanical properties of wires in the simulated oral environment, and the two factors had synergistic effect. In groups -25~, -19~ and -13~, stiffness （YS：E） increased then decreased and average plateau force and ratio of variance decreased then increased correspondingly at specific time. Conclusions In the final treatment phase of Tip-Edge Plus technique, the mechanical properties of nickel-titanium wire

关键词： Tip-Edge Plus archwires nickel-titanium three-point bending test crown angulation

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Cone-Beam Computed Tomography Evaluation of the Positions of Unerupted Maxillary Canines with Incisor Root Resorption

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Open Journal of Stomatology 2017年第3期7卷 169-179页

作者： Sachio Tamaoki Hiroyuki Ishikawa Kyoko Oka Masao Ozaki Akiko Abe Shunsuke Takata Shozaburo Hata section of orthodontics Department of Oral Growth & Development Division of Clinical Dentistry Fukuoka Dental College Fu-kuoka Japan Fukuoka Dental College Fukuoka Japan section of Pediatric Dentistry Department of Oral Growth & Development Division of Clinical Dentistry Fukuoka Dental College Fukuoka Japan

Purpose: To establish a new coordinate system using the incisive canal and incisive foramen in cases confirmed to have root resorption in the maxillary incisor region by cone beam computed tomography (CBCT) to investigate the positions of the central and lateral incisor roots and erupting maxillary canine tooth crowns in the horizontal plane. Methods: Nine patients (two males;mean age: 10.5 years old) with suspected incisor root resorption due to erupting maxillary canines on panoramic X-ray images and in whom incisor root resorption was confirmed on CBCT images were evaluated. A control group of 12 patients with a supernumerary tooth on one side (three males;mean age: 8.6 years old) was also examined. X, Y, and Z-axes were defined, and the positions of the centers of the central incisor root (U1) and lateral incisor root (U2) and the canine cusp (U3) were examined, along with alveolar process width and length. Results: In the control group, U1, U2, and U3 were located within a certain range without overlap, while, in the incisor root resorption group, U3 overlapped with U1 and U2 and tended to deviate centrally. U2 tended to be located further posteriorly than U3. The anteroposterior diameter of the alveolar process was 1.2 mm shorter in the incisor root resorption group (p < 0.05). Conclusions: The risk of incisor root resorption accompanying canine eruption can be evaluated early by investigating the canine position on a horizontal plane established on the upper anterior tooth dentition CT images with a coordinate system using the incisive canal and incisive foramen.

关键词： CBCT Incisor Root Resorption Maxillary Canine Incisive Canal Alveolar Process

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Growth differentiation factor 6,a repressive target of EZH2,promotes the commitment of human embryonic stem cells to mesenchymal stem cells

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Bone Research 2020年第4期8卷 439-446页

作者： Pend Deng Yongxin Yu Christine Hong Cun-Yu Wang Laboratory of Molecular Signaling Division of Oral Biology and MedicineSchool of DentistryUniversity of California Los AngelesLos AngelesCA 90095USA section of orthodontics Division of Growth and DevelopmentSchool of DentistryUniversity of California Los AngelesLos AngelesCA 90095USA Jonsson Comprehensive Cancer Center Broad Stem Cell Research Institute and Department of BioengineeringHenry Samueli School of Engineering and Applied ScienceUniversity of California Los AngelesLos AngelesCA 90095USA

Mesenchymal stem cells(MSCs)derived from human embryonic stem cells(hESCs)have significant potential for cell-mediated bone *** recent study revealed that inhibiting the epigenetic regulator EZH2 plays a key role in promoting the mesodermal differentiation of *** this study,an epigenome-wide analysis of hESCs and MSCs revealed that growth differentiation factor 6(GDF6),which is involved in bone formation,was the most upregulated gene associated with MSCs compared to ***,we identified GDF6 as a repressive target of EZH2 and found that ectopic GDF6 selectively promoted hESC differentiation towards the mesodermal lineage and enriched the MSC *** results provide molecular insights governing the mesenchymal commitment of hESCs and identify an inducing factor that offers strong promise for the future of regenerative medicine.

关键词： EZH2 mesenchymal inhibiting

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