Tokyo Dental College
Research Project

Asian Rising Stars Symposium 2023
July 29, 2023

Well-being Society Achieved by Maintaining and
Improving Oral-Maxillofacial Function at Every Stage of Life
(Well-being Project)

Program and Abstracts

Saturday, July 29
Tokyo Dental College Research Project
Asian Rising Stars Symposium 2023

Program
13:00-13:05：Opening Remarks
Tatsuya Ichinohe (Dean, Tokyo Dental College)
Session Ⅰ Moderator: Masahito Yamamoto (Department of Anatomy, Tokyo Dental College)
Toshihide Mizoguchi (Oral Health Science Center, Tokyo Dental College)
13:05-13:35：Lecture Ⅰ
Regenerative potentials of the dental pulp stem cells-derived small extracellular
vesiclesSheng-Wei Feng (School of Dentistry, College of Oral Medicine, Taipei Medical
University)
13:35-14:05：Lecture Ⅱ
Schnurri-3: an osteogenesis-plus regulator
Ren Xu (School of Medicine, Xiamen University)
Session Ⅱ Moderator: Tomoko Someya (Department of Dental Materials Science, Tokyo Dental
College)
Natsuko Aida (Department of Biochemistry, Tokyo Dental College)
14:05-14:35：Lecture Ⅲ
Improved enamel acid resistance by acidulated phosphate sodium
monofluorophosphate solution
Ryouichi Satou (Department of Epidemiology and Public Health, Tokyo Dental
College)
14:35-15:05：Lecture Ⅳ
Cell-laden microspheres and oxygenation materials applied in endodontic
regeneration
Li Xie (State Key Laboratory of Oral Disease, West China College of Stomatology,
Sichuan University)
15:05-15:20：Coffee Break (15 min)Session Ⅲ Moderator: Yoshiyuki Shibukawa (Department of Physiology, Tokyo Dental College)
15:20-16:00：Keynote Lecture
Pathophysiology of sleep bruxism
Takafumi Kato (Department of Oral Physiology, Osaka University Graduate Schoolof Dentistry)
Session Ⅳ Moderator: Tatsukuni Ohno (Oral Health Science Center, Tokyo Dental College)
Takehito Ouchi (Department of Physiology, Tokyo Dental College）
16:00-16:30：Lecture Ⅴ
The effect of cigarette smoke on interaction of host cells with periodontal pathogen
and periodontal healing
Kentaro Imamura (Department of Periodontology, Tokyo Dental College)1

16:30-17:00：Lecture Ⅵ
POMC neuron targeting peptide regulates energy homeostasis
Ki Woo Kim (Division of Physiology, Department of Oral Biology, Yonsei University
College of Dentistry)
17:00-17:05：Closing Remarks
Akira Yamaguchi (Advisor, Tokyo Dental College Research Well-being Project)2

[Lecture Ⅰ]
Regenerative potentials of the dental pulp stem cells-derived small
extracellular vesicles
Sheng-Wei Feng, DDS, MS, PhD
Director & Professor
School of Dentistry,
College of Oral Medicine, Taipei Medical University
Accumulating evidence indicates that the therapeutic effect of mesenchymal stem cells (MSCs) mainly
depends on their paracrine action. MSCs-derived small extracellular vesicles (exosomes, Exo) are key
mediators in intercellular communications and microenvironment maintenance by delivering
therapeutic protein and miRNA. However, the research field suffers from inconsistencies regarding
Exo's purification, characterization, and bioactivity at the molecular, cellular, and tissue levels.
Moreover, the underlying mechanisms by which Exo regenerates tissues and modulates immune
response have not been fully elucidated. There are several methods for the isolation of exosome
samples now. Ultracentrifugation is the most used technique, but repeated ultracentrifugation can
destroy exosome structure and biological integrity. We evaluated the isolation of exosomes from dental
pulp mesenchymal stem cells using ultracentrifugation and ultrafiltration combined with size
exclusion chromatography. We directly compared the ability of the two methods to isolate exosomes,
comparing and analyzing their exosome characterization, standard quantification, characterization,and proteomic analysis in an integrated and systematic manner. Both ultracentrifugation andultrafiltration combined with size exclusion chromatography successfully isolated exosomes.
Ultrafiltration combined with size exclusion chromatography isolates exosome yields higher, and thesample distribution particles have more average size, making it more suitable for large-scale research
applications. We also further evaluate and compare the two different isolation methods of exosomes
for periodontal ligament stem cells (PDLSCs) morphology, growth, cell growth cycle, various
differentiation abilities, various gene expression, and possible discussion of message transmission
paths.

3

Curriculum Vitae
2004
DDS, Dentistry, Taipei Medical University, Taipei, Taiwan
2007
MS, Dentistry, Taipei Medical University, Taipei, Taiwan
2014
PhD, Dentistry, Taipei Medical University, Taipei, Taiwan
2016-2019 Assistant Professor, School of Oral Hygiene, College of Oral Medicine, Taipei Medical
University
2019-2022 Associate Professor, School of Dentistry, College of Oral Medicine, Taipei Medical
University
2020.08- Director, School of Dentistry, College of Oral Medicine, Taipei Medical University
2022.08- Professor, School of Dentistry, College of Oral Medicine, Taipei Medical University
Honors2021 Taiwan Association for Dental Sciences Academic Award
Research Fields of Interest
Oral tissue-derived mesenchymal stem cells, regenerative medicine, tissue engineering
Selected Publications
1.
Huang WH, Hung CY, Chiang PC, Lee H, Lin IT, Lai PC, Chan YH, Feng SW*.
Physicochemical Characterization, Biocompatibility, and Antibacterial Properties of
CMC/PVA/Calendula officinalis Films for Biomedical Applications. Polymers (Basel). 2023
Mar 14;15(6):1454. (5-Year Impact Factor：5.063, POLYMER SCIENCE 16/90=17.8%)
2.
Chan YH, Ho KN, Lee YC, Chou MJ, Lew WZ, Huang HM, Lai PC, Feng SW*. Melatoninenhances osteogenic differentiation of dental pulp mesenchymal stem cells by regulating
MAPK pathways and promotes the efficiency of bone regeneration in calvarial bone defects.
Stem Cell Res Ther. 2022 Feb 19;13(1):73. (5-year IF: 8.393, CELL & TISSUEENGINEERING 6/31=17.74 %)3.
Chan YH, Lee YC, Hung CY, Yang PJ, Lai PC, Feng SW*. Three-dimensional Spheroid
Culture Enhances Multipotent Differentiation and Stemness Capacities of Human Dental Pulpderived Mesenchyma Stem Cells by Modulating MAPK and NF-kB Signaling Pathways. Stem
Cell Rev Rep. 2021 Apr 24. Online ahead of print. (IF: 6.692, MEDICINE, RESEARCH &EXPERIMENTAL 34/139=24.1 %)4.
Feng SW*, Su YH, Lin YK, Wu YC, Huang YH, Yang FH, Chiang HJ, Yen Y, Wang PD.
Small blood stem cells for enhancing early osseointegration formation on dental implants: ahuman phase I safety study. Stem Cell Res Ther. 2021 Jul 2;12(1):380. (5-year IF: 8.393,
CELL & TISSUE ENGINEERING 6/31=17.74 %)5.
Lew WZ, Feng SW, Lee SY, Huang HM. The Review of Bioeffects of Static Magnetic Fields
on the Oral Tissue-Derived Cells and Its Application in Regenerative Medicine. Cells. 2021
Oct 5;10(10):2662. (5-year IF: 7.677, CELL BIOLOGY 51/194=26.03%)
6.
Shiu ST, Lee WF, Chen SM, Hao LT, Hung YT, Lai PC, Feng SW*. Effect of Different Bone
Grafting Materials and Mesenchymal Stem Cells on Bone Regeneration: A Micro-Computed
Tomography and Histomorphometric Study in a Rabbit Calvarial Defect Model. Int J Mol Sci.
2021 Jul 28;22(15):8101. (5-year IF: 6.132, BIOCHEMISTRY & MOLECULAR BIOLOGY
67/297=22.6%)

4

[Lecture Ⅱ]
Schnurri-3: an osteogenesis-plus regulator
Ren Xu, PhD
Professor of School of Medicine, Xiamen University
Director of Fujian Provincial Key Laboratory of Organ and Tissue Regeneration
Director of the First Affiliated Hospital of
Xiamen University-ICMRS (International Chinese Musculoskeletal
Research Society) Collaborating Center
Abstract:
The skeleton has been suggested to function as an endocrine organ controlling whole organism energybalance, however the regulators of this effect and their potential clinical utility remain unclear. Here,
we utilize mice with augmented osteoblast activity, Schnurri-3-/- (Shn3-/- mice), to probe generalrelationships between osteogenesis and metabolic syndrome. At overnutrition condition, Shn3-/- micedisplay obesity resistance with improved glucose homeostasis and insulin sensitivity regulated bybrowning of white adipose tissue (WAT). Conditional deletion of Shn3 in osteoblasts (Shn3Osx mice)but not adipocytes (Shn3Adq mice) not only recapitulated the phenotype against obesity seen in Shn3-/mice but also activated browning of perivascular adipose tissue (PVAT) to alleviate cardiovascularpathological features in the atherosclerosis model, indicating that the role of Shn3 in regulating
metabolic syndrome is driven by the skeleton. Through in vitro co-culture assay and in vivo fat-padtransplantation assay, we confirmed that the “osteokines” secreted by activated osteoblasts lacking
Shn3 expression indeed promoted WAT browning. Among them, we identified that SLIT2 is a Shn3regulated factor secreted by osteoblasts that enhances WAT browning, with osteoblasts serving as the
major source of systemic circulating SLIT2. Therapeutically, a bone-targeting AAV treatment
suppressing Shn3 expression not only increased bone mass but also rescued both obesity andatherosclerosis phenotypes at pathological conditions, which potentially avoided the cardiovascularrisk of anti-sclerostin antibodies utilized in osteoporosis. Collectively, our findings established a novel
link in bone-fat axis through SHN3 regulated production of SLIT2 in osteoblasts, offering a plausible
strategy in treating both bone loss and metabolic syndrome.

5Curriculum Vitae
2019-Present
Professor
2014-2019
Postdoc
2013-2014
Research Fellow
2008-2013

PhD

School of Medicine, Xiamen University, China
Weill Cornell Medicine, Cornell University, US
Department of Orthopaedic Surgery, Tokyo
Medical and Dental University, JapanTokyo Medical and Dental University, Japan

Research Fields of Interest
1. The role of nerve/vascular system in bone degenerative diseases
2. Identification of skeletal stem cell/precursor cell subtypes
3. The endocrine function of bone forming cells
Selected Honors
1. 2019: AIMM-ASBMR John Haddad Young Investigator Award
2. 2018: ASBMR Annual Meeting Young Investigator Award
3. 2017: Webster Jee Young Investigator Award (ICMRS)
Selected Publications
1. Xu R, Yallowitz A, Qin A, Wu Z, Shin D, Kim J, Debnath S, Ji G, Bostrom M, Yang X, Zhang
C, Dong H, Kermani P, Lalani S, Li N, Liu Y, Poulos M, Wach A, Zhang Y, Inoue K, Lorenzo
A, Zhao B, Butler J, Shim J, Glimcher L* and Greenblatt MB*. Targeting skeletal endothelium
to ameliorate bone loss. Nature Medicine. 2018;24(6):823-833.
2. Fukuda T#, Takeda S*#, Xu R#, Ochi H, Sunamura S, Sato T, Shibata S, Yoshida Y, Gu Z, Kimura
A, Ma C, Xu C, Bando W, Fujita K, Shinomiya K, Hirai T, Asou Y, Enomoto M, Okano H,
Okawa A, Itoh H. Sema3A regulates bone-mass accrual through sensory innervations. Nature.
2013;497(7450):490-493. (#: Co-first)
3. Xu R, Zhang C, Shin DY, Kim JM, Lalani S, Li N, Yang YS, Liu Y, Eiseman M, Davis RJ, Shim
JH*, Greenblatt MB*. c-Jun N-terminal kinases (JNKs) are critical mediators of osteoblast
activity in vivo. Journal of Bone and Mineral Research. 2017;32(9):1811-1815.
4. Li N, InoueK, Sun J, Niu Y, Lalani S, Yallowitz A, Yang X, Zhang C, Shen R, Zhao B, Xu R*,
Greenblatt MB. Osteoclasts are not a source of SLIT3. Bone Research. 2020;8:11. (*:Corresponding)
5. Zhou T, Chen Y, Liao Z, Zhang L, Su D, Li Z, Yang X, Ke X, Liu H, Chen Y, Weng R, Shen H,
Xu C, Wan Y, Xu R*, Su P*. Spatiotemporal Characterization of Human Early Intervertebral
Disc Formation at Single-Cell Resolution. Advanced Science. 2023;25:e2206296. (*:Corresponding)
6. Sun J, Shin DY, Eiseman M, Yallowitz AR, Li N, Lalani S, Li Z, Cung M, Bok S, Debnath, S,
Marquez SJ, White TE, Khan A, Lorenz I, Shim JH, Lee FS, Xu R*, Greenblatt MB*. SLITRK5
is a novel negative regulator of hedgehog signaling in osteoblasts. Nature Communications.
2021;12:4611. (*: Corresponding)6

[Lecture Ⅲ]
Improved enamel acid resistance by
acidulated phosphate sodium monofluorophosphate solution
Ryouichi Satou, DDS, PhD
Senior Assistant Professor
Department of Epidemiology and Public Health, Tokyo Dental College
Abstract:
Sodium monofluorophosphate (MFP) is a component of fluoride-containing dentifrices and is morebiosafe than the conventional sodium fluoride (NaF). MFP can respond not only on the tooth surface
layer but also deep into the enamel. We aim to confirm that high concentrations of acid phosphate
MFP (AP-MFP, 9000 ppmF), used in professional care, could lead to a highly biosafe fluoride
application method that acts through the deep enamel layers. Sample groups were respectively treatedin vitro with NaF, acidulated phosphate fluoride (APF), MFP, and AP-MFP, and the samples werecompared against an untreated group. Characterizations after fluoride application confirmed that MFP
and AP-MFP treatments improved the acid resistance of enamel compared to that of conventional
methods. Furthermore, the acid resistance of highly concentrated MFPs improved by using phosphoricacid. Although the acid resistance from the AP-MFP method is not as good as that using APF, APMFP can act both on the surface layer and deep into the enamel. Moreover, AP-MFP retains fluoride
ions as much as APF does on the tooth surface. The proposed fluoride application method using APMFP introduces a dental treatment for acid resistance that is highly biosafe and penetrates deep layersof the enamel.

7

Curriculum Vitae
2012
DDS, Tokyo Dental College, Japan
2013-2014
Visiting researcher of Biomedical Research Division, National Institute of Advanced
Industrial Science and Technology (AIST), Japan
2014-2016
Research assistant, Oral Health Science Center of Tokyo Dental College, Japan2017
PhD, Epidemiology and Public Health, Tokyo Dental College, Japan2017-2020
Assistant Professor, Department of Epidemiology and Public Health, Tokyo Dental
College, Japan
2020-Present Senior Assistant Professor, Department of Epidemiology and Public Health, Tokyo
Dental College, Japan
Honors
2017
2018
2021
Award
2022

IADR/AADR/CADR “Salivary Research Group Award”
Tokyo Dental College Research Branding Project travel award
The 70th Annual Meeting of the Japanese Society for Oral Health, Excellent Presentation
Tokyo Dental College President's Encouragement Research Award

Research Fields of Interest
Preventive dentistry, Fluoride, De/Remineralization, Erosion, Toothpaste, Circadian rhythm, Clockgene
Selected Publications
1. Satou R, Sato M, Kimura M, Ishizuka Y, Tazaki M, Sugihara N, Shibukawa Y. Temporal
Expression Patterns of Clock Genes and Aquaporin 5/Anoctamin 1 in Rat Submandibular
Gland Cells. Frontiers in Physiology, 8. 320, 2017
2. Satou R, Yamagishi A, Takayanagi A, Higuchi T, Oyama T, Suzuki S, Sugihara N.
Relationship between Toothpaste Dilution Ratio and Droplets Generated during ToothBrushing. Int. J. Environ. Res. Public Health, 19(7), 4157, 2022
3. Satou R, Yamagishi A, Takayanagi A, Suzuki S, Dowen B, Sugihara NComparison ofinterproximal delivery and flow characteristics by dentifrice dilution and application of
prepared toothpaste delivery technique. PLoS One,17(10):e0276227, 2022
4. Satou R, Iwasaki M, Kamijo H, Sugihara N. Improved Enamel Acid Resistance using
Biocompatible Nano-hydroxyapatite Coating Method. Materials, 15(20), 7171, 2022
5. Satou R, Yamagishi A, Takayanagi A, Iwasaki M, Kamijo H, Sugihara N. Improved enamelacid resistance by highly concentrated acidulated phosphate sodium monofluorophosphate
solution. Materials, 15(20), 7298, 2022
6. Iwasaki M, Satou R*, Sugihara N. Development of root caries prevention by nanohydroxyapatite coating and improvement of dentin acid resistance. Materials, 15(22), 8263,
2022

8

[Lecture IV]
Cell-laden microspheres and oxygenation materials
applied in endodontic regeneration
Xie Li, PhD
Associated research fellow
State Key Laboratory of Oral Disease,West China College of Stomatology, Sichuan University
Abstract:
Stem cell-based dental pulp tissue regeneration has emerged as a promising alternative therapeuticstrategy for endodontic treatments. Cell-laden hydrogel microsphere system was demonstrated to be asuitable and effective vehicle for endodontic regeneration applications. Hydrogel microspheres
possess many advantages, such as large surface areas, ability to quickly transfer substances, 3D
extracellular matrix (ECM)-like structures, capable of acting as efficient carriers for both cell
expansion in vitro and cell transplantation in vivo. When inflammated or infected dental pulp tissues
are retrieved, a 6- to 9-mm-long root canal space is left empty and severe hypoxia within the root canal
space, characterized by a low oxygen content that may hinder the survival of the transplanted cells,
which may undergo instant death when the oxygen level drops to 1%. In situ generation of oxygen in
the anoxic regions by biomaterials that produce and deliver oxygen to the adjacent cells locally anddirectly is a distinctive approach to enhance cell survivability. Therefore, closely combined with thefrontier of regenerative medicine, we have constructed a series of new materials such as cell-ladenhydrogel microspheres, local-sustained oxygen generating materials, etc., and explored the applicationin dental pulp regeneration. For example, core-shell GelMA/Alginate hydrogel microspheres weredeveloped based on coaxial electrostatic droplet technology to facilitate the high-throughput
construction of pre-vascularization microtissues and facilitate the clinical transformation of stem cellbased dental pulp regeneration research. Sustained oxygen-generating biomaterials based on
CaO2/TiO2-x/PDMS were constructed for the regeneration of dental pulp, providing a new strategy to
improve the severe anoxic condition in the early stage after stem cell transplantation. Our work
demonstrated that core-shell GelMA/Alginate microspheres and CaO2/PDMS oxygen-generating
biomaterials have great application potential in endodontic regeneration field.

9Curriculum Vitae
2012/07-2012/12 R&D engineer, Chengdu Puchuan Biomaterials Corporation
2013/01-2015/01
Postdoctoral fellow, Sichuan University, West China College of Stomatology,
State Key Laboratory of Oral Disease
2015/04-2016/08
Assistant Research Fellow, Sichuan University, West China College of
Stomatology, State Key Laboratory of Oral Disease
2016/09-Present
Associate Research Fellow, Sichuan University, West China College of
Stomatology, State Key Laboratory of Oral Disease
Research Fields of Interest
1. Stem cell-laden hydrogel microspheres applied in dental pulp regeneration
2. Deep decontamination strategy for peri-implantitis management
3. Local-sustained oxygen-generating materials
Selected Publications
1. Xi Liang, Li Xie*, Qingyuan Zhang, Ge Wang, Siyuan Zhang, Mingyan Jiang, Ruitao Zhang,
Ting Yang, Xingyu Hu, Ziyang Yang, Weidong Tian**. GelMA-alginate core-shell
microcapsules as efficient delivery platform for prevascularized microtissues in endodontic
regeneration, Acta Biomaterialia, 144 (2022) 242–257.
2. Ting Yang, Li Xie*, Ruitao Zhang, Weidong Tian*, Microspheres and their potential inendodontic regeneration application, Chin J Dent Res 2022;25(1):29-36.
3. Qingyuan Zhang; Ting Yang; Ruitao Zhang; Xi Liang; Ge Wang; Yuan Tian; Li Xie*; Weidong
Tian*, Platelet lysate functionalized GelMA microspheres for improving angiogenesis in
endodontic regeneration. Acta Biomaterialia (2021)136, 441-455.
4. Ting Yang, Qingyuan Zhang, Li Xie*, Ruitao Zhang, Ruojing Qian, Yuan Tian, Guoqing Chen,
Weidong Tian*, hDPSC-laden GelMA microspheres fabricated using electrostatic microdroplet
method for endodontic regeneration, Materials Science and Engineering: C (2021) 121:111850.
5. Ruitao Zhang, Li Xie⁎, Hao Wu, Ting Yang, Qingyuan Zhang, Yuan Tian, Yuangang Liu, Xue
Han, Weihua Guo, Min He, Suru Liu, Weidong Tian**, Alginate/laponite hydrogel microspheres
co-encapsulating dental pulp stem cells and VEGF for endodontic regeneration, Acta
Biomaterialia (2020) 113:305–316.

10

[Keynote Lecture]
Pathophysiology of sleep bruxism in humans and challenges
for animal studies
Takafumi Kato, DDS, PhD
Professor
Department of Oral Physiology
Osaka University Graduate School of Dentistry
Sleep bruxism (SB) is characterized by frequent tooth grinding during sleep. Approximately 20% ofchildren and up to 10% of adults are affected by SB. SB is clinically significant since it is associatedwith damages to orodental tissues, prostheses, implants, and orofacial pain. However, the underlying
pathophysiological mechanisms of SB remain unknown. Sleep studies in humans have shown that
SB patients exhibit rhythmic masticatory muscle activity (RMMA) more frequently during sleep
than normal individuals. The occurrence of RMMA is under the influences of sleep homeostasis:
RMMA occurs in clusters particularly in light non-REM sleep during the ascending phase of sleep
cycles. These episodes are also associated with transient arousals and a sequence from transientautonomic and cortical activation to RMMA was found. However, SB patients otherwise healthy
exhibit a normal sleep architecture and similar level of masticatory muscle tone compared to normal
individuals. Therefore, motor system involved in generating RMMA, rather than sleep regulatory
system, would be more affected in SB patients. In animals, masticatory muscle contractions occur
during sleep, and the characteristics of the contractions differ between sleep states. Repetitive or
rhythmic contractions were found to occur during NREM sleep, in association with cortical andcardiac activations. Rhythmic masticatory muscle contractions can be induced by cortico-bulbar
stimulation during sleep less but responsiveness to stimulation is fluctuated by sleep and arousal
states. Thus, animal studies would provide additional insights into the pathophysiologicalmechanisms underlying SB. To further understand the pathophysiological mechanisms of SB, further
efforts are needed to integrate the findings from human and animal studies to clarify the factors
contributing to increased masticatory muscle activity during sleep.

11Curriculum Vitae
1994: Osaka University Faculty of Dentistry (DDS)
1998: Osaka University Graduate School of Dentistry (PhD)
1998-2001: Postdoctoral fellow/Research Assistant, Hôpital du Sacré-Cœur de Montréal, Universitéde Montréal Faculté de médecine dentaire and Centre recherche en science de neurologique,
Québec, Canada
2003: Associate Professor, Matsumoto Dental University, Shiojiri, Japan
2008: Chief, Matsumoto Dental University Hospital Dental Sleep Medicine Clinic
Associate Professor, Osaka University Graduate School of Dentistry, Department of Oral
Anatomy and Neurobiology, Suita, Japan
2009: President, IADR Neuroscience group
2016-current: Professor, Osaka University, Graduate School of Dentistry, Department of Oral
Physiology, Suita, Japan.
2022-current: Vice Dean, Osaka University, Graduate School of Dentistry
Adjunct: Osaka University Hospital Sleep Medicine Center, and Osaka University United Graduate
School of Child Development
Awards:1. Prix Jean-Paul Lussier (Ordre des dentists du Quebec, 2001)
2. Postdoctoral Research Award (CADR, 2001)
3. Distinguished Scientist Award/Young Investigator Award (IADR, 2005)
4. Yumikura Research Award (Osaka University School of Dentistry, 2014)
5. LION Award (Japanese Association for Oral Biology, 2022)

Selected Publications
1. Toyota R, Fukui KI, Kamimura M, Katagiri A, Sato H, Toyoda H, Rompré P, Ikebe K, Kato T.
Sleep stage-dependent changes in tonic masseter and cortical activities in young subjects withprimary sleep bruxism. Sleep. 2022;45(4):zsab207.
2. Shiraishi Y, Tachibana M, Shirota A, Mohri I, Taniike M, Yamashiro T, Kato T. Relationships
between cortical, cardiac, and arousal-motor activities in the genesis of rhythmic masticatory
muscle activity across sleep cycles in primary sleep bruxism children. Sleep.
2021;44(11):zsab156.
3. Kishi A, Haraki S, Toyota R, Shiraishi Y, Kamimura M, Taniike M, Yatani H, Kato T. Sleep
stage dynamics in young patients with sleep bruxism. Sleep. 2020;43(1):zsz202.
4. Yamada KI, Higashiyama M, Toyoda H, Masuda Y, Kogo M, Yoshida A, Kato T.
Experimentally induced rhythmic jaw muscle activities during non-rapid eye movement sleep infreely moving guinea pigs. J Sleep Res. 2019;28(5):e12823.
5. Kato T, Toyota R, Haraki S, Yano H, Higashiyama M, Ueno Y, Yano H, Sato F, Yatani H,
Yoshida A. Comparison of rhythmic masticatory muscle activity during non-rapid eye
movement sleep in guinea pigs and humans. J Sleep Res. 2018;27(4):e12608.

12

[Lecture Ⅴ]
The effect of cigarette smoke on interaction of host cells withperiodontal pathogen and periodontal healing
Kentaro Imamura, DDS, PhD
Senior assistant professor
Department of Periodontology, Tokyo Dental College
Oral Health Science Center, Tokyo Dental College
Abstract:
Cigarette smoking is a significant environmental risk factor for periodontal disease. Previous studies
have mainly focused on the effects of smoking on periodontal tissues, particularly in relation tonicotine. However, there is still limited understanding of the overall impact of cigarette smoke onhost cells, especially in the presence of periodontal pathogens. Our previous research revealed thatcigarette smoke condensate (CSC) exerts a concentration-dependent biphasic effect on the migrationof human gingival epithelial cells by altering the cytoskeleton and integrin expression. Additionally,
we reported that a significantly increased P. gingivalis invasion into epithelial cells when exposed to
low concentrations of CSC.
We further investigated the influence of CSC and P. gingivalis on the host cell signaling pathway,specifically mitogen-activated protein kinase (MAPK) pathway. Through the stimulation of the
MAPK, ERK1/2, and p38 signaling pathways, CSC influences cell migration. The activation of
ERK1/2 and p38 is suppressed by P. gingivalis infection, which reduces the CSC-induced migration
at least in part. However, other pathways are likely implicated in this modulatory process.
In recent years, there has been an increasing demand for new types of tobacco products. The market
share of heat-not-burn cigarettes (HNBCs) is 26% in Japan. HNBCs are characterized by lower
levels of nicotine and tar compared to conventional cigarettes. However, the effects of HNBC on
periodontal tissue and its healing remain largely unknown. Currently, we are actively investigating
the impact of HNBC on these aspects.

13Curriculum Vitae
2010
DDS, Tokyo Dental College, Tokyo, Japan2015

PhD, Graduate School of Dentistry, Tokyo Dental College, Tokyo, Japan

2015-2019

Assistant professor, Department of Periodontology, Tokyo Dental College, Tokyo,Japan

2016-2018

Visiting Scholar, Department of Prosthodontics, New York University College ofDentistry, New York, NY

2019-Present

Senior assistant professor, Department of Periodontology, Tokyo Dental College,
Tokyo, Japan

Selected Publications
1. Imamura K., Hamada Y., Yoshida W., Murakami T., Nakane-Koyachi S., Yoshikawa
K., Saito A. Investigating the effects of dehydrated human amnion-chorion membrane on
periodontal healing. Biomolecules 12: 857, 2022.
2. Imamura K, Suzuki E, Takeuchi T, Saito A. Clinical Outcomes of Periodontal Regenera
tive Therapy Using Recombinant Human Fibroblast Growth Factor-2 (FGF-2) with Modif
ied Minimally Invasive Surgical Technique for Intrabony Defects: A Case Series with 12-month Follow-up. Int J Periodontics Restorative Dent 42:507-513, 2022.
3. Imamura K., Tachi K., Takayama T., Shohara R., Kasai H., Dai J., and Yamano S. Re
leased fibroblast growth factor18 from a collagen membrane induces osteoblastic activity
involved with downregulation of miR-133a and miR-135a. J Biomater Appl 32:1382-139
1, 2018.
4. Imamura K., Kokubu E., Kita D., Ota K., Yoshikawa K., Ishihara K., and Saito A. Role of mitogen-activated protein kinase pathways in migration of gingival epithelial cells in
response to stimulation by cigarette smoke condensate and infection by Porphyromonas
gingivalis. J Periodontal Res 51:613-21, 2016.
5. Imamura K., Takayama S., Saito A., Inoue E., Nakayama Y., Ogata Y., Shirakawa S.,
Nagano T., Gomi K., Morozumi T., Akiishi K., Watanabe K., and Yoshie H. Evaluationof a novel immunochromatographic device for rapid and accurate clinical detection of Po
rphyromonas gingivalis in subgingival plaque. J Microbiol Methods 117:4-10, 2015.
6. Imamura K., Kokubu E., Kita D., Ota K., Ishihara K., and Saito A. Cigarette smoke condensate modulates migration of human gingival epithelial cells and their interactions w
ith Porphyromonas gingivalis. J Periodontal Res 50:411-21, 2015.

14

[Lecture Ⅵ]
POMC neuron targeting peptide regulates energy homeostasis
Ki Woo Kim, PhD
Professor
Division of Physiology, Department of Oral Biology, Yonsei University
College of Dentistry
Department of Applied Biological Science, BK21 FOUR, Yonsei
University College of Dentistry
The small humanin-like peptide (SHLP) is a mitochondrial-derived peptide (MDP) and known to be
implicated in diverse biological processes, including oxidative stress and senescence. However, its
functional roles in the regulation of energy homeostasis are not fully understood and its cognate
receptor is not identified. Here, we show that systemic or intracerebroventricular (ICV)
administrations of SHLP protected mice from high-fat diet (HFD)-induced obesity and improved
insulin sensitivity. In addition, SHLP suppressed food intake and promoted thermogenesis through theactivation of pro-opiomelanocortin (POMC) neurons of the arcuate nucleus of the hypothalamus(ARC). Furthermore, we, through a high-throughput structural complementation screening, identify
that chemokine receptor (CXCR) as a receptor for SHLP and it is required for POMC neuron activation.
Taken together, our study illustrates potential therapeutic actions of the SHLP on metabolic disorders
and provides mechanistic insights into its effects on energy homeostasis.

15

Curriculum Vitae
2004-20092009-20132013-20182018-2022
2023-Present

UT-Southwestern Medical Center, Dallas, TX
UT-Southwestern Medical Center, Dallas, TX
Yonsei University Wonju College of Medicine
Yonsei University College of Dentistry
Yonsei University College of Dentistry

PhD
Postdoctoral Fellow
Assistant Professor
Associate Professor
Professor

Research Field of Interest
Neuronal Control of Energy Metabolism and Alzheimer’s Disease
Energy Homeostasis and Psychological Disease
Selected Publications
1. Primary cilia regulate adaptive responses to fasting. Yang DJ, Tran LT, Yoon SG, Seong JK,
Shin DM, Choi YH, and Kim KW. Metab. Clin. Exp. 2022 Oct;135:155273. doi:
10.1016/j.metabol.2022.155273. Epub 2022 Aug 1
2.

Ventromedial Hypothalamic Primary Cilia Control Energy and Skeletal Homeostasis. Sun JS,
Yang DJ, Kinyua AW, Yoon SG, Seong JK, Kim J, Moon SJ, Shin DM, Choi YH, and Kim
KW. J Clin Invest. 2021 Jan 4;131(1):e138107. doi: 10.1172/JCI138107

3.

FoxO1 regulates leptin-induced mood behavior by targeting tyrosine hydroxylase Metabolism.
Son DH, Doan KV, Yang DJ, Sun JS, Kim SK, Kang N, Kang JY, Paik JH, DePinho RA, Choi
YH, Shin DM, Kim K.W. Metab. Clin. Exp. 2019 Feb;91:43-52.

4.

FoxO1 in Dopaminergic Neurons Regulates Energy Homeostasis and Targets Tyrosine
Hydroxylase. Doan KV, Kinyua AW, Yang DJ, Moh SH, Shong KE, Kim H, Park SK, Kim DH,
Kim I, Paik JH, Depinho RA, Yoon SG, Kim IY, Seong JK, Choi YH, and Kim K.W. Nat.
Commun. 2016 Sep 29;7:12733.2016.09.29

5.

FoxO1 in the ventromedial hypothalamus regulates energy balance. Kim K.W., Donato J.,
Berglund E.D., Choi Y.H., Kohno D., Elias C.F., DePinho R. A., Elmquist JK. J. Clin. Invest.
2012.July 122(7); 2578-89.

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