Mar–Apr 2021RESEARCH BULLETIN

PERIO RESEARCH COLLABORATION

PERIODONTAL DISEASE PREDICTS MAJOR ADVERSE CARDIOVASCULAR EVENTS

A group of Forsyth Institute and Harvard School of Dental Medicine scientists have found that people with periodontitis are at higher risk of suffering major cardiovascular events,

according to recently published papers in the Journal of Periodontology and the Journal of American College of Cardiology Imaging. Drs. Thomas Van Dyke and Karim El Kholy, from the Forsyth Institute and our Department of Oral Medicine, Infection and Immunity, collaborated with Dr. Ahmed Tawakol and colleagues, from the Cardiology Division of Massachusetts General Hospital in a longitudinal study that demonstrated that oral inflammation associated with active gum disease was predictive of arterial inflammation, which can cause heart attacks, strokes, and other dangerous manifestations of cardiovascular disease.

The research team used positron emission tomography and computer tomography (PET and CT) scans on 304 individuals to visualize and quantify inflammation in the arteries and gums of each patient. In follow-up studies approximately

four years later, 13 of those individuals developed major adverse cardiovascular events. Periodontal inflammation was found to be predictive of major adverse cardiovascular events, even after the investigators controlled for other risk factors, such as smoking, high blood pressure, obesity, and diabetes. Furthermore, researchers found that a history of periodontal disease was not associated with an increased risk in cardiovascular events. Patients who did not have actively inflamed gums had a lower risk of cardiovascular disease—even if those individuals had a prior history of periodontal disease as evidenced by periodontal bone loss on their reconstructed CT scans. The hypothesized mechanism linking periodontal inflammation and cardiovascular disease was published in the Journal of American College of Cardiology Imaging. Local periodontal inflammation activates and mobilizes cells signaling through bone marrow, which triggers the inflammation of arteries, leading to major adverse cardiovascular events.

The results are substantial and suggest that patients who are at risk of cardiovascular disease, or currently suffering from cardiovascular disease, should be regularly screened and treated if necessary for periodontal disease to decrease their risk of developing threatening cardiovascular events.

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FACULTY FEATURE

ROSALYN SULYANTO

Congratulations to Dr. Rosalyn Sulyanto who was recently promoted to assistant professor of Developmental Biology and Associate, Department of Dentistry, Boston Children’s Hospital.

Dr. Sulyanto graduated with a double major in bioengineering and materials science and engineering from University of California, Berkeley and received her DMD degree with research honors from Harvard School of Dental Medicine in 2011. While at Harvard, she conducted research on osteoclast development as a Howard Hughes Medical Institute Fellow.

She then completed her residency in pediatric dentistry at Nationwide Children’s Hospital/The Ohio State University and was awarded a masters degree. In 2014, Dr. Sulyanto joined the faculty at Boston’s Children’s Hospital (BCH) and the Department of Developmental Biology at HSDM, and became the director of

post-doctoral research at BCH in 2017. Since joining the faculty, Dr. Sulyanto has mentored/co-mentored more than 20 pediatric dental residents and dental students, several of whom have earned national recognition for their research accomplishments.

Her research interests include the prevention of early childhood caries and the oral microbiome. Among other publications, her research on sealants on primary molars

was featured as the cover of the August 2019 Journal of the American Dental Association issue. Her research on the dominant structure of the infant oral microbiome and how it establishes early, suggesting that it persists throughout life, was published in the July 2019 Scientific Reports.

Currently, Dr. Sulyanto is conducting translational research to elucidate the microbial and microstructural mechanisms of action of silver diamine fluoride as well as microbiota associated with odontogenic infections. Her research mentors include Dr. Man Wai Ng, dentist-in-chief, department of dentistry at Boston’s Children’s Hospital, associate professor of Developmental Biology at HSDM; Dr. Ann Griffen, professor of pediatric dentistry at The Ohio State University, and Dr. Sunita Ho, professor of preventive and restorative dental sciences at the University of California, San Francisco.

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Bavarian R, Khawaja S, Treister N. Oral appliances in the management of neuropathic orofacial pain: A retrospective case series. Oral Diseases 2021; Mar 1.

Chung M, Zhao N, Meier R, Koestler D, Wu G, de Castillo E, Paster B, Charpentier K, Izard J, Kelsey K, Michaud D. Comparisons of oral, intestinal, and pancreatic bacterial microbiomes in patients with pancreatic cancer and other gastrointestinal diseases. Journal of Oral and Microbiology 2021;13(1):1887680.

Cross K, Dewhirst F, Podar M. Complete genome sequence of human oral Actinomyces sp. HMT897 strain ORNL0104, a host of the Saccharibacterium (TM7) HMT351. Microbiology Resource Announcements 2021;10(14):e00040-21.

Da Silva J, Ni S, Lee C, Elani H, Ho K, Thomas C, Kuwajima Y, Ishida Y, Kobayashi T, Ishikawa-Nagai S. Association between cognitive health and masticatory conditions: a descriptive study of the national database of the universal healthcare system in Japan. Aging 2021; Mar 19;13.

Gharpure A, Latimer J, Aljofi F, Daubert D. Role of thin gingival phenotype and inadequate keratinized mucosa width (< 2 mm) as risk indicators for peri-implantitis and peri-implant mucositis. Journal of Periodontology 2021; Apr 15.

Hua Z, Ouellette M, Makkay A, Papke R, Zhaxybayeva O. Nutrient supplementation experiments with saltern microbial communities implicate utilization of DNA as a source of phosphorus. ISME Journal 2021; Apr 12.

Juel Mortensen L, Lorenzen M, Jørgensen A, Albrethsen J, Jørgensen N, Møller S, Andersson A, Juul A, Blomberg Jensen M. Possible relevance of soluble luteinizing hormone receptor during development and adulthood in boys and men. Cancers (Basel) 2021;13(6):1329.

Keibler M, Dong W, Korthauer K, Hosios A, Moon S, Sullivan L, Liu N, Abbott K, Arevalo O, Ho K, Lee J, Phanse A, Kelleher J, Iliopoulos O, Coloff J, Vander Heiden M, Stephanopoulos G. Differential substrate use in EGF- and oncogenic KRAS-stimulated human mammary epithelial cells. FEBS Journal 2021; Apr 3.

Kota S, Lim Z, Kota S. Elavl1 Impacts osteogenic differentiation and mRNA levels of genes involved in ECM organization. Frontiers in Cell and Developmental Biology 2021;9:606971.

Latimer J, Gharpure A, Kahng H, Aljofi F, Daubert D. Interproximal open contacts between implant restorations and adjacent natural teeth as a risk-indicator for peri-implant disease – A cross sectional study. Clinical and Oral Implants Research 2021; Feb 25.

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PUBLICATIONSDEVELOPMENTAL BIOLOGYChoi S, Liu J, Mari S, Garber I. Content analysis of living historical memory around the world: Terrorization of the anglosphere, and national foundations of hope in developing societies. Memory Studies 2021; Feb 25.

Giddon D, Roth M, Garber I. Relationship of perceived facial asymmetry to attributed personality traits. Psychology and Psychophysiology 2021;14(1): 5–13.

Kantaputra P, Dejkhamron P, Intachai W, Ngamphiw C, Ketudat Cairns J, Kawasaki K, Ohazama A, Olsen B, Tongsima S, Angkurawaranon S. A novel P3H1 mutation is associated with osteogenesis imperfecta type VIII and dental anomalies. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology 2021;28:4564.

Keibler M, Dong W, Korthauer K, Hosios A, Moon S, Sullivan L, Liu N, Abbott K, Arevalo O, Ho K, Lee J, Phanse A, Kelleher J, Iliopoulos O, Coloff J, Vander Heiden M, Stephanopoulos G. Differential substrate use in EGF- and oncogenic KRAS-stimulated human mammary epithelial cells. FEBS Journal 2021; Apr 3.

Liu D, Alhazmi N, Matthews H, Lee M, Li J, Hecht J, Wehby G, Moreno L, Heike C, Roosenboom J, Feingold E, Marazita M, Claes P, Liao E, Weinberg S, Shaffer J. Impact of low-frequency coding variants on human facial shape. Science Reports 2021;11(1):748.

Teichmann D, Hallmann A, Wolfart S, Teichmann M. Identification of dental pain sensation based on cardiorespiratory signals. Biomedical Engineering 2021;66(2):159-165.

Ustriyana P, Schulte F, Gombedza F, Gil-Bona A, Paruchuri S, Bidlack F, Hardt M, Landis W, Sahai N. Spatial survey of non-collagenous proteins in mineralizing and non-mineralizing vertebrate tissues ex vivo. Bone Reports 2021;14:100754.

Welty F, Schulte F, Alfaddagh A, Elajami T, Bistrian B, Hardt M. Regression of human coronary artery plaque is associated with a high ratio of (18-hydroxy-eicosapentaenoic acid + resolvin E1) to Leukotriene B. FASEB Journal 2021;35(4):e21448.

ORAL MEDICINE, INFECTION AND IMMUNITY

Aldawood Z, Moyer D, Woo SB. A bronchogenic cyst masquerading as a tongue mass. Head and Neck Pathology 2021; Feb 27.

Alhazmi N, Carroll S, Kawasaki K, Woronowicz K, Hallett S, Macias Trevino C, Li E, Baron R, Gori F, Yelick P, Harris M, Liao E. Synergistic roles of Wnt modulators R-spondin2 and R-spondin3 in craniofacial morphogenesis and dental development. Science Reports 2021;11(1):5871.

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Mawardi H, Treister N, Felemban O, Alamoudi W, Algohary G, Alsultan A, Alshehri N, Tazi I, Shaheen M, Alsharani M, Alshemmari S, Arat M, Bekadja M, Al-Khabori M, Okaily S, Ali N, Abujazar H, Jastaniah W, Hamidieh A, Hashmi S, Aljurf M. Current practice of oral care for hematopoietic stem cell transplant patients: A survey of the eastern Mediterranean blood and marrow transplantation group. Hematology and Oncology Stem Cell Therapies 2021; Feb 11.

Niu W, Lim T, Alshihri A, Rajappa R, Wang L, Kurisawa M, Spector M. Platelet-derived growth factor stimulated migration of bone marrow mesenchymal stem cells into an injectable gelatin-hydroxyphenyl propionic acid matrix. Biomedicine 2021; Feb 17;9(2).

Oner F, Alvarez C, Yaghmoor W, Stephens D, Hasturk H, Firatli E, Kantarci A. Resolvin E1 regulates Th17 function and T cell activation. Frontiers in Immunology 2021 Mar 17;12:637983.

Sandhu S, Sankar V. Osteonecrosis of the jaw secondary to haematopoietic stem cell transplantation. BMJ Case Reports 2021;4;14(3).

Si Y, Song J, Fang Z, Han X, Jiang S. MicroRNA-146a regulates the production of cytokines in lymphocytes stimulated by Porphyromonas gingivalis lipopolysaccharide. West China Journal of Stomatology 2021;39(1):26-31.

Yarom N, Hovan A, Bossi P, Ariyawardana A, Jensen S, Gobbo M, Saca-Hazboun H, Kandwal A, Majorana A, Ottaviani G, Pentenero M, Nasr N, Rouleau T, Lucas A, Treister N, Zur E, Ranna V, Vaddi A, Cheng K, Barasch A, Lalla R, Elad S. Correction to: Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and Clinical Practice Guidelines - Part 1: Vitamins, minerals and nutritional supplements. Supportive Care in Cancer 2021; Mar 24.

RESTORATIVE DENTISTRY AND BIOMATERIALS SCIENCESLiao W, Tsai Y, Chen K, Blicher B, Chang S, Yeung S, Chang M, Jeng J. Cracked teeth: Distribution and survival at 6 months, 1 year and 2 years after treatment. Journal of the Formosan Medical Association 2021: S0929-6646(21)00125.

Michot B, Casey S, Gibbs J. Effects of CGRP-primed dental pulp stem cells on trigeminal sensory neurons. Journal of Dental Research 2021; Apr 10.

Park S. Ten-year follow-up of patient-centered comprehensive care using case completion curriculum. Journal of Dental Education 2021; Apr 1.

Wittneben J, Igarashi K, Brägger U, Daniel B, Schimmel M, Wismeijer D. Vertical eruption of anterior maxillary teeth adjacent to single-implant-supported crowns: An assessment after a 3-year follow-up period. Journal of Prosthetic Dentistry 2021; Mar 4.

Van Doren E, Breitman L, Lee J, Chutinan S, Ohyama H. Piloting an online, dental education platform to supplement students’ operative learning. Journal of Dental Education 2021; Mar 25.

ORAL HEALTH POLICY AND EPIDEMIOLOGY Agaku I, Egbe C, Ayo-Yusuf O. Circumvention of COVID-19-related restrictions on tobacco sales by the e-cigarette industry in South Africa and comparative analyses of e-cigarette vs cigarette volume sales during 2018-2020. Preventive Medicine 2021; Mar 18:106526.

Amen T, Kim I, Peters G, Gutiérrez-Sacristán A, Palmer N, Simon L. Emergency department visits for dental problems among adults with private dental insurance: A national observational study. American Journal of Emergency Medicine 2021; 44:166-170.

Riordain R, Glick M, Mashhadani S, Aravamudhan K, Barrow J, Cole D, Crall J, Gallagher J, Gibson J, Hegde S, Kaberry R, Kalenderian E, Karki A, Celeste R, Listl S, Myers S, Niederman R, Severin T, Smith M, Murray Thomson W, Tsakos G, Vujicic M, Watt R, Whittaker S, Williams D. Developing a standard set of patient-centred outcomes for adult oral health - An international, cross-disciplinary consensus. International Dental Journal 2021;71(1):40-52.

Thompson L, Chen H. Physiology of aging of older adults: Systemic and oral health considerations – 2021 Update. Dental Clinics of North America 2021;65(2):275-284.

ORAL AND MAXILLOFACIAL SURGERYApon I, Rogers-Vizena C, Koudstaal M, Allori A, Peterson P, Versnel S, Ramirez J. Barriers and facilitators to the international Implementation of standardized outcome measures in clinical cleft practice. Cleft Palate Craniofacial Journal 2021; Mar 5.

Askar H, Aronovich S, Christensen B, McCain J, Hakim M. Is arthroscopic disk repositioning equally efficacious to open disk repositioning? A systematic review. Journal of Oral and Maxillofacial Surgery 2021; Feb 15.

Beck N, Nuzzi L, Parry G, Padwa B. Assessing knowledge and promoting awareness of chronic recurrent multifocal osteomyelitis among oral and maxillofacial surgeons. Journal of Oral and Maxillofacial Surgery 2021; Jan 28.

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Beaumont C, Dunaway D, Padwa B, Forrest C, Koudstaal M, Caron C. Extracraniofacial anomalies in Treacher Collins syndrome: A multicentre study of 248 patients. International Journal of Oral and Maxillofacial Surgery 2021; Mar 19.

Ganske I, Sanchez K, Le E, Langa O, Sharif-Askary B, Ross E, Santiago P, Meara J, Padwa B, Allori A. Time-driven, activity-based costing of presurgical infant orthopedics: A critical component of establishing value of Latham appliance and nasoalveolar molding. Plastic and Reconstructive Surgery 2021;147(3):444-54.

Harris J, Caprio R, Resnick C. Do infants with Robin Sequence have improved feeding and weight gain after mandibular distraction? Journal of Oral and Maxillofacial Surgery 2021; Jan 28.

Huang L, Yin X, Chen J, Liu R, Xiao X, Hu Z, He Y, Zou S. Lithium chloride promotes osteogenesis and suppresses apoptosis during orthodontic tooth movement in osteoporotic model via regulating autophagy. Bioactive Materials 2021;6(10):3074-84.

Ji Y, Harris J, Gibson L, McKinley S, Phitayakorn R.The efficacy of Liposomal Bupivacaine for opioid and pain reduction: A systematic review of randomized clinical trials. Journal of Surgical Research 2021;264:510-533.

Lee C, Xhori O, Tannyhill R, Kaban L, Peacock Z. Variables associated with stability after Le Fort I osteotomy for skeletal class III malocclusion. International Journal of Oral and Maxillofacial Surgery 2021; Feb 28.

Liapaki A, Thamm J, Ha S, Monteiro J, McCain J, Troulis M, Guastaldi F. Is there a difference in treatment effect of different intra-articular drugs for temporomandibular joint osteoarthritis? A systematic review of randomized controlled trials. International Journal of Oral and Maxillofacial Surgery 2021; Feb 25.

Niu Z, Zhang K, Yao W, Li Y, Jiang W, Zhang Q, Troulis M, August M, Chen Y, Han Y. A meta-analysis and systematic review of the incidences of complications following facial thread-lifting. Aesthetic Plastic Surgery 2021; Apr 5.

Posnick J, Kaban L. A conceptual framework for treating jaw deformities in patients with abnormal condyles: Preservation versus replacement of the glenoid fossa-disc-condyle-ramus. International Journal of Oral and Maxillofacial Surgery 2021; Apr 10.

Raborn L, Burke A, Ebb D, Collins M, Kaban L, Boyce A. Denosumab for craniofacial fibrous dysplasia: Duration of efficacy and post-treatment effects. Osteoporosis International 2021; Mar 27.

Rooijers W, Renkema R, Loudon S, Khoshnaw T, Padwa B, Dunaway D, Koudstaal M, Forrest C, Caron C. Ocular and adnexal anomalies in craniofacial microsomia: Type and prevalence in a multicentre cohort study. International Journal of Oral and Maxillofacial Surgery 2021:S0901-5027(21)00095-3.

MULTI DEPARTMENTAL

Okuji D, Lin J. Predicting negative outcomes while awaiting dental treatment under general anesthesia.Journal of Dentistry for Children 2021:15;88(1):3-10.

Wu X, Park S, Friedland B. A survey of workforce issues faced by New England dental community health centers. Journal of the Massachusetts Dental Society 2021; 69(4):18-22.

Francesca Gori Receives Burton C. Borgelt/SCADA Faculty Award

Congratulations to Dr. Francesca Gori, assistant professor of Oral Medicine, Infection and Immunity, program director for the Harvard Forsyth Research Academy, and director of predoctoral research at HSDM. Dr. Gori was chosen by the Board

of Directors of the Student Competition for Advancing Dental Research and its Application (SCADA) as the 2021 Burton C. Borgelt/SCADA Faculty Advisory Award recipient. This award honors a faculty advisor who has distinguished herself as a dental scientist and has had a significant impact on the lives of dental students as a research mentor. Dean Giannobile noted, “Dr. Francesca Gori is an instrumental and inspiring member of the faculty, contributing significantly to both the Advanced Graduate Education, and DMD students’ education in both basic science research and didactic instruction.”

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HSDM SCIENCE SPEAKER SERIESZoom links will be announced a week prior to the 12 – 1 pm talks.

2021-22 Osteology Foundation Fellow

Young Woo Song, DDS, PhD, clinical and research assistant professor, Department of Periodontology at Yonsei University College of Dentistry in South Korea, joined HSDM this past March. Dr. Song is currently a Research Fellow

in the Nagai/Kim/Da Silva Lab in the Department of Oral Medicine, Infection and Immunity through February 2022.

Dr. Song, an Osteology Foundation Fellowship recipient, plans to work on a broad spectrum of research projects in the field of oral and maxillofacial regeneration including in vitro, in vivo, and clinical studies. Specifically, he will be working on: 1) Establishing biomimetic interface of peri-implant soft tissues; Basal lamina-mediated epithelial attachment and perpendicular ligamentous barrier at the epithelial junction; 2) A novel paradigm for blood brain barrier-independent molecular passage to the brain: Retrograde axonal transit of craniofacial tissue exosome; and, 3) Pathological and physiological roles of a novel alternative splicing variant of receptor activator of NF-kappa B, soluble RANK (sRANK), in bone, CNS and immune systems.

Dr. Song’s recent work includes: 1) Bone augmentation using small molecules with biodegradable calcium sulfate particles in a vertical onlay graft model; 2) Locally applied slow-release of minocycline microspheres in the treatment of peri-implant mucositis; 3) Bone morphogenetic protein-2 solution in damaged extraction sockets; and, 4) Clinical benefits of ridge preservation for implant placement compared to natural healing in maxillary teeth.

"I am deeply interested in newly- developed materials related to periodontal and peri-implant tissue regeneration. It is my great honor and pleasure to have an opportunity to work with the research team of Drs. David Kim, Shigemi Nagai, and John Da Silva at HSDM.”

MAY 13, 2021 Yi-Xian Qin PhDProfessor and Chair of Biomedical Engineering, Stony Brook University“Bone Adaptation via Dynamic Loading and Piezo1 Mechanotransduction”

JUNE 10, 2021 Michael Longaker, MD, MBAProfessor and Vice Chair of Plastic and Reconstructive Surgery, Co-Director, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University

SEPTEMBER 9, 2021 Benjamin Wu, DDS, PhDProfessor and Chair of the Division of Advanced Prosthodontics, Director of the Weintraub Center for Reconstructive Biotechnology, University of California, Los Angeles

OCTOBER 7, 2021 Lynda F. Bonewald, PhDDistinguished University Professor, Anatomy, Cell Biology, Physiology and Orthopaedic Surgery, Indiana University

NOVEMBER 18, 2021Tamara Alliston, PhDProfessor of Orthopaedic Surgery, Department of Medicine, University of California, San Francisco

DECEMBER 9, 2021Jean X. Jiang, PhDProfessor and Zachary Distinguished University Chair, Department of Biochemistry and Structural Biology, University of Texas at San Antonio

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A PUBLICATION OF THE OFFICE OF RESEARCH

Yingzi Yang, PhD Professor of Developmental Biology andAssociate Dean for Research Dawn M. DeCosta Editor, Design, and Layout

Heather M. Denny Editing

Lia Sgourakes Editing Ashley SimmonsEditing

If you have questions, or comments, please contact Dawn M. DeCosta, Director of Research Operations at 617-824-0715 (or) dawn_decosta@hsdm.harvard.edu.

The Editorial Board of the Journal of Endodontics recently announced the winners of the 2021 JOE Awards. The JOE Publication Awards are presented to authors of published papers in the Journal of Endodontics that represent innovative thought and significant advances in the endodontic field.

The purpose of the study, “Immunomodulation Mediated by Azithromycin in Experimental Periapical Inflammation” was to compare the immunomodulatory effect of azithromycin (AZM), ampicillin (AMP), amoxicillin, and clindamycin in vitro and AZM on preexisting periapical lesions compared with AMP. The study showed that AZM led to the resolution of preexisting experimental periapical inflammation. Data provided a perspective on host response in antibiotic selection for endodontic treatment. However, well-designed clinical trials are necessary to better elucidate the benefits of AZM as an adjunctive therapy for endodontic treatment when antibiotic therapy is recommended. Although both AZM and AMP were effective on preexisting periapical lesions, AZM led to advanced wound healing, probably depending on its immunomodulatory effect.

Collaborative Project Led by Dr. Ana AndradaReceives 2021 Journal of Endodontics’ Award

The Basic Research Award went to Drs. Ana Cristina Andrada (Detroit Mercy Dental), Mariane Maffei Azuma (Michigan), Hisako Furusho (Hiroshima University), Kimito Hirai (Michigan), Shuang Xu (Forsyth), Robert White (HSDM), and Hajime Sasaki (Michigan) for their project, “Immunomodulation Mediated by Azithromycin in Experimental Periapical Inflammation.” This work was Dr. Andrada’s DMSc thesis project while at HSDM.