Osteoimmunology of Retarded Bone Regeneration in Periodontitis

牙周炎骨再生迟缓的骨免疫学

• 批准号: 10667111
• 负责人: TOSHIHISA KAWAI
• 金额: $ 7.55万
• 依托单位: NOVA SOUTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10667111
• 关键词: Administrative Supplement; Award; Basic Science; Biomedical Research; Bone Regeneration; Bone Resorption; Cells; Data Analyses; Degree program; Dental; Dentistry; Future; Genotype; Graduate Degree; Grant; Hematopoietic stem cells; Hispanic; Human; Lesion; Ligature; Lipids; Maintenance; Maxilla; Membrane; Methods; Mus; National Institute of Dental and Craniofacial Research; Oral; Osteoclasts; Paper; Parents; Pathogenicity; Pathologic; Periodontitis; Physiological; Porphyromonas gingivalis; Publications; Publishing; Raman Spectrum Analysis; Research; Research Project Grants; Scientist; Statistical Data Interpretation; TNFSF11 gene; Travel; Up-Regulation; Vesicle; Virulent; dihydroceramide; gingipain; humanized mouse; monocyte; mouse model; novel; osteoclastogenesis; osteoimmunology; periodontopathogen; programs; spectroscope

This application for Diversity Administrative Supplement (PA-21-071) is written to request for the one-year support for Hispanic Post Bachelorette Trainee, Ms. Elizabeth Leon, under the parent RO1 grant (NIDCR, DE029709), titled, “Osteoimmunology of regarded bone regeneration in periodontitis.” She will perform the basic research to elucidate the mechanism underlying the pathogenic bone resorption which is promoted by the novel virulent lipid produced by P, gingivalis in periodontitis lesion. Parallelly, she will be working toward acceptance in the program of dentistry. Candidate’s research project background: In the past year, the candidate performed the basic biomedical research in Kawai lab supported by Diversity Administrative Supplement (PA-21-071) which resulted in two co- authored publications and receiving of Bloc travel award for her presentation in AADOCR (Atlanta, GA, March, 2022). She discovered that P. gingivalis’ unique lipid, phosphoglycerol dihydroceramide (PGDHC), as it was delivered in P. gingivalis’ outer membrane vesicle (OMV), can promote the osteoclastogenesis from mouse osteoclast precursors (RAW264.7) in conjunction with upregulation of OC-STAMP and DC-STAMP expressions on the RANKL-primed RAW264.7 cells. The localization of PGDHC in the bacterial cell, OMVs as well as host osteoclasts is largely unknown. It is also not known whether PGDHC can elicit pathogenic pro-OC-genesis effect on human osteoclasts. Hypothesis: We hypothesized that PGDHC present in OMV of P. gingivalis can deliver the PGDHC to osteoclast precursors derived from mice as well as human which, in turn, promotes osteoclastogenesis in conjunction with the upregulation of OC-STAMP and DC-STAMP expressions. Project Objectives for Candidate: Objective 1: To determine the localization of PGDHC in Pg cell and OMV as well as host cells (mouse RAW264.7 cells and human blood monocytes) using a Raman Spectroscope. Objective 2: To study the effect of P. gingivalis’ PGDHC on the human osteoclastogenesis in the physiological context, the humanized mice will be induced of periodontitis by attachment of ligature around the maxillary molar, followed by the oral inoculation with SPT-KO-Pg (PGDHC deficient), gingipain-KO-Pg and WT-Pg. The pathologic manifestation of periodontitis will be evaluated. After completing these two objectives, the candidate will have mastered the methods of Raman spectroscopy and humanized mouse model of periodontitis, as well as basic statistical analysis, interpretation of data and publishing a research paper which strengthen her credential to be a candidate for dental degree program and future clinician/scientist in the field of dental biomedical research.

多样性行政补充申请（PA-21-071）是书面申请一年 支持西班牙裔后单身女学员，伊丽莎白莱昂女士，根据父母的RO 1赠款（NIDCR， DE 029709），标题为“牙周炎中骨再生的骨免疫学”。她将表演基本的 研究阐明了新的促进致病性骨吸收的机制， 牙龈卟啉单胞菌在牙周炎病变中产生的毒性脂质。但她会努力接受 在牙科项目中。 候选人的研究项目背景：在过去的一年里，候选人进行了基础生物医学 Kawai实验室的研究得到了多样性行政补充（PA-21-071）的支持，这导致了两个共同的， 撰写出版物，并因在AADOCR（亚特兰大，佐治亚州，3月， 2022年）。她发现牙龈卟啉单胞菌独特的脂质，磷酸甘油二氢神经酰胺（PGDHC）， 在牙龈卟啉单胞菌的外膜囊泡（OMV）中释放，可以促进小鼠破骨细胞的生成， 破骨细胞前体（RAW264.7）与OC-STAMP和DC-STAMP表达的上调结合 在RANKL-致敏的RAW 264.7细胞上。PGDHC在细菌细胞、OMV和宿主中的定位 破骨细胞在很大程度上是未知的。PGDHC是否能引起致病性促OC生成作用也不清楚 对人类破骨细胞的影响 假设：我们假设存在于牙龈卟啉单胞菌OMV中的PGDHC可以将PGDHC传递给破骨细胞 来源于小鼠和人的前体，其反过来促进破骨细胞生成， OC-STAMP和DC-STAMP表达上调。 候选人的项目目标： 目的1：确定PGDHC在Pg细胞、OMV及宿主细胞（小鼠）中的定位 RAW264.7细胞和人血单核细胞）。 目的2：研究牙龈卟啉单胞菌PGDHC对人破骨细胞生理性分化的影响 在上下文中，人源化小鼠将通过在上颌骨周围附着结扎线来诱导牙周炎。 磨牙，随后口服接种SPT-KO-Pg（PGDHC缺陷型）、牙龈卟啉酶-KO-Pg和WT-Pg。 将评估牙周炎的病理表现。 在完成这两个目标后，候选人将掌握拉曼光谱和 牙周炎的人源化小鼠模型，以及基本的统计分析、数据解释和出版 一份研究论文，加强了她作为牙科学位课程候选人的资格， 牙科生物医学研究领域的临床医生/科学家。