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.

本多样性行政补助金申请书(PA-21-071)是为申请为期一年而编写的 支持西班牙裔后单身女实习生伊丽莎白·利昂女士，根据父母RO1赠款(NIDCR， DE029709)，标题为“牙周炎中被视为骨再生的骨免疫学”。她将表演基本的 研究阐明该小说促进病理性骨吸收的机制 牙周炎病变中牙龈假单胞菌产生的致死性脂质。与此同时，她将努力争取被接受 在牙科的课程中。 应聘者研究项目背景：在过去的一年里，应聘者进行了基础生物医学 由多样性行政补充(PA-21-071)支持的河口实验室研究，导致两个共同 她在AADOCR(佐治亚州亚特兰大，3月， 2022年)。她发现，牙龈假单胞菌独特的脂质--磷酸甘油二氢神经酰胺(PGDHC) 牙龈假单胞菌外膜囊泡(OMV)能促进小鼠破骨细胞的形成 破骨细胞前体(RAW264.7)与OC-STAMP和DC-STAMP表达上调 在RANKL诱导的RAW264.7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。也不知道PGDHC是否可以引起致病的促OC作用 在人类破骨细胞上。 假设：我们推测牙龈假单胞菌OMV中存在的PGDHC可以将PGDHC传递给破骨细胞。 来自小鼠和人类的前体细胞，反过来又促进破骨细胞的形成 OC-STAMP和DC-STAMP表达式的上调。 应聘者的项目目标： 目的：研究PGDHC在PG细胞、OMV和宿主细胞(小鼠)中的定位 RAW264.7细胞和人血单核细胞)。 目的：从生理学角度研究牙龈假单胞菌PGDHC对人破骨细胞生成的影响。 背景：人源化小鼠将通过上颌骨周围结扎的方法诱导牙周炎 然后分别口服SPT-KO-PG(PGDHC缺陷型)、牙周炎-KO-PG和WT-PG。这个 将对牙周炎的病理表现进行评估。 在完成这两个目标后，应聘者将掌握拉曼光谱和 人性化的牙周炎小鼠模型，以及基本的统计分析、数据解释和发布 一篇研究论文，加强了她作为牙科学位课程候选人和未来的资质 牙科生物医学研究领域的临床医生/科学家。