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.

本多样性行政补充申请 (PA-21-071) 是为了请求一年的 根据家长 RO1 补助金 (NIDCR, DE029709），标题为“牙周炎中骨再生的骨免疫学”。她将执行基本操作 研究阐明新型药物促进的致病性骨吸收的潜在机制 牙周炎病变中牙龈卟啉单胞菌产生的有毒脂质。与此同时，她将努力争取接受 在牙科计划中。 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研究 Kawai 实验室的研究得到了多样性管理补充文件 (PA-21-071) 的支持，该研究产生了两项共同成果： 撰写出版物并因其在 AADOCR（佐治亚州亚特兰大，3 月， 2022）。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） 递送至牙龈卟啉单胞菌外膜囊泡（OMV）中，可促进小鼠破骨细胞生成 破骨细胞前体 (RAW264.7) 与 OC-STAMP 和 DC-STAMP 表达上调相结合 在 RANKL 引发的 RAW264.7 细胞上。 PGD​​HC 在细菌细胞、OMV 以及宿主中的定位 破骨细胞很大程度上是未知的。尚不清楚 PGDHC 是否可以引发致病性促 OC 发生作用 对人类破骨细胞。 假设：我们假设牙龈卟啉单胞菌OMV中存在的PGDHC可以将PGDHC递送至破骨细胞 来自小鼠和人类的前体细胞，反过来又促进破骨细胞生成 OC-STAMP 和 DC-STAMP 表达的上调。 候选人的项目目标： 目标1：确定PGDHC在Pg细胞和OMV以及宿主细胞（小鼠 使用拉曼光谱仪（RAW264.7 细胞和人血单核细胞）。 目的2：研究牙龈卟啉单胞菌PGDHC对人破骨细胞生成的生理作用 上下文中，人源化小鼠将通过在上颌周围附着结扎线来诱导牙周炎 磨牙，然后口服接种 SPT-KO-Pg（PGDHC 缺陷）、gingipain-KO-Pg 和 WT-Pg。这 将评估牙周炎的病理表现。 完成这两个目标后，考生将掌握拉曼光谱和 牙周炎人源化小鼠模型，以及基本统计分析、数据解释和发布 一篇研究论文增强了她成为牙科学位课程候选人和未来的资格 牙科生物医学研究领域的临床医生/科学家。