Osteoimmunology of Retarded Bone Regeneration in Periodontitis

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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.