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LEUCINE-RICH AMELOGENIN PEPTIDE INDUCES OSTEOGENESIS
IN MOUSE EMBRYONIC STEM CELLS
by
Rungnapa Warotayanont
__________________________________________________________________________
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(CRANIOFACIAL BIOLOGY)
December 2008
Copyright 2008 RungnapaWarotayanont
Object Description
| Title | Leucine-rich amelogenin peptide induces osteogenesis in mouse embryonic stem cells |
| Author | Warotayanont, Rungnapa |
| Author email | warotaya@usc.edu; dorisan@gmail.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Cranio-Facial Biology |
| School | School of Dentistry |
| Date defended/completed | 2008-10-20 |
| Date submitted | 2008 |
| Restricted until | Unrestricted |
| Date published | 2008-11-18 |
| Advisor (committee chair) | Snead, Malcolm |
| Advisor (committee member) |
Paine, Michael Zhou, Yan Chai, Yang Frenkel, Baruch |
| Abstract | The extracellular matrix proteins in the developing enamel are constituted primarily by a group of highly conserved proteins called amelogenins. A number of amelogenin isoforms are expressed at distinctive stages during enamel development, but the function(s) for each isoform remain unclear. Emdogain, a mixture of porcine amelogenins has been used in clinical dentistry to promote cementogenesis and osteogenesis. A protein constituent in Emdogain called leucine-rich amelogenin peptide (LRAP) has been shown to possess a signaling property shown to induce osteogenic differentiation. However, the pathway(s) involved in the LRAP-mediated osteogenic effect is still unclear, and the function(s) exerted by LRAP to determine stem cell differentiation remains unknown. The purpose of the current study is to explore the effect of LRAP on osteogenesis in different cell types, including mouse embryonic stem (ES) cells and human bone marrow mesenchymal stem cells (hBMMSCs). In addition, the signaling pathway(s) responsible for the osteogenic effect of LRAP was examined. The LRAP-induced phenotype was determined using osteogenic-induced mouse ES cells, and by using osteogenic-induced hBMMSCs. The effect of LRAP on hBMMSCs in vivo was assessed by implantation of hBMMSCs, LRAP and hydroxyapatite/calcium phosphate carrier, into immunocompromised mice. To explore the molecular pathway(s) responsible for the inductive effects of LRAP, I measured beta-catenin and pSmad1/5/8 protein level in LRAP-treated ES cells by Western immunoblotting. The BMPSmad activity and Wnt promoter activity induced by LRAP was detected using a luciferase reporter containing BMP-Smad binding elements, or a reporter containing the TCF/LEF binding elements, respectively. The results suggest that ES cells, in response to endogenous an exogenous LRAP, showed an increase in bone marker gene expression, with increased calcium deposition in the mineralized matrix.; Human BMMSCs, after exposed to LRAP, showed enhanced osteoblastogenesis both in vitro and in vivo. On the other hand, adipogenesis was observed to be inhibited in LRAP-treated hBMMSCs primed for adipogenesis. The beta-catenin protein level and the Wnt-reporter activity was upregulated within 24 hours after LRAP treatment. The pSmad1/5/8 protein level and BMP-Smad-reporter activity was moderately increased at 4 days after LRAP treatment. These results suggest that the function of LRAP is to induce osteogenesis in stem cells via the activation of Wnt signaling pathway. |
| Keyword | LRAP; amelogenin; osteogenesis; Wnt signaling |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m1813 |
| Rights | Warotayanont, Rungnapa |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Warotayanont-2470 |
| Archival file | uscthesesreloadpub_Volume17/etd-Warotayanont-2470.pdf |
Description
| Title | Page 1 |
| Full text | LEUCINE-RICH AMELOGENIN PEPTIDE INDUCES OSTEOGENESIS IN MOUSE EMBRYONIC STEM CELLS by Rungnapa Warotayanont __________________________________________________________________________ A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (CRANIOFACIAL BIOLOGY) December 2008 Copyright 2008 RungnapaWarotayanont |
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