Date of Completion

12-11-2013

Embargo Period

12-11-2013

Keywords

Osterix, Skeletal Progenitor, Stromal Cell, Mesenchymal, Reporter Mouse, BAC Transgenesis

Major Advisor

Dr. Peter F. Maye

Associate Advisor

Dr. John Harrison

Associate Advisor

Dr. William Upholt

Associate Advisor

Dr. Barbara Kream

Field of Study

Biomedical Science

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Multipotent skeletal progenitor cells that reside in the bone marrow and contribute to the maintenance and repair of bone tissue are difficult to identify and, as a result, remain poorly understood. Osterix is a zinc finger transcription factor, which functions as a key regulator of bone formation. Cells of the osteoblast lineage generate bone tissue by depositing a mineralized matrix [1, 2]. Osterix is selectively expressed in cells of the osteoblast lineage and has an essential function in osteoblast commitment and bone formation [1, 3]. While it is generally accepted that Osterix is expressed in early osteogenic precursors [3, 5-7], recent studies from our lab and others have suggested that Osterix may be expressed at an even earlier stage of the lineage, being present in a multipotent bone marrow skeletal progenitor cell population, which can be expanded in vitro as a bone marrow mesenchymal stem cells (BMSCs).

To further explore the expression of Osterix in early bone marrow skeletal progenitor cells, we have generated Osterix-Cherry reporter mice. Preliminary characterization of this animal model suggests reporter expression accurately represents endogenous Osterix expression, being largely restricted to skeletal tissues. Additionally, FACS isolation, replating, and differentiation of Osterix-Cherry+ bone marrow derived stromal cells provide evidence of their skeletal multipotency, indicated by their ability to differentiate into osteoblasts, adipocytes and chondrocytes. Based on our preliminary data, we have formulated the following hypothesis:

Osterix expression identifies a multipotent bone marrow skeletal progenitor cell population.

The goals of my thesis will be to: (1) characterize Osterix reporter expression during skeletal development and (2) characterize the bone marrow cell population expressing the Osterix reporter gene.

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