EFFECTS OF PARATHYROID HORMONE ANALOGUES ON
HEMATOPOIETIC STEM CELL NICHE POTENTIAL OF
BONE-MARROW MONONUCLEAR CELLS.
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirement for the Degree
MASTERS OF SCIENCE
(EXPERIMENTAL AND MOLECULAR PATHOLOGY)
Copyright 2009 Akiko Umetsu
In this study we compared the significance of different intracellular pathways in bone-marrow mononuclear cells (BMMNCs) that are implicated in their hematopoietic stem cell (HSC) support. In adult mammals, the majority of HSCs reside in the bone marrow (BM). The BM provides a specialized microenvironment called niche, composed of cells and extracellular matrix molecules that helps HSCs maintain the essential balance between self-renewal and differentiation. Previously it was shown that the HSC niche can become potentiated by parathyroid hormone (PTH) treatment. However, receptor binding of PTH triggers a wide variety of intracellular pathways in BMMNCs, namely the PKA and PKC pathways, and which pathway activation leads to better niche potential remains poorly understood. To address this question we utilized different PTH analogues that activate only one of these pathways. Results revealed that the activation of PKA rather than PKC may be more important in the BM HSC niche potential.