| Cellular therapy holds tremendous potential in regeneration of mineralized tissues such as bones and teeth. I have characterized and identified pericytes as a unique population of dental pulp stem cells (DPSCs) that can be sorted by CD146+CD34-CD45-CD56-, expanded in culture, and differentiated into osteogenic, chondrogenic, and adipogenic lineages. A well-characterized stem cell source and an appropriate microenvironment containing growth factors and/or extracellular matrix (ECM) proteins to stimulate differentiation and mineralization are required for successful cellular therapies. To understand cell-ECM protein interaction, I studied the signaling role of phosphophoryn (PP), an ECM protein found in dentin and bone. PP signals through integrins, mitogen activated protein kinase (MAPK), and Smad pathways. There is also signaling crosstalk between the MAPK and Smad pathways. To better understand the complex signaling pathways involved in stem cell differentiation during dentin or bone formation, I have utilized quantitative proteomic strategies to study stem cell differentiation triggered by PP and BMP-2. Proteins upregulated and downregulated during differentiation were identified by mass spectrometry. With the ultimate goal of better enabling the regeneration of diseased or damaged mineralized tissue, my findings in this study have enhanced our understanding in stem cell differentiation to the osteoblastic/odontoblastic lineages and lay foundations for the development of future craniofacial regeneration. |
