Published:
[Erscheinungsort nicht ermittelbar]: eScholarship, University of California, 2017
Language:
English
Origination:
University thesis:
Dissertation, eScholarship, University of California, 2017
Footnote:
Description:
In the search for novel therapies in regenerative medicine, there has been an increasing interest in a small subset of cells that originate from the mesoderm known as mesenchymal stem cells (MSCs). MSCs prove to be a promising tool due to their potential to repair or regenerate damaged tissues. They are also capable of self-renewal and differentiating into mesoderm lineages, such as chondrocytes, osteocytes and adipocytes, but can also differentiate into ectodermic and endodermic cells. MSCs are extensively distributed in a wide range of postnatal tissue types and have been successfully isolated from orofacial tissues. MSCs derived from craniofacial tissues including dental mesenchymal stem cells (DMSCs) can be isolated and have the potential for use in tissue engineering, including dental tissue, nerve and bone regeneration. Dental pulp stem cells, also known as DPSCs, can differentiate into cell types such as odontoblasts, osteoblasts, chondrocytes, cardiomyocytes, adipocytes, neuron cells, corneal epithelial cells, melanoma cells and insulin-secreting Beta cells; differentiation can be modulated with growth factors, transcriptional factors, extracellular matrix proteins and receptor molecules in the local microenvironment. The neurotrophin nerve growth factor (NGF) is important in the development and maintenance of sympathetic and sensory neurons, and its ability to promote mineralization also makes it an appealing candidate in bone and tissue regeneration. In this study, we wanted to investigate the molecular regulation of NGF-mediated osteogenic differentiation of MSCs from dental pulp. We found that exogenous treatment with NGF led to an increase in alkaline phosphatase (ALP) expression and activity; there was also an increase in alizarin red staining (ARS) and its quantification of calcium mineral deposition. We also observed a strong induction of mRNA expression of osteogenic genes: BSP, DLX5, OCN, OPN, and RUNX2. This treatment also led to the upregulation of the JNK and c-Jun signaling pathways in a time-dependent manner. Furthermore, we used a JNK inhibitor to evaluate the role of JNK in the osteogenic pathway and observed a decrease in osteogenic differentiation. The present study aims to better understand the molecular pathways involved in regulating NGF-mediated osteogenic differentiation of MSCs and may be useful in the development of an effective application in regenerative medicine.