Malamas Daratzis
Pronouns: he/him
Research Mentor(s): Kurt Hankenson
Co-Presenter:
Research Mentor School/College/Department: Orthopaedic Surgery / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 2 – 11am – 11:50am
Room: League Ballroom
Authors: Malamas Daratzis, Alexander Knights, Kurt Hankenson
Presenter: 67
Abstract
The Wnt/ß-catenin signaling pathway has been shown to have a direct effect on stem cells during bone regeneration, making Wnt a potential target to stimulate bone repair after trauma. Wnt signaling is important in the formation of bone, as it regulates the differentiation and maturation of bone-forming cells called osteoblasts. To study osteoblastogenesis, we use primary mouse bone marrow mesenchymal stromal cells (BMSCs), which can be differentiated in vitro to become mature osteoblasts and undergo mineral deposition, mimicking bone formation in vivo. Through studying mechanisms of osteoblastogenesis from BMSCs, a better understanding of osteogenic differentiation and gene expression can be developed, providing insights into bone regeneration and how we can therapeutically modulate this process. In this study, we modulated the Wnt signaling pathway during osteogenic differentiation of BMSCs using the Wnt activator CHIR99021, or Wnt inhibitors C59 and PKF118-310. BMSCs underwent regular osteogenic differentiation for a period of 12 days, with media being refreshed every 2-3 days. Wnt modulators were included with each media change, ensuring that cells were exposed to Wnt activation or inhibition throughout the course of their osteogenic differentiation. BMSCs were harvested at days 0, 4, 8 and 12 for RNA isolation to assess changes in gene expression at each stage of differentiation. We measured levels of genes associated with osteogenesis and osteoblast maturation, and Wnt signaling genes, to determine the direct effects of modulating Wnt signaling on Wnt pathway activation and how this functionally translates into effects on osteoblastogenesis. We observed perturbation of the Wnt pathway and osteogenesis with Wnt modulation, affecting osteoblast maturation and mineralization of BMSCs. Findings from this study shed light on the role of Wnt signaling in osteogenesis, and insights gained from these results may provide new avenues for therapeutic bone growth techniques in individuals with congenital or traumatic bone disorders.
Interdisciplinary, Natural/Life Sciences
