Hayden Debeer
Pronouns: she/her
Research Mentor(s): Yadav Wagley
Research Mentor School/College/Department: Orthopaedic Surgery / Medicine
Program:
Authors: Hayden Debeer, Kurt D. Hankenson, Yadav Wagley
Session: Session 6: 3:40 pm – 4:30 pm
Poster: 89
Abstract
Osteoporosis affects approximately 10 million Americans. It is characterized by low bone mineral density (BMD) which causes the bones to be more susceptible to fractures. Osteoporosis treatments and therapies are limited. Awareness about bone diseases and their causal mechanisms are especially important as they lead to many other illnesses and health issues as they restrict mobility. Bone mineral density is cumulatively affected by the balanced activity of the bone depositing osteoblasts and bone resorbing osteoclasts. In the case of osteoporosis, osteoclastic bone resorption occurs at an increased rate which causes the bones to become brittle and lose mineralisation. Several genes are known to be associated with osteoporosis. In particular, the EPDR1 gene was recently discovered to play an important role during human osteoblast differentiation. In absence of EPDR1, human osteoblast progenitors take an inflammatory phenotype suggesting a role in immune regulation. The purpose of this study is to evaluate whether EPDR1 has a direct functional role in osteoclast cells which are derived from cells of the immune lineage. Our preliminary data shows that when THP-1 human monocyte cells differentiate into macrophages, EPDR1 gene expression decreases with concurrent increase in other macrophage gene markers such as MMP9, NFATc1, and CATK. We hypothesize that the downregulation of EPDR1 is essential for the differentiation of human progenitor cells into osteoclasts. In further experiments, we knocked down the expression of the EPDR1 gene using small interfering RNA (siRNA) and induced the gene silenced cells to undergo macrophage differentiation. However, EPDR1 silencing showed minimal effects on the overall differentiation of THP-1 cells into macrophages. In future works, we plan to over-express EPDR1 as well as evaluate the sustained presence of the EPDR1 protein on the THP-1 cell differentiation program. We hypothesize that the sustained activity of the EPDR1 protein is counterintuitive to the osteoclast differentiation. Through our future work, we aim to dissect the role of EPDR1 protein in both osteoblast and osteoclast settings in vivo and to establish it as a critical gene for BMD maintenance during aging and osteoporosis progression.
