Project Summary/Abstract: Intramembranous bone regeneration is a carefully orchestrated process of
hematoma formation, inflammation, and blood vessel formation and invasion, which are necessary for bone to
form. Among these, a lack of proper blood vessel formation and invasion has been identified as one of the
factors leading to a failure of orthopaedic, dental, or biomimetic implant placements, all of which are dependent
on the success of intramembranous bone regeneration. Therefore, the goal of this proposal is to gain
enhanced understanding of vasculogenic or angiogenic processes that occur during intramembranous bone
regeneration and explore the endothelial cell plasticity that could lead to novel therapeutic opportunities for
several orthopaedic or dental procedures. The current knowledge and preliminary studies for this proposal
indicate that both vasculogenesis (new blood vessel formation in the absence of vascular template) and
angiogenesis (new blood vessel formation by sprouting from existing blood vessels) occur during
intramembranous bone regeneration. Also, endothelial cells exhibit plasticity where the cells undergo
endothelial-to-mesenchymal transition (EndMT) within the regenerating bone. Thus, these novel findings set
the scientific premise to the central hypothesis that EndMT is integral to intramembranous bone regeneration.
To address this hypothesis, we propose to determine the role of EndMT during vasculogenesis and
angiogenesis in intramembranous bone regeneration by 1) examining EndMT of fluorescently labeled
endothelial cells and 2) determining the effect of EndMT inhibition on regenerating bone. Successful
completion of the proposed studies will provide novel insights regarding the role of EndMT in intramembranous
bone regeneration that can lead to therapeutic opportunities to enhance orthopaedic and dental care.
