Date of Award
Jessica Cottrell, Ph.D.
Cosimo Antonacci, Ph.D.
Angela V. Klaus, Ph.D.
bone, fracture healing, endochondral ossification, insulin, zinc chloride, VEGF
Researchers have begun investigating whether insulin mimetics such as ZnCl2 could promote bone healing in both non-diabetic and diabetic fracture healing similarly to insulin. Our research focused on understanding the mechanism by which ZnCl2 affects chondrogenesis, an important component of bone fracture healing. The increases in proteoglycan deposition and cell proliferation seen in our data may be a result of ZnCl2 induction of the IGF-1 pathway. When the VEGF pathway was inhibited in ZnCl2- or insulin-treated cells significant decreases in proteoglycan deposition occurred on day 7 and 14 (P=0.007 for ZnCl2, P=0.028 for insulin) when compared to controls. This data suggests that in the presence of VEGF that Runx1 may be an important mediator in ZnCl2- mediated chondrogenesis. We believe that ZnCl2 may be upregulating many members of the collagen family and BMP-6 which insulin is not. Our data demonstrates that at later timepoints, VEGF inhibition produces higher amounts of genes such as jun, grb2, and cyclin D1 which were identified in the NGS data and confirmed through QPCR. Although the mechanisms by which ZnCl2 and insulin have been shown to overlap, our data suggests that ZnCl2 works through a mechanism different then insulin when employing the VEGF- pathway.
Sharp, Gilbert M. IV, "Zinc Chloride Enhanced Chondrogenesis is VEGF Dependent" (2019). Seton Hall University Dissertations and Theses (ETDs). 2673.