Erin Meymarian
Research Mentor(s): Yadav Wagley
Mentor Department: Orthopaedic Surgery
Authors: Erin Meymarian, Buchan Jiang, Yadav Wagley, Kurt Hankenson
Session: Session 7 (4:00pm – 4: 50pm)
Presentation Type: Poster 13
Abstract
While the musculoskeletal system has several mechanisms for regeneration after it is damaged, critical-size bone defects present with great difficulty to ordinary repair processes. Currently, there are few treatment options available for failed bone healing, and with an increasing geriatric population, there is a demand for new therapies. Previous research has revealed the abilities of Bone Morphogenetic Proteins (BMP) to promote bone regeneration; however, BMP’s implementation in new treatments is limited due to adverse side effects. Within the Wnt signaling pathway where BMP largely resides, there is R-spondin (RSPO), a protein family responsible for positive modulation. Specifically, RSPO2 enhances the mineralization and osteoblastic differentiation induced by BMP2. Despite this fact, the complex interactions between BMP2 and RSPO2 for in vitro osteoblastogenesis and in vivo bone formation have not been thoroughly investigated. Consequently, we hypothesized that RSPO2 would amplify BMP-induced osteoblastogenesis and critical-size bone healing. In the presence of BMP2, RSPO2, or both, using Osteopermissive Media, primary bone-marrow-derived human mesenchymal stem cells (hMSC) and calvaria-derived murine pre-osteoblastic (MC3T3-E1) cells will be cultured and induced to differentiate into osteoblasts. RNA isolation, alkaline phosphatase (ALP) staining, and Alizarin red S staining (ARS) will be conducted three, five, and ten days after treatment, respectively. Our in vivo studies will examine Wnt reporter mice (TCF/Lef-H2B: GFP) treated with BMP2 and/or RSPO2. With animal care and use committee approval, bilateral calvarial defects will be created in the mice model. Then, whole calvariae will be microCT scanned and analyzed using DragonFly software. Data will be further analyzed using GraphPad Prism. This study aims to obtain a more comprehensive understanding of the interactions between RSPO2 and BMP2 that could improve treatment options for bone defects.
