BMP Signaling and Mechanical Loading Collaborate to Alter the Structure of Osteocytes, Bone Mass Regulatory Cells – UROP Symposium

BMP Signaling and Mechanical Loading Collaborate to Alter the Structure of Osteocytes, Bone Mass Regulatory Cells

Sara Plante

Pronouns: she/her

Research Mentor(s): Yuji Mishina
Research Mentor School/College/Department: Biological and Material Sciences / Dentistry
Program:
Authors: Sara Plante, Jackson Albright, Yuji Mishina
Session: Session 4: 1:40 pm – 2:30 pm
Poster: 105

Abstract

This study is a continuation of previous work done to determine the role bone morphogenetic protein (BMP) plays in endogenic bone formation and resorption. It has been discovered that BMP is crucial in regulating bone mass through the RANKL-OPG pathway and control of Wnt signaling through the protein sclerostin. Furthermore, BMP receptor 1A (BMPR1A) disruption improves biomechanical properties. Interestingly, Bmpr1a knockout mice responded to mechanical loading to increase bone mass to a higher degree than that of wild-type mice. In this project, we are analyzing the change in the structure of osteocytes due to mechanical loading and loss of BMP signaling, as it is believed that osteocytes release sclerostin and have a regulatory purpose on bone remodeling. We are using a mouse model with six different experimental groups: wild-type and BMPR1A conditional knock-out (cKO) mice at nine weeks old, then at twelve weeks old without exercise, and at twelve weeks old with 3-weeks of exercise starting at nine weeks. By comparing the genetic control group (wild-type) to the mutant group, and by comparing the non-exercise group to the exercised group, we can analyze the individual effects that BMP and mechanical loading have on osteocyte structure, along with their combined effects. We use Focused Ion Beam-Transparent Electron Microscopy (FIB-TEM) to collect 2-dimensional (2D) images of osteocytes from each group and utilize the software program Amira to convert these 2D images into 3D models. Our current hypothesis is that osteocytes in the mutant cKO mice have a rounder shape compared to the elongated osteocytes in the wild-type mice, as this is what can be concluded from the 2D images previously analyzed. By using the Amira software, we hope to find that this hypothesis holds in 3D. This research has implications for treating bone disorders and fractures. By further understanding the regulation of bone structure by interactions between BMP and mechano-loading, we can use these regulation pathways to develop or improve treatments for bone diseases and defects affecting the population.

Biomedical Sciences

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