Micro-Macro Scale Investigations to Study Osteocyte Mechanobiology

University Of Missouri-Kansas City, Columbia MO

Investigators

Abstract

Osteoporosis is a disease of low bone mass and increased risk of fracture. Exercise can increase bone size and help protect against fractures. This project aims to improve understanding of how bone cells detect bone loading. The bone cell thought to be the load detector is called the "osteocyte". Osteocytes communicate with each other and to other cells on the surface of the bone to change bone size to match the loads on the bone. The goal of the work is to determine how bone deformation and fluid flow are detected and changed into a chemical signal that the cell uses to communicate to other cells. Mechanical loading will be related to the biological response of the cell using advanced cell biological methods. The outcomes of this research will determine the role of solid-fluid interaction mechanics in the activation of bone formation to help explain and mitigate age related bone loss. The project will offer local high school students, especially female students, one day research camps and encourage them to pursue engineering and medical education. Undergraduate students will work on various aspects of the project. The objective is to gain a better understanding of the role of multiscale mechanics - from macro-scale bone strains to micro-scale strains (local bone matrix and lacunar strain and the corresponding fluid flow shear stress on the cell membrane) in mechanotransduction at the osteocyte cellular level. We plan to study these effects using the activation of the Wnt/beta-catenin signaling pathway in osteocytes as a readout for their response to loading. This pathway is known to be important in mediating load related bone formation. The methods include experimental studies using axial loading experiments on mouse whole forearm, novel microscale axial loading experiments on murine ulna sections using the MicroXCT-200 (Carl Zeiss/Xradia) to determine lacunar strains. Newly developed multiplexed 3D confocal microscopy techniques will be used for 3D modelling of osteocytes and their lacunar fluid space for fluid-structure interaction FE models.