This Faculty Early Career Development (CAREER) Program project will investigate cartilage mechanotransduction in response to different types of forces and examine how energy is used by cartilage. Joints such as the knee or the hip are important for everyday activity like walking. These activities result in forces on the cartilage in the joint. Because more than 50 million Americans suffer from some type of joint disease, understanding how cartilage response to forces is important for improving joint function. Mechanotransduction is the process that cartilage uses to sense and respond to forces. There are many aspects of cartilage mechanotransduction that are not yet known. The results of this project will provide a foundation of information that will improve the basic understanding of how cartilage functions. The potential societal benefits include new knowledge that will help scientists and engineers develop new treatments for problems like arthritis.

Chondrocytes, the cells of cartilage, respond to mechanical loads by both known and unknown mechanisms. Metabolomic profiling describes the functional state of the cell by quantifying changes in small molecules using liquid-chromatography and mass spectrometry. The first objective of this project is to define both shared and distinct metabolomic responses for chondrocytes in shear and compressive loading. The second objective is to examine the conversion of mechanical energy from applied compression into biological energy used by chondrocytes. For these studies, human chondrocytes will be encapsulated in hydrogels of physiological stiffness. These gels will be subjected to relevant mechanical deformations, and metabolites will then be extracted. Both global and targeted metabolomic profiling will be used to analyze the responses of chondrocytes to the applied deformations. The targeted metabolomic data will be integrated into a systems model of energy metabolism, and analyses will examine how mechanical deformations alter chondrocyte energy usage. The significance of this work is that by examining both global and targeted metabolomic responses to loading, these studies will provide the knowledge necessary to design and administer loading regimes for restoring cartilage and joint health.

Project Start
Project End
Budget Start
2016-05-01
Budget End
2022-04-30
Support Year
Fiscal Year
2015
Total Cost
$614,000
Indirect Cost
Name
Montana State University
Department
Type
DUNS #
City
Bozeman
State
MT
Country
United States
Zip Code
59717