title: Combining Targeted Metabolomic Data with a Model of Glucose Metabolism: Toward Progress in Chondrocyte Mechanotransduction.
abstract: Osteoarthritis is a debilitating disease likely involving altered metabolism of the chondrocytes in articular cartilage. Chondrocytes can respond metabolically to mechanical loads via cellular mechanotransduction, and metabolic changes are significant because they produce the precursors to the tissue matrix necessary for cartilage health. However, a comprehensive understanding of how energy metabolism changes with loading remains elusive. To improve our understanding of chondrocyte mechanotransduction, we developed a computational model to calculate the rate of reactions (i.e. flux) across multiple components of central energy metabolism based on experimental data. We calculated average reaction flux profiles of central metabolism for SW1353 human chondrocytes subjected to dynamic compression for 30 minutes. The profiles were obtained solving a bounded variable linear least squares problem, representing the stoichiometry of human central energy metabolism. Compression synchronized chondrocyte energy metabolism. These data are consistent with dynamic compression inducing early time changes in central energy metabolism geared towards more active protein synthesis. Furthermore, this analysis demonstrates the utility of combining targeted metabolomic data with a computational model to enable rapid analysis of cellular energy utilization.
authors.affiliation: Computer Science, Montana State University, Bozeman, MT United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Salinas
authors.affiliation: Mathematics, Montana State University, Bozeman, MT United States of America.
authors.forename: Cody A
authors.identifier: http://orcid.org/0000-0002-0259-7037
authors.initials: CA
authors.lastname: Minor
authors.affiliation: Chemical & Biological Engineering, Montana State University, Bozeman, MT United States of America.
authors.forename: Ross P
authors.initials: RP
authors.lastname: Carlson
authors.affiliation: Mechanical & Industrial Engineering, Montana State University, Bozeman, MT United States of America.
authors.forename: Carley N
authors.initials: CN
authors.lastname: McCutchen
authors.affiliation: Computer Science, Montana State University, Bozeman, MT United States of America.
authors.forename: Brendan M
authors.identifier: http://orcid.org/0000-0001-7151-2124
authors.initials: BM
authors.lastname: Mumey
authors.affiliation: Mechanical & Industrial Engineering, Montana State University, Bozeman, MT United States of America.|Department of Cell Biology & Neurosciences, Montana State University, Bozeman, MT United States of America.|Department of Orthopaedics and Sports Medicine, University of Washington, Seattle, WA United States of America.
authors.forename: Ronald K
authors.identifier: http://orcid.org/0000-0003-0752-4109
authors.initials: RK
authors.lastname: June
mesh_terms: D019902:Chondrocytes / Q000378:metabolism* / Q000502:physiology*; D019295:Computational Biology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular; D055432:Metabolomics; D008962:Models, Theoretical
chemical_list: D005947:Glucose