Combining Targeted Metabolomic Data with a Model of Glucose Metabolism: Toward Progress in Chondrocyte Mechanotransduction

PLoS One. 2017 Jan 5;12(1):e0168326. doi: 10.1371/journal.pone.0168326. eCollection 2017.

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.

MeSH terms

  • Chondrocytes / metabolism*
  • Chondrocytes / physiology*
  • Computational Biology
  • Glucose / metabolism
  • Humans
  • Mechanotransduction, Cellular
  • Metabolomics
  • Models, Theoretical

Substances

  • Glucose

Grants and funding

Funding was provided by NIH P20GM10339405S1 (www.nih.gov) to RKJ, NSF 1342420 and 1554708 (www.nsf.gov) to RKJ, and Montana State University (www.montana.edu) to RKJ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.