Physiological dynamic compression regulates central energy metabolism in primary human chondrocytes
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Chondrocytes use the pathways of central metabolism to synthesize molecular building blocks and energy for cartilage homeostasis. An interesting feature of the in vivo chondrocyte environment is the cyclical loading generated in various activities (e.g., walking). However, it is unknown whether central metabolism is altered by mechanical loading. We hypothesized that physiological dynamic compression alters central metabolism in chondrocytes to promote production of amino acid precursors for matrix synthesis. We measured the expression of central metabolites (e.g., glucose, its derivatives, and relevant co-factors) for primary human osteoarthritic chondrocytes in response to 0–30 minutes of compression. To analyze the data, we used principal components analysis and ANOVA-simultaneous components analysis, as well as metabolic flux analysis. Compression-induced metabolic responses consistent with our hypothesis. Additionally, these data show that chondrocyte samples from different patient donors exhibit different sensitivity to compression. Most importantly, we find that grade IV osteoarthritic chondrocytes are capable of synthesizing non-essential amino acids and precursors in response to mechanical loading. These results suggest that further advances in metabolic engineering of chondrocyte mechanotransduction may yield novel translational strategies for cartilage repair.
KeywordsOsteoarthritis Cartilage repair Mechanotransduction Chondrocyte Systems biology Metabolic flux analysis
This study was funded by the National Science Foundation (1342420, 1554708 and 1542262) and the NIH (P20GM103474).
Compliance with ethical standards
Conflicts of interest
The authors have received license fees from technology used in this project. The corresponding author has a financial interest in a company that licensed the metabolic flux analysis technology.
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