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Physiological dynamic compression regulates central energy metabolism in primary human chondrocytes

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Abstract

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.

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Acknowledgements

This study was funded by the National Science Foundation (1342420, 1554708 and 1542262) and the NIH (P20GM103474).

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  1. Montana State University, PO Box 173800, Bozeman, MT, 59717-3800, USA

    Daniel Salinas, Brendan M. Mumey & Ronald K. June

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  1. Daniel Salinas
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  2. Brendan M. Mumey
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  3. Ronald K. June
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Correspondence to Ronald K. June.

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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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This study was funded by the National Science Foundation (NSF 1342420, 1554708 and 1542262.).

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S1

Stoichiometric matrix used for metabolic flux analysis and flux balance analysis. An explanation of the reaction abbreviations used in the paper is included.

S2

Values for reaction fluxes over the first and second 15 minutes of compression for each donor. Fluxes that generate the third PCA axis and fluxes that generate the first ASCA axis are included.

S3

Values for PCA and ASCA decompositions of variation. The largest three components are included for PCA, and the largest two for ASCA.

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Salinas, D., Mumey, B.M. & June, R.K. Physiological dynamic compression regulates central energy metabolism in primary human chondrocytes. Biomech Model Mechanobiol 18, 69–77 (2019). https://doi.org/10.1007/s10237-018-1068-x

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  • DOI: https://doi.org/10.1007/s10237-018-1068-x

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