Lactate Efflux From Intervertebral Disc Cells Is Required for Maintenance of Spine Health

Elizabeth S. Silagi, Emanuel J. Novais, Sara Bisetto, Aristeidis G. Telonis, Joseph Snuggs, Christine L. Le Maitre, Yunping Qiu, Irwin J. Kurland, Irving M. Shapiro, Nancy J. Philp, Makarand V. Risbud

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Maintenance of glycolytic metabolism is postulated to be required for health of the spinal column. In the hypoxic tissues of the intervertebral disc and glycolytic cells of vertebral bone, glucose is metabolized into pyruvate for ATP generation and reduced to lactate to sustain redox balance. The rise in intracellular H+/lactate concentrations are balanced by plasma-membrane monocarboxylate transporters (MCTs). Using MCT4 null mice and human tissue samples, complemented with genetic and metabolic approaches, we determine that H+/lactate efflux is critical for maintenance of disc and vertebral bone health. Mechanistically, MCT4 maintains glycolytic and tricarboxylic acid (TCA) cycle flux and intracellular pH homeostasis in the nucleus pulposus compartment of the disc, where hypoxia-inducible factor 1α (HIF-1α) directly activates an intronic enhancer in SLC16A3. Ultimately, our results provide support for research into lactate as a diagnostic biomarker for chronic, painful, disc degeneration.

Original languageEnglish (US)
Pages (from-to)550-570
Number of pages21
JournalJournal of Bone and Mineral Research
Volume35
Issue number3
DOIs
StatePublished - Mar 1 2020

Keywords

  • BONE QCT/μCT
  • GENETIC ANIMALS MODELS
  • NUTRITION
  • TRANSCRIPTION FACTORS

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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    Silagi, E. S., Novais, E. J., Bisetto, S., Telonis, A. G., Snuggs, J., Le Maitre, C. L., Qiu, Y., Kurland, I. J., Shapiro, I. M., Philp, N. J., & Risbud, M. V. (2020). Lactate Efflux From Intervertebral Disc Cells Is Required for Maintenance of Spine Health. Journal of Bone and Mineral Research, 35(3), 550-570. https://doi.org/10.1002/jbmr.3908