Lactate Efflux From Intervertebral Disc Cells Is Required for Maintenance of Spine Health.
Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA, USA.
Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Computational Medicine Center, Sidney Kimmel Medical College Thomas Jefferson University, Philadelphia, PA, USA.
Biomolecular Sciences Research Centre Sheffield Hallam University, Sheffield, UK.
Department of Medicine, Fleischer Institute for Diabetes and Metabolism Albert Einstein College of Medicine, Bronx, NY, USA.
- Published Article
Journal of Bone and Mineral Research
Wiley (John Wiley & Sons)
- Publication Date
Nov 06, 2019
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. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
This record was last updated on 12/31/2019 and may not reflect the most current and accurate biomedical/scientific data available from NLM.
The corresponding record at NLM can be accessed at https://www.ncbi.nlm.nih.gov/pubmed/31692093