Premium
Lactate Efflux From Intervertebral Disc Cells Is Required for Maintenance of Spine Health
Author(s) -
Silagi Elizabeth S,
Novais Emanuel J,
Bisetto Sara,
Telonis Aristeidis G,
Snuggs Joseph,
Le Maitre Christine L,
Qiu Yunping,
Kurland Irwin J,
Shapiro Irving M,
Philp Nancy J,
Risbud Makarand V
Publication year - 2020
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3908
Subject(s) - glycolysis , citric acid cycle , monocarboxylate transporter , intervertebral disc , microbiology and biotechnology , intracellular , biochemistry , flux (metallurgy) , biology , chemistry , metabolism , transporter , anatomy , gene , organic chemistry
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.