@article{f1c20630885c418cbf8f419365078439,
title = "Lactate Efflux From Intervertebral Disc Cells Is Required for Maintenance of Spine Health",
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.",
keywords = "BONE QCT/μCT, GENETIC ANIMALS MODELS, NUTRITION, TRANSCRIPTION FACTORS",
author = "Silagi, {Elizabeth S.} and Novais, {Emanuel J.} and Sara Bisetto and Telonis, {Aristeidis G.} and Joseph Snuggs and {Le Maitre}, {Christine L.} and Yunping Qiu and Kurland, {Irwin J.} and Shapiro, {Irving M.} and Philp, {Nancy J.} and Risbud, {Makarand V.}",
note = "Funding Information: This work was supported by grants from the NIH R01 AR055655, AR064733, AR074813 (to MVR), R01 EY012042 (to NJP), and a Sheffield Hallam University Vice Chancellors Scholarship (to CLM). Elizabeth Silagi is supported by T32 AR052273. The Stable Isotope and Metabolomics Core Facility of the Diabetes Research and Training Center (DRTC) of the Albert Einstein College of Medicine is supported by NIH/NCI grant (P60DK020541). Authors{\textquoteright} roles: ESS, SB, NJP, IMS, and MVR conceived the study. ESS conducted the experiments, analyzed data, and wrote the manuscript. EJN, SB, AGT, JS, CLM, YQ and IJK conducted experiments. IMS and MVR secured funding and wrote the manuscript. IJK, CLM, and NJP also secured funding. All authors reviewed the results and approved the final version of the manuscript. Funding Information: This work was supported by grants from the NIH R01 AR055655, AR064733, AR074813 (to MVR), R01 EY012042 (to NJP), and a Sheffield Hallam University Vice Chancellors Scholarship (to CLM). Elizabeth Silagi is supported by T32 AR052273. The Stable Isotope and Metabolomics Core Facility of the Diabetes Research and Training Center (DRTC) of the Albert Einstein College of Medicine is supported by NIH/NCI grant (P60DK020541). Authors? roles: ESS, SB, NJP, IMS, and MVR conceived the study. ESS conducted the experiments, analyzed data, and wrote the manuscript. EJN, SB, AGT, JS, CLM, YQ and IJK conducted experiments. IMS and MVR secured funding and wrote the manuscript. IJK, CLM, and NJP also secured funding. All authors reviewed the results and approved the final version of the manuscript. Publisher Copyright: {\textcopyright} 2019 American Society for Bone and Mineral Research",
year = "2020",
month = mar,
day = "1",
doi = "10.1002/jbmr.3908",
language = "English (US)",
volume = "35",
pages = "550--570",
journal = "Journal of Bone and Mineral Research",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "3",
}
