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

Overview

Journal J Bone Miner Res

Publisher Oxford University Press

Date 2019 Nov 7

PMID 31692093

Citations 34

Authors

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

Affiliations

Soon will be listed here.

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. © 2019 American Society for Bone and Mineral Research.

Citing Articles

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