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.

中文翻译：

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椎间盘细胞的乳酸流出是维持脊柱健康所必需的。

维持糖酵解代谢被认为是脊柱健康所必需的。在椎间盘缺氧组织和椎骨糖酵解细胞中，葡萄糖被代谢为丙酮酸以生成ATP，并被还原为乳酸以维持氧化还原平衡。细胞内H + /乳酸浓度的升高通过血浆膜单羧酸盐转运蛋白（MCT）来平衡。使用MCT4空小鼠和人体组织样本，再加上遗传和代谢方法，我们确定H + /乳酸外排对于维持椎间盘和椎骨健康至关重要。从机制上讲，MCT4维持椎间盘髓核腔内的糖酵解和三羧酸（TCA）循环通量和细胞内pH稳态，其中缺氧诱导因子1α（HIF-1α）直接激活SLC16A3中的内含子增强子。最终，我们的结果为乳酸作为慢性，疼痛性椎间盘退变的诊断生物标志物的研究提供了支持。©2019美国骨骼和矿物质研究学会。