ArticleArthritis research & therapy2021
Lactate oxidative phosphorylation by annulus fibrosus cells: evidence for lactate-dependent metabolic symbiosis in intervertebral discs.
Article in Arthritis research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 27 citations in OpenAlex.
- The emerging role of lactate in skeletal homeostasis and disorders: Integrated mechanisms and translational opportunities.Journal of orthopaedic translation · 2026Review
- Loss of MCT1 mediated lactate uptake causes delayed endplate maturation and intervertebral disc degeneration.Cell death & disease · 2026Article
- Diagnostic Features of Discogenic Low Back Pain: A Narrative Review and Suggested Areas for Future Research and Clinical Practice.JOR spine · 2026Review
- Defining the Human Nucleus Pulposus Microenvironment and Its Impact on Cell Matrix Synthesis and Metabolic Activity.JOR spine · 2026Article
- CEST MRI: Translational prospects for intervertebral disc degeneration - from basic research to clinical applications.Journal of orthopaedic translation · 2026Review
- Lactate Metabolism in the Intervertebral Disc: Mechanistic Insights and Pathological Implications.Biomolecules · 2026Review
- Optimization and comparison of different methods for assessing cell viability in intervertebral disc organ cultures.Frontiers in bioengineering and biotechnology · 2026Article
- Lactate Metabolism in Intervertebral Disc Degeneration: Unveiling Novel Mechanisms Through Bioinformatics.JOR spine · 2025Article
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- ASIC1a mediated nucleus pulposus cells pyroptosis and glycolytic crosstalk as a molecular basis for intervertebral disc degeneration.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Lactate and lactylation in intervertebral disc degeneration.Frontiers in molecular biosciences · 2025Review
- Identification and Experimental Verification of Potential Immune Cell-Associated Gene Biomarkers in Human Intervertebral Disc Degeneration.Journal of pain research · 2025Article
- The Warburg Effect Reinterpreted 100 yr on: A First-Principles Stoichiometric Analysis and Interpretation from the Perspective of ATP Metabolism in Cancer Cells.Function (Oxford, England) · 2024Article
- Altered Metabolism and Inflammation Driven by Post-translational Modifications in Intervertebral Disc Degeneration.Research (Washington, D.C.) · 2024Article
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- Molecular pathogenicity of 1-nonadecene and L-lactic acid, unique metabolites in radicular cysts and periapical granulomas.Scientific reports · 2023Article
- Metabolic Biomarkers Differentiate a Surgical Intervertebral Disc from a Nonsurgical Intervertebral Disc.International journal of molecular sciences · 2023Article
- GLUT1 is redundant in hypoxic and glycolytic nucleus pulposus cells of the intervertebral disc.JCI insight · 2023Article
- Nutrient metabolism of the nucleus pulposus: A literature review.North American Spine Society journal · 2023Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundIntervertebral disc degeneration contributes to low back pain. The avascular intervertebral disc consists of a central hypoxic nucleus pulpous (NP) surrounded by the more oxygenated annulus fibrosus (AF). Lactic acid, an abundant end-product of NP glycolysis, has long been viewed as a harmful waste that acidifies disc tissue and decreases cell viability and function. As lactic acid is readily converted into lactate in disc tissue, the objective of this study was to determine whether lactate could be used by AF cells as a carbon source rather than being removed from disc tissue as a waste byproduct.
methodsImport and conversion of lactate to tricarboxylic acid (TCA) cycle intermediates and amino acids in rabbit AF cells were measured by heavy-isotope (
resultsHeavy-isotope tracing experiments revealed that AF cells imported and converted lactate into TCA cycle intermediates and amino acids using in vitro cell culture and in vivo models. Addition of exogenous lactate (4 mM) in culture media induced expression of the lactate importer MCT1 and increased oxygen consumption rate by 50%, mitochondrial ATP-linked respiration by 30%, and collagen synthesis by 50% in AF cell cultures grown under physiologic oxygen (2-5% O
conclusionsThese findings support disc lactate-dependent metabolic symbiosis in which lactate produced by the hypoxic, glycolytic NP cells is utilized by the more oxygenated AF cells via oxidative phosphorylation for energy and matrix production, thus shifting the current research paradigm of viewing disc lactate as a waste product to considering it as an important biofuel. These scientifically impactful results suggest novel therapeutic targets in disc metabolism and degeneration.
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