Journal article
Loss of MCT1 mediated lactate uptake causes delayed endplate maturation and intervertebral disc degeneration
Cell death & disease, v 17(1), p698
03 Jun 2026
PMID: 42236482
Abstract
During skeletal growth, it is thought that the lactate secreted by the glycolytic nucleus pulposus (NP) cells exits the intervertebral disc into circulation via endplates. Our current studies challenge this long-held notion. Mice with early postnatal, endplate, and annulus fibrosus-specific deletion of lactate importer, MCT1, exhibited disc degeneration characterized by NP cell loss and pronounced endplate structural changes. Using metabolic and transcriptomic approaches, we demonstrate that MCT1 loss inhibits endplate chondrocyte differentiation and that lactate serves both as a crucial TCA metabolite and promotes protein and histone lactylation and gene expression. These findings suggest that during skeletal growth, NP-derived lactate in part supports endplate cartilage differentiation into the vascularized subchondral bone, which, when absent, limits nutrient exchange and availability to the other disc compartments, affecting their homeostasis. This study provides the first in vivo evidence that loss of MCT1 mediated lactate uptake in endplate cells causes delayed maturation and intervertebral disc degeneration.
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Details
- Title
- Loss of MCT1 mediated lactate uptake causes delayed endplate maturation and intervertebral disc degeneration
- Creators
- Maria Tsingas - Thomas Jefferson UniversityKonstantinos Tsingas - University of PennsylvaniaMei Smyers - Thomas Jefferson UniversityWujuan Zhang - The Wistar InstituteAaron R Goldman - The Wistar InstituteEulisa Lawrence - Thomas Jefferson UniversityJohn A Collins - Thomas Jefferson UniversityMakarand V Risbud - Thomas Jefferson University
- Publication Details
- Cell death & disease, v 17(1), p698
- Publisher
- Nature Publishing
- Number of pages
- 17
- Grant note
- R01AR082460 / U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R56 AR055655-16A1 / U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R01AG073349 / U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Drexel University
- Web of Science ID
- WOS:001842852400004
- Scopus ID
- 2-s2.0-105046661350
- Other Identifier
- 991022194942304721
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology