Back

Lactate metabolic coupling between the endplates and nucleus pulposus via MCT1 is essential for intervertebral disc health

Tsingas, M.; Tsingas, K.; Zhang, W.; Goldman, A. R.; Risbud, M. V.

2025-02-25 cell biology
10.1101/2025.02.24.640004 bioRxiv
Show abstract

During skeletal growth, there is an increased secretion of lactate by glycolytic nucleus pulposus (NP) cells of the intervertebral disc. To investigate the role of this anion, we generated annulus fibrosus (AF) and endplate (EP) specific Mct1cKO (Slc16a1Col2CreERT2) mice. Histological and spatial transcriptomic studies indicated significant disc degeneration in Mct1cKO, characterized by NP cell loss and delayed EP maturation. Metabolic assays showed that while AF and EP cells were glycolytic, EP chondrocytes readily metabolized lactate. In EP cells, lactate promoted protein, and H3K18 lactylation, implying epigenetic programming. These findings suggest that NP-derived lactate promotes EP cartilage transdifferentiation into the subchondral bone, and in its absence, continued glucose consumption by the persistent EP cartilage reduces glucose availability to the NP and AF likely contributing to tissue degeneration. This study provides the first in vivo evidence that metabolic coupling between NP and EP cells is essential for disc growth and health.

Matching journals

The top 7 journals account for 50% of the predicted probability mass.

1
The FASEB Journal
○ 194 papers in training set
Top 0.1%
15.1%
Similar papers in this journal
2
eLife
● 5828 papers in training set
Top 6%
12.7%
Similar papers in this journal
3
Cell Death & Disease
147 papers in training set
Top 0.3%
6.3%
4
Science Advances
● 1243 papers in training set
Top 3%
6.3%
Similar papers in this journal
5
Journal of Biological Chemistry
○ 690 papers in training set
Top 2%
4.9%
Similar papers in this journal
6
JCI Insight
● 277 papers in training set
Top 2%
4.0%
7
American Journal of Physiology-Cell Physiology
● 39 papers in training set
Top 0.2%
3.4%
50% of probability mass above
8
Frontiers in Cell and Developmental Biology
○ 233 papers in training set
Top 1%
3.2%
9
Cell Communication and Signaling
○ 51 papers in training set
Top 0.3%
2.4%
10
Cells
○ 249 papers in training set
Top 2%
2.1%
11
Journal of Bone and Mineral Research
◐ 35 papers in training set
Top 0.2%
1.9%
12
International Journal of Molecular Sciences
○ 494 papers in training set
Top 8%
1.7%
13
Matrix Biology
○ 29 papers in training set
Top 0.3%
1.7%
14
Nature Communications
○ 5641 papers in training set
Top 44%
1.7%
15
iScience
○ 1154 papers in training set
Top 17%
1.7%
16
Glia
○ 81 papers in training set
Top 0.8%
1.7%
17
Communications Biology
○ 993 papers in training set
Top 19%
1.3%
18
Frontiers in Endocrinology
○ 58 papers in training set
Top 1%
1.1%
19
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 34%
1.1%
20
Scientific Reports
○ 3612 papers in training set
Top 66%
1.1%
21
PLOS Genetics
● 862 papers in training set
Top 10%
1.0%
22
Advanced Science
○ 286 papers in training set
Top 8%
1.0%
23
PLOS ONE
● 5266 papers in training set
Top 55%
1.0%
24
American Journal of Physiology-Lung Cellular and Molecular Physiology
● 43 papers in training set
Top 0.6%
1.0%
25
Life Science Alliance
● 285 papers in training set
Top 8%
0.8%
26
Osteoarthritis and Cartilage
○ 32 papers in training set
Top 0.3%
0.8%
27
Cellular and Molecular Life Sciences
○ 96 papers in training set
Top 2%
0.8%
28
Frontiers in Immunology
○ 638 papers in training set
Top 9%
0.8%
29
Cell Reports
○ 1498 papers in training set
Top 27%
0.8%
30
Journal of Molecular and Cellular Cardiology
○ 40 papers in training set
Top 0.7%
0.8%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.