Back

Local erythropoiesis directs oxygen availability in bone fracture repair

Lang, A.; Collins, J. M.; Nijsure, M. P.; Belali, S.; Khan, M. P.; Moharrer, Y.; Schipani, E.; Yien, Y. Y.; Fan, Y.; Gelinsky, M.; Vinogradov, S. A.; Koch, C.; Boerckel, J. D.

2025-01-11 cell biology
10.1101/2025.01.10.632440 bioRxiv
Show abstract

Oxygen tension dynamically regulates stem cell fate and tissue regeneration, yet how local oxygen availability is controlled within the bone marrow niche remains poorly understood. While bone marrow injury, such as by bone fracture, disrupts marrow vasculature, the consequences on local oxygen tension remain unclear. Here, we show in mice that while the tissue oxygen tension in bone marrow is low (25 mmHg, [~]4% O2), intracellular oxygenation is heterogeneous and erythroid cells are high in oxygen. Bone fracture elevates oxygen tension in the injured bone marrow (>55 mmHg, [~]8%), which persists for over a week post-injury. This oxygen elevation results not from angiogenesis, but rather from localized expansion of erythroid precursor cells in the injured bone marrow. The activated erythroid precursors synthesize hemoglobin and accumulate oxygen, acting as local modulators of oxygen tension. Blocking transferrin receptor 1 (CD71)-mediated iron uptake impairs hemoglobin synthesis, reduces local oxygen levels, and enhances bone regeneration through increased angiogenesis and osteogenesis. These findings identify erythroid precursors as active regulators of local oxygen availability in the bone marrow niche, which may be targetable to enhance tissue regeneration.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

1
Nature Communications
○ 5641 papers in training set
Top 3%
30.1%
Similar papers in this journal
2
Science Advances
● 1243 papers in training set
Top 2%
7.6%
Similar papers in this journal
3
eLife
● 5828 papers in training set
Top 15%
7.6%
Similar papers in this journal
4
Nature
○ 645 papers in training set
Top 2%
6.5%
Similar papers in this journal
50% of probability mass above
5
Nature Cell Biology
○ 118 papers in training set
Top 0.8%
3.9%
Similar papers in this journal
6
Proceedings of the National Academy of Sciences
● 2444 papers in training set
Top 17%
3.1%
7
Cell Reports
○ 1498 papers in training set
Top 14%
2.6%
8
Blood
● 74 papers in training set
Top 0.7%
2.3%
9
Nature Immunology
○ 79 papers in training set
Top 1%
2.1%
10
Developmental Cell
○ 196 papers in training set
Top 2%
1.8%
11
Nature Aging
○ 60 papers in training set
Top 0.9%
1.8%
12
Cell Metabolism
○ 57 papers in training set
Top 0.7%
1.8%
13
Cell
○ 431 papers in training set
Top 6%
1.8%
14
Science
● 477 papers in training set
Top 5%
1.7%
15
Communications Biology
○ 993 papers in training set
Top 17%
1.5%
16
Cell Stem Cell
○ 62 papers in training set
Top 1%
1.1%
17
Cell Research
○ 51 papers in training set
Top 0.9%
1.1%
18
Current Biology
○ 665 papers in training set
Top 9%
1.1%
19
Journal of Clinical Investigation
● 179 papers in training set
Top 5%
1.1%
20
Nature Neuroscience
○ 252 papers in training set
Top 4%
1.0%
21
Nature Materials
○ 28 papers in training set
Top 0.5%
1.0%
22
The EMBO Journal
○ 309 papers in training set
Top 7%
0.8%
23
Advanced Science
○ 286 papers in training set
Top 10%
0.8%
24
Journal of Cell Biology
● 392 papers in training set
Top 4%
0.8%
25
npj Regenerative Medicine
○ 24 papers in training set
Top 0.7%
0.8%
26
Science Translational Medicine
● 127 papers in training set
Top 5%
0.6%
27
Nature Biotechnology
○ 172 papers in training set
Top 5%
0.6%
28
Science Immunology
● 88 papers in training set
Top 2%
0.6%
29
Scientific Reports
○ 3612 papers in training set
Top 79%
0.6%

"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.