Evidence map›Paper›PMID 41390678›Full record

ArticleCell death & disease2025

Disrupted bone microenvironment and immune recovery following total body irradiation in a murine model.

Tibor Sághy, Priti Gupta, Karin Horkeby, Petra Henning, Claes Ohlsson, Carmen Corciulo, Marie K Lagerquist, Andrei S Chagin, Cecilia Engdahl

Abstract read
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Tibor SághyDepartment of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Priti GuptaDepartment of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Karin HorkebyDepartment of Internal Medicine and Clinical Nutrition, Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Petra HenningDepartment of Internal Medicine and Clinical Nutrition, Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Claes OhlssonDepartment of Internal Medicine and Clinical Nutrition, Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Carmen CorciuloDepartment of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-1865-3494
Marie K LagerquistDepartment of Internal Medicine and Clinical Nutrition, Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Andrei S ChaginDepartment of Internal Medicine and Clinical Nutrition, Sahlgrenska Osteoporosis Centre and Centre for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.ORCID http://orcid.org/0000-0002-2696-5850
Cecilia EngdahlDepartment of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. cecilia.engdahl@gu.se.ORCID http://orcid.org/0000-0002-8914-0178

Funding

Vetenskapsrådet (Swedish Research Council) 2019-01852
6 · The paper itself

Abstract

Irradiation is an effective therapy for eliminating cancer cells and serves as a critical preparative regimen for hematopoietic stem cell transplantation (HSCT). However, irradiation affects healthy tissue, disrupting bone tissue and bone marrow homeostasis, which leads to skeletal and immune dysfunction. To investigate these effects, we used a female murine model to explore the mechanisms underlying the skeletal damage caused by total body irradiation. Experiments were carried out over a 12-week period of total body irradiation and HSCT, supplemented by an acute study involving only total body irradiation and osteoclastogenesis. Irradiation resulted in a depletion of bone marrow immune cells, followed by an increase in bone marrow cellularity 12 weeks after irradiation and HSCT compared to naive controls, indicating late-stage local immune induction. Cortical and trabecular bone loss appeared 2 weeks post-irradiation and HSCT and persisted throughout the study. This bone damage was accompanied by a sustained increase in apoptotic cells in the bone marrow within 6 h post-irradiation and persisted for up to 12 weeks after irradiation and HSCT. This was coupled with elevated local expression of the pro-apoptotic Bax gene and an increase in TGF-β1, a gene associated with the clearance of apoptotic cells. In vitro studies demonstrated that macrophages and pre-osteoclasts, but not fully differentiated osteoclasts, efficiently cleared apoptotic cells, resulting in increased levels of TGF-β1 in the culture supernatant. While the clearance of apoptotic cells and associated TGF-β1 signaling were evident, their direct role in skeletal outcomes remains unclear. These findings suggest that persistent apoptotic cells contribute to impaired bone remodeling, potentially affecting osteoclast function and the bone microenvironment. Additional research is needed to investigate whether targeting apoptotic cell clearance can mitigate bone damage and promote skeletal recovery following irradiation.

Indexed as

Bone and BonesWhole-Body IrradiationAnimalsApoptosisbcl-2-Associated X ProteinBone MarrowFemaleHematopoietic Stem Cell TransplantationMiceMice, Inbred C57BLOsteoclastsOsteogenesisTransforming Growth Factor beta1bcl-2-Associated X ProteinTransforming Growth Factor beta1

Identifiers

PMID41390678
PMCPMC12847818

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.