Evidence map›Paper›PMID 41469373›Full record

ArticleNature communications2025

Chemotherapy-induced adipo-lineage cell senescence drives bone loss.

Ganesh Kumar Raut, Taylor Malachowski, Anupama Melam, Renata Ramalho-Oliveira, Taylor Holt, Xianmin Luo, Zhangting Yao, Douglas V Faget, Qihao Ren, David G DeNardo and 1 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
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

11 authors.

Ganesh Kumar RautDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.
Taylor MalachowskiDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.
Anupama MelamDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-1000-5273
Renata Ramalho-OliveiraDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.
Taylor HoltCollege of Arts and Sciences, Washington University, St. Louis, MO, USA.
Xianmin LuoDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.
Zhangting YaoDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.
Douglas V FagetDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-2452-0962
Qihao RenDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-5178-1829
David G DeNardoDepartment of Medicine, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-3655-5783
Sheila A StewartDepartment of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA. sheila.stewart@wustl.edu.ORCID http://orcid.org/0000-0002-2260-9576

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN · 2001 to 2026
$128.0M
Resource Based Center for Musculoskeletal Biology and Medicine (Overall Application)P30AR074992 · NIAMS · WASHINGTON UNIVERSITY · PI MATTHEW J SILVA · 2019 to 2026
$6.8M
Skeletal Disorders Training ProgramT32AR060719 · NIAMS · WASHINGTON UNIVERSITY · PI Roberto Civitelli · 2011 to 2026
$4.6M
Stomal Senescence Regulator of Tumor Immunity and ProgressionR01CA286615 · NCI · WASHINGTON UNIVERSITY · PI David G DeNardo, Paolo Provenzano · 2024 to 2026
$3.2M
Synergized Immune and Tumor Cell Bone Marrow Biomarkers to Predict Recurrence in Triple Negative Breast CancerR01CA262555 · NCI · WASHINGTON UNIVERSITY · PI AFT, REBECCA L., DENARDO, DAVID G · 2021 to 2025
$3.2M
MICROENVIRONMENTAL CONTROLS OF TUMOR DORMANCYR01AG059244 · NIA · WASHINGTON UNIVERSITY · PI STEWART, SHEILA A · 2018 to 2022
$2.5M
Leveraging the metastatic tumor stroma to limit breast cancer progressionR01CA282810 · NCI · WASHINGTON UNIVERSITY · PI Sheila A Stewart · 2024 to 2026
$1.4M
Senescent CAFs in Breast Cancer ProgressionR56AG088264 · NIA · WASHINGTON UNIVERSITY · PI STEWART, SHEILA A · 2024 to 2024
$389k
NCI NIH HHS P30 CA091842NCI NIH HHS R01 CA262555NCI NIH HHS R01 CA282810NCI NIH HHS R01 CA286615NIAMS NIH HHS P30 AR074992NIAMS NIH HHS T32 AR060719NIA NIH HHS R01 AG059244NIA NIH HHS R56 AG088264United States Department of Defense | Defense Intelligence Agency (DIA) MBC181712U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA282810U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R01AG059244U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging) R56AG088264
6 · The paper itself

Abstract

Chemotherapy-induced bone loss is a debilitating and common side effect of cancer treatment, though its underlying mechanisms remain poorly understood. Here, we show that, despite the systemic administration of chemotherapy, cellular senescence is restricted to bone marrow adipo-lineage cells specifically Cxcl12-abundant reticular (CAR) cells and bone marrow adipocytes (BMAds). Induction of senescence within these populations promotes RANK ligand (RANKL)-mediated osteoclastogenesis, leading to significant bone loss. Notably, we find that inhibition of the p38MAPK-MK2 pathway suppresses the senescence-associated secretory phenotype (SASP), including RANKL production abrogating bone loss. Furthermore, treatment with the senolytic combination dasatinib and quercetin (D + Q) selectively eliminates senescent CAR cells and BMAds, effectively preventing chemotherapy-induced bone loss. Given that nearly all chemotherapy treated patients experience bone loss and associated fracture risk, our findings offer a promising therapeutic avenue to preserve bone integrity and improve quality of life for cancer patients.

Indexed as

AdipocytesAntineoplastic AgentsBone ResorptionCellular SenescenceAnimalsBone Marrow CellsCell LineageChemokine CXCL12DasatinibFemaleHumansMaleMiceMice, Inbred C57BLOsteoclastsOsteogenesisAntineoplastic AgentsChemokine CXCL12Dasatinibp38 Mitogen-Activated Protein KinasesQuercetinRANK LigandSenotherapeutics

Identifiers

PMID41469373
PMCPMC12848019

What OpenQuestion holds

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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 OpenQuestion graph.