ArticleCell death & disease2013
Low FasL levels promote proliferation of human bone marrow-derived mesenchymal stem cells, higher levels inhibit their differentiation into adipocytes.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Expression changes in Fasl-deficient calvaria-derived osteoblasts: an RNA-seq analysis.Scientific data · 2025Article
- Proinflammatory cytokines sensitise mesenchymal stromal cells to apoptosis.Cell death discovery · 2025Article
- Exploring causal correlations between inflammatory response-related genes and osteoporosis: a Multi-Omics Mendelian Randomization Study.Archives of medical science : AMS · 2025Article
- Deep Learning-Predicted Dihydroartemisinin Rescues Osteoporosis by Maintaining Mesenchymal Stem Cell Stemness through Activating Histone 3 Lys 9 Acetylation.ACS central science · 2023Article
- Article
- Resistance of Human Liver Mesenchymal Stem Cells to FAS-Induced Cell Death.Current issues in molecular biology · 2022Article
- Treatment with Mesenchymal Stromal Cells Overexpressing Fas-Ligand Ameliorates Acute Graft-versus-Host Disease in Mice.International journal of molecular sciences · 2022Article
- FasL Is Required for Osseous Healing in Extraction Sockets in Mice.Frontiers in immunology · 2021Article
- miRNA‑15a‑5p facilitates the bone marrow stem cell apoptosis of femoral head necrosis through the Wnt/β‑catenin/PPARγ signaling pathway.Molecular medicine reports · 2019Article
- Fas-L promotes the stem cell potency of adipose-derived mesenchymal cells.Cell death & disease · 2018Article
- FasL Modulates Expression ofFrontiers in physiology · 2018Article
- TRAIL (TNF-related apoptosis-inducing ligand) inhibits human adipocyte differentiation via caspase-mediated downregulation of adipogenic transcription factors.Cell death & disease · 2016Article
- Local anesthetic bupivacaine induced ovarian and prostate cancer apoptotic cell death and underlying mechanisms in vitro.Scientific reports · 2016Article
- Critical role of PPARγ in myeloid-derived suppressor cell-stimulated cancer cell proliferation and metastasis.Oncotarget · 2016Article
- TNF-related apoptosis-inducing ligand promotes human preadipocyte proliferation via ERK1/2 activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Licochalcone A up-regulates of FasL in mesenchymal stem cells to strengthen bone formation and increase bone mass.Scientific reports · 2014Article
- Role of mesenchymal stem cells in cell life and their signaling.World journal of stem cells · 2014Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stem cells (MSCs) are multipotent progenitor cells that can differentiate into several cell types. Bone marrow (BM)-MSCs mainly differentiate into osteoblasts or adipocytes. MSC interactions with their microenvironment directly affect their self-renewal/differentiation program. Here, we show for the first time that Fas ligand (FasL), a well-explored proapoptotic cytokine, can promote proliferation of BM-derived MSCs in vitro and inhibits their differentiation into adipocytes. BM-MSCs treated with a low FasL dose (0.5 ng/ml) proliferated more rapidly than untreated cells without undergoing spontaneous differentiation or apoptosis, whereas higher doses (25 ng/ml) induced significant though not massive BM-MSC death, with surviving cells maintaining a stem cell phenotype. At the molecular level, 0.5 ng/ml FasL induced ERK1/2 phosphorylation and survivin upregulation, whereas 25 ng/ml FasL induced caspase activation. Importantly, 25 ng/ml FasL reversibly prevented BM-MSC differentiation into adipocytes by modulating peroxisome proliferator-activated receptor gamma (PPARγ) and FABP4/aP2 expression induced by adipogenic medium. All such effects were inhibited by anti-Fas neutralizing antibody. The in vitro data regarding adipogenesis were confirmed using Fas(lpr) mutant mice, where higher PPARγ and FABP4/aP2 mRNA and protein levels were documented in whole tibia. These data show for the first time that the FasL/Fas system can have a role in BM-MSC biology via regulation of both proliferation and adipogenesis, and may have clinical relevance because circulating Fas/FasL levels decline with age and several age-related conditions, including osteoporosis, are characterized by adipocyte accumulation in BM.
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Registered trials
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.