ArticleThe Journal of clinical investigation2015
S-nitrosoglutathione reductase-dependent PPARγ denitrosylation participates in MSC-derived adipogenesis and osteogenesis.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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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.
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Who cites it
47 citing papers in PubMed, 81 citations in OpenAlex.
- Post-translational modification-regulating biomaterials for regeneration.Bioactive materials · 2026Review
- S-nitrosoglutathione reductase GSNOR drives age-related obesity by promoting adipose tissue whitening through de-nitrosation of Beclin-1.Nature communications · 2026Article
- Depletion of marrow adipo-CAR cells in mice enhances bone formation by activating bone morphogenetic protein receptor (BMPR) in pre-osteoblasts.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- S-Nitrosylation of NOTCH1 Regulates Mesenchymal Stem Cells Differentiation Into Hepatocyte-Like Cells by Inhibiting Notch Signalling Pathway.Journal of cellular and molecular medicine · 2024Article
- Cell-based therapy in the treatment of musculoskeletal diseases.Stem cells translational medicine · 2024Review
- Genetic Background Strongly Influences the Impact of Carrying the Thr92Ala-DIO2 Polymorphism in the Male Mouse.Endocrinology · 2024Article
- Fetal programming effect of rumen-protected methionine on primiparous Angus × Simmental offspring's performance and skeletal muscle gene expression.Journal of animal science · 2024Article
- Class III Alcohol Dehydrogenase Plays a Key Role in the Onset of Alcohol-Related/-Associated Liver Disease as an S-Nitrosoglutathione Reductase in Mice.International journal of molecular sciences · 2023Article
- The Potential Roles of Post-Translational Modifications of PPARγ in Treating Diabetes.Biomolecules · 2022Review
- TET enzymes regulate skeletal development through increasing chromatin accessibility of RUNX2 target genes.Nature communications · 2022Article
- Emerging role of m6A modification in osteogenesis of stem cells.Journal of bone and mineral metabolism · 2022Review
- Exosomal miR-155 from gastric cancer induces cancer-associated cachexia by suppressing adipogenesis and promoting brown adipose differentiationCancer biology & medicine · 2022Article
- GSNOR regulates ganoderic acid content in Ganoderma lucidum under heat stress through S-nitrosylation of catalase.Communications biology · 2022Article
- Correlation of ADIPOQ Gene Single Nucleotide Polymorphisms with Bone Strength Index in Middle-Aged and the Elderly of Guangxi Mulam Ethnic Group.International journal of environmental research and public health · 2021Article
- Alcohol consumption induces murine osteoporosis by downregulation of natural killer T-like cell activity.Immunity, inflammation and disease · 2021Article
- ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue.Cell reports · 2021Article
- Melatonin, Its Metabolites and Their Interference with Reactive Nitrogen Compounds.Molecules (Basel, Switzerland) · 2021Review
- Implications of Oxidative and Nitrosative Post-Translational Modifications in Therapeutic Strategies against Reperfusion Damage.Antioxidants (Basel, Switzerland) · 2021Review
- The effects of S-nitrosylation-induced PPARγ/SFRP5 pathway inhibition on the conversion of non-alcoholic fatty liver to non-alcoholic steatohepatitis.Annals of translational medicine · 2021Article
- S-nitrosoglutathione reductase (GSNOR) deficiency accelerates cardiomyocyte differentiation of induced pluripotent stem cells.The journal of cardiovascular aging · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
Bone marrow-derived mesenchymal stem cells (MSCs) are a common precursor of both adipocytes and osteoblasts. While it is appreciated that PPARγ regulates the balance between adipogenesis and osteogenesis, the roles of additional regulators of this process remain controversial. Here, we show that MSCs isolated from mice lacking S-nitrosoglutathione reductase, a denitrosylase that regulates protein S-nitrosylation, exhibited decreased adipogenesis and increased osteoblastogenesis compared with WT MSCs. Consistent with this cellular phenotype, S-nitrosoglutathione reductase-deficient mice were smaller, with reduced fat mass and increased bone formation that was accompanied by elevated bone resorption. WT and S-nitrosoglutathione reductase-deficient MSCs exhibited equivalent PPARγ expression; however, S-nitrosylation of PPARγ was elevated in S-nitrosoglutathione reductase-deficient MSCs, diminishing binding to its downstream target fatty acid-binding protein 4 (FABP4). We further identified Cys 139 of PPARγ as an S-nitrosylation site and demonstrated that S-nitrosylation of PPARγ inhibits its transcriptional activity, suggesting a feedback regulation of PPARγ transcriptional activity by NO-mediated S-nitrosylation. Together, these results reveal that S-nitrosoglutathione reductase-dependent modification of PPARγ alters the balance between adipocyte and osteoblast differentiation and provides checkpoint regulation of the lineage bifurcation of these 2 lineages. Moreover, these findings provide pathophysiological and therapeutic insights regarding MSC participation in adipogenesis and osteogenesis.
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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.