ArticleStem cells (Dayton, Ohio)2012
NADPH oxidase 2 regulates bone marrow microenvironment following hindlimb ischemia: role in reparative mobilization of progenitor cells.
Article in Stem cells (Dayton, Ohio), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Myeloid DRP1 Sulfenylation Drives Reparative Macrophage Polarization and Neovascularization in Ischemic Muscle.Antioxidants (Basel, Switzerland) · 2026Article
- Diet-induced obesity induces oxidative stress and enhances H3K4me3 levels, driving nonresolving inflammation and myelopoiesis in hematopoietic stem and progenitor cells.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Defect in Migration of HSPCs in Nox-2 Deficient Mice Explained by Impaired Activation of Nlrp3 Inflammasome and Impaired Formation of Membrane Lipid Rafts.Stem cell reviews and reports · 2025Article
- Hematopoietic Stem Cells in Wound Healing Response.Advances in wound care · 2022Article
- Ischemic-Trained Monocytes Improve Arteriogenesis in a Mouse Model of Hindlimb Ischemia.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- Effect of erythropoietin administration on expression of mRNA brain-derived Neutrophic factor, levels of stromal cell-derived Factor-1, and neuron specific enolase in brain injury modelAnnals of medicine and surgery (2012) · 2021Article
- NADPH Oxidases: Redox Regulators of Stem Cell Fate and Function.Antioxidants (Basel, Switzerland) · 2021Review
- Pleiotropic and Potentially Beneficial Effects of Reactive Oxygen Species on the Intracellular Signaling Pathways in Endothelial Cells.Antioxidants (Basel, Switzerland) · 2021Review
- Modification of Cardiac Progenitor Cell-Derived Exosomes by miR-322 Provides Protection against Myocardial Infarction through Nox2-Dependent Angiogenesis.Antioxidants (Basel, Switzerland) · 2019Article
- Global Identification of HIF-1α Target Genes in Benzene Poisoning Mouse Bone Marrow Cells.International journal of environmental research and public health · 2018Article
- Oxidant Signaling Mediated by Nox2 in Neutrophils Promotes Regenerative Myelopoiesis and Tissue Recovery following Ischemic Damage.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- NADPH Oxidases, Angiogenesis, and Peripheral Artery Disease.Antioxidants (Basel, Switzerland) · 2017Review
- Nox2 contributes to the arterial endothelial specification of mouse induced pluripotent stem cells by upregulating Notch signaling.Scientific reports · 2016Article
- Copper Transport Protein Antioxidant-1 Promotes Inflammatory Neovascularization via Chaperone and Transcription Factor Function.Scientific reports · 2015Article
- Impaired compensation to femoral artery ligation in diet-induced obese mice is primarily mediated via suppression of collateral growth by Nox2 and p47phox.American journal of physiology. Heart and circulatory physiology · 2015Article
- NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress.Antioxidants & redox signaling · 2015Review
- Mechanosignaling in the vasculature: emerging concepts in sensing, transduction and physiological responses.American journal of physiology. Heart and circulatory physiology · 2015Review
- Critical Roles of Reactive Oxygen Species in Age-Related Impairment in Ischemia-Induced Neovascularization by Regulating Stem and Progenitor Cell Function.Oxidative medicine and cellular longevity · 2015Review
- Reactive oxygen species regulate hematopoietic stem cell self-renewal, migration and development, as well as their bone marrow microenvironment.Antioxidants & redox signaling · 2014Review
- Redox and metabolic regulation of stem/progenitor cells and their niche.Antioxidants & redox signaling · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Bone marrow (BM) microenvironment, which is regulated by hypoxia and proteolytic enzymes, is crucial for stem/progenitor cell function and mobilization involved in postnatal neovascularization. We demonstrated that NADPH oxidase 2 (Nox2)-derived reactive oxygen species (ROS) are involved in postischemic mobilization of BM cells and revascularization. However, role of Nox2 in regulating BM microenvironment in response to ischemic injury remains unknown. Here, we show that hindlimb ischemia of mice increases ROS production in both the endosteal and central region of BM tissue in situ, which is almost completely abolished in Nox2 knockout (KO) mice. This Nox2-dependent ROS production is mainly derived from Gr-1(+) myeloid cells in BM. In vivo injection of hypoxyprobe reveals that endosteum at the BM is hypoxic with high expression of hypoxia-inducible factor-1α in basal state. Following hindlimb ischemia, hypoxic areas and HIF-1α expression are expanded throughout the BM, which is inhibited in Nox2 KO mice. This ischemia-induced alteration of Nox2-dependent BM microenvironment is associated with an increase in vascular endothelial growth factor expression and Akt phosphorylation in BM tissue, thereby promoting Lin(-) progenitor cell survival and expansion, leading to their mobilization from BM. Furthermore, hindlimb ischemia increases proteolytic enzymes membrane type 1-matrix metalloproteinase (MMP) expression and MMP-9 activity in BM, which is inhibited in Nox2 KO mice. In summary, Nox2-dependent increase in ROS plays a critical role in regulating hypoxia expansion and proteolytic activities in BM microenvironment in response to tissue ischemia. This in turn promotes progenitor cell expansion and reparative mobilization from BM, leading to postischemic neovascularization and tissue repair.
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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.