ArticleThe Biochemical journal2011
Reactive oxygen species derived from Nox4 mediate BMP2 gene transcription and osteoblast differentiation.
Article in The Biochemical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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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.
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Who cites it
79 citing papers in PubMed, 143 citations in OpenAlex.
- Emerging potential of engineered nanozymes in periodontitis treatment: from monotherapy to hierarchical therapy.Journal of nanobiotechnology · 2026Review
- Gamma-Oryzanol Attenuates Aortic Valve Interstitial Cell Calcification via Suppression of BMP2-SMAD and MAPK Signaling Pathways.Biomolecules · 2026Article
- BMP-Dependent Modulation of ROS Generation and Scavenging Controls Interdigital Cell Death.Development, growth & differentiation · 2026Article
- ROS-scavenging nanomaterials as emerging tools for bone tissue regeneration: A comprehensive review of recent progress.Acta pharmaceutica Sinica. B · 2025Review
- Zingerone treats postmenopausal osteoporosis via increased ferroptosis sensitivity by p53-mediated regulation of SAT1 and GPX4 expression.Communications biology · 2025Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Metallothionein 3 promotes osteoclast differentiation and survival by regulating the intracellular ZnCell death discovery · 2023Article
- Article
- Astaxanthin as a Potent Antioxidant for Promoting Bone Health: An Up-to-Date Review.Antioxidants (Basel, Switzerland) · 2023Review
- Remodeling of the osteoimmune microenvironment after biomaterials implantation in murine tibia: Single-cell transcriptome analysis.Bioactive materials · 2023Article
- Exosome-mediated crosstalk between epithelial cells amplifies the cell injury cascade in CaOx stone formation.Journal of biological engineering · 2023Article
- Article
- Impact of exogenous hydrogen peroxide on osteogenic differentiation of broiler chicken compact bones derived mesenchymal stem cells.Frontiers in physiology · 2023Article
- Cell energy metabolism and bone formation.Bone reports · 2022Article
- The Effects of the Exposure of Musculoskeletal Tissue to Extracorporeal Shock Waves.Biomedicines · 2022Review
- Effect of Cold Atmospheric Plasma (CAP) on Osteogenic Differentiation Potential of Human Osteoblasts.International journal of molecular sciences · 2022Article
- Bioinformatics-Guided Analysis Uncovers AOX1 as an Osteogenic Differentiation-Relevant Gene of Human Mesenchymal Stem Cells.Frontiers in molecular biosciences · 2022Article
- Understanding Reactive Oxygen Species in Bone Regeneration: A Glance at Potential Therapeutics and Bioengineering Applications.Frontiers in bioengineering and biotechnology · 2022Review
- Oxidative Stress Induced Osteocyte Apoptosis in Steroid-Induced Femoral Head Necrosis.Orthopaedic surgery · 2021Article
- [Role of p22phox and NOX5 in autophagy and apoptosis of osteoblasts induced by hypoxia].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2021Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
BMP-2 (bone morphogenetic protein-2) promotes differentiation of osteoblast precursor cells to mature osteoblasts that form healthy bone. In the present study, we demonstrate a novel mechanism of BMP-2-induced osteoblast differentiation. The antioxidant NAC (N-acetyl-L-cysteine) and the flavoprotein enzyme NAD(P)H oxidase inhibitor DPI (diphenyleneiodonium) prevented BMP-2-stimulated alkaline phosphatase expression and mineralized bone nodule formation in mouse 2T3 pre-osteoblasts. BMP-2 elicited a rapid generation of ROS (reactive oxygen species) concomitant with increased activation of NAD(P)H oxidase. NAC and DPI inhibited BMP-2-induced ROS production and NAD(P)H oxidase activity respectively. NAD(P)H oxidases display structurally similar catalytic subunits (Nox1-5) with differential expression in various cells. We demonstrate that 2T3 pre-osteoblasts predominantly express the Nox4 isotype of NAD(P)H oxidase. To extend this finding, we tested the functional effects of Nox4. Adenovirus-mediated expression of dominant-negative Nox4 inhibited BMP-2-induced alkaline phosphatase expression. BMP-2 promotes expression of BMP-2 for maintenance of the osteoblast phenotype. NAC and DPI significantly blocked BMP-2-stimulated expression of BMP2 mRNA and protein due to a decrease in BMP2 gene transcription. Dominant-negative Nox4 also mimicked this effect of NAC and DPI. Our results provide the first evidence for a new signalling pathway linking BMP-2-stimulated Nox4-derived physiological ROS to BMP-2 expression and osteoblast differentiation.
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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 Socratic graph.