ArticleThe Journal of biological chemistry2013
The Keap1/Nrf2 protein axis plays a role in osteoclast differentiation by regulating intracellular reactive oxygen species signaling.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 195 citations in OpenAlex.
- WDR23 prevents bone loss by promoting autophagic degradation of TRAF6 in osteoclastogenesis.Bone research · 2026Article
- Molecular Hydrogen and the Uremic Skeleton: A Critical Review and Turnover-State-Dependent Redox Hypothesis in CKD-MBD.Antioxidants (Basel, Switzerland) · 2026Review
- Neutrophil extracellular traps in osteoporosis: mechanistic links to bone remodeling imbalance and therapeutic perspectives.Molecular biology reports · 2026Review
- Mechanistic and Therapeutic Insights into Nrf2-Mediated Redox Regulation in Periodontitis.Antioxidants (Basel, Switzerland) · 2026Review
- Si Inhibited Osteoclastogenesis: The Role of Fe and the Fenton Reaction.Advanced healthcare materials · 2025Article
- Integration of transcriptomics and metabolomics reveals the mechanism of Lycium barbarum polysaccharides inhibited MCF-7 cell proliferation.Scientific reports · 2025Article
- Nrf2 signaling in bone health: unlocking new avenues for osteoporosis management.Inflammopharmacology · 2025Review
- Nrf2 signaling pathway: focus on oxidative stress in osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2025Review
- Antioxidative fullerol prevents bone loss due to its anti-osteoclastogenic and pro-osteogenic activities.Nanomedicine : nanotechnology, biology, and medicine · 2025Article
- Effect of natural compounds on NRF2/KEAP1 signaling in periodontitis: a potential use to prevent age-related disorders.Molecular biology reports · 2025Review
- Post-COVID Condition and Neuroinflammation: Possible Management with Antioxidants.Antioxidants (Basel, Switzerland) · 2025Review
- Divergent Requirements for Glutathione Biosynthesis During Osteoclast Differentiation In Vitro and In Vivo.Antioxidants (Basel, Switzerland) · 2025Article
- Hyperbaric Oxygen Therapy for the Treatment of Bone-Related Diseases.International journal of molecular sciences · 2025Review
- Cycloastragenol in inflammation-related diseases: mechanisms, pharmacokinetics, and translational prospects.Frontiers in pharmacology · 2025Review
- The impact of IgSF11-PKM2 pathway on gene expression in osteoclasts.microPublication biology · 2025Article
- Article
- Transcriptomic Characterization Reveals Mitochondrial Involvement in Nrf2/Keap1-Mediated Osteoclastogenesis.Antioxidants (Basel, Switzerland) · 2024Article
- Sulforaphane inhibits multiple myeloma cell-induced osteoclast differentiation and macrophage proliferation by elevating ferroportin1.Cancer chemotherapy and pharmacology · 2024Article
- Nrf2 depletion enhanced curcumin therapy effect in gastric cancer by inducing the excessive accumulation of ROS.Scientific reports · 2024Article
- Improvement of antioxidant capability by dietary N-acetyl cysteine supplementation alleviates bone loss induced by chronic heat stress in finisher broilers.Journal of animal science and biotechnology · 2024Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reactive oxygen species (ROS) act as intracellular signaling molecules in the regulation of receptor activator of nuclear factor-κB ligand (RANKL)-dependent osteoclast differentiation, but they also have cytotoxic effects that include peroxidation of lipids and oxidative damage to proteins and DNA. Cellular protective mechanisms against oxidative stress include transcriptional control of cytoprotective enzymes by the transcription factor, nuclear factor E2-related factor 2 (Nrf2). This study investigated the relationship between Nrf2 and osteoclastogenesis. Stimulation of osteoclast precursors (mouse primary peritoneal macrophages and RAW 264.7 cells) with RANKL resulted in the up-regulation of kelch-like ECH-associated protein 1 (Keap1), a negative regulator of Nrf2. It also decreased the Nrf2/Keap1 ratio, and it down-regulated cytoprotective enzymes (heme oxygenase-1, γ-glutamylcysteine synthetase, and glucose-6-phosphate dehydrogenase). Nrf2 overexpression up-regulated the expression of cytoprotective enzymes, decreased ROS levels, decreased the number of tartrate-resistant acid phosphatase-positive multinucleated cells, reduced marker genes for osteoclast differentiation, and attenuated bone destruction in both in vitro and in vivo models. Overexpression of Keap1 or RNAi knockdown of Nrf2 exerted the opposite actions. In addition, in vivo local Nrf2 overexpression attenuated lipopolysaccharide-mediated RANKL-dependent cranial bone destruction in vivo. This is the first study to show that the Keap1/Nrf2 axis regulates RANKL-dependent osteoclastogenesis through modulation of intracellular ROS signaling via expression of cytoprotective enzymes. This raises the exciting possibility that the Keap1-Nrf2 axis may be a therapeutic target for the treatment of bone destructive disease.
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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.