ArticleRedox biology2020
The Nrf2 activator RTA-408 attenuates osteoclastogenesis by inhibiting STING dependent NF-κb signaling.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.
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Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
- The DJ1-Nrf2-STING axis mediates the neuroprotective effects of Withaferin A in Parkinson's disease.Cell death and differentiation · 2021Pooled it
- Bone Marrow Macrophage STING Signaling is a Direct Nexus Linking Marrow Adipose Expansion to NADAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Heme Oxygenase-1 in Bone Remodeling: Molecular Mechanisms and Therapeutic Implications.Biomolecules · 2026Review
- Oxypaeoniflorin Ameliorates Titanium Particle-Stimulated Osteolysis by Targeting Nrf2 to Reprogram Mitochondrial Homeostasis in Osteoclasts.Journal of cellular and molecular medicine · 2026Article
- Spotlight on cGAS-STING: role in disease pathogenesis and therapeutic potential.Molecular biomedicine · 2026Review
- RTA-408 Enhances Radiosensitivity and Inhibited Tumor Progression via JNK Pathway in Glioblastoma.The Kaohsiung journal of medical sciences · 2026Article
- Cepharanthine hydrochloride alleviates herpesvirus encephalitis by inhibiting Nrf2 degradation.Virologica Sinica · 2026Article
- LncRNA-Gm5532 deficiency alleviates bone resorption by inhibiting mitochondrial respiration through iASPP/NRF2.Cell biology and toxicology · 2026Article
- Mechanistic and Therapeutic Insights into Nrf2-Mediated Redox Regulation in Periodontitis.Antioxidants (Basel, Switzerland) · 2026Review
- Oxidative stress and bone marrow adipocytes: Molecular mechanisms and possible implications.Journal of orthopaedic translation · 2026Review
- A novel circulating osteoimmunological signature for diagnosis: integrating CXCL2, FYN, galectin-3, and STING in postmenopausal osteoporosis.Frontiers in physiology · 2026Article
- Emerging targeted therapies for chronic obstructive pulmonary disease: from symptom control to precision medicine.Frontiers in pharmacology · 2026Review
- Modulation of Nrf2 and Mitochondrial Function: Pharmacological Implications.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Salvianolic Acid A Mitigates Osteoporotic Bone Loss by Repressing Reactive Oxygen Species via the Nrf2-HO-1 Pathway.Phytotherapy research : PTR · 2025Article
- The hidden driver of osteoporosis: mitochondria-dominated inflammation.Cell communication and signaling : CCS · 2025Review
- Nrf2/Nlrp3 signaling in aging BMSCs: Traf6 intervention as a novel approach to osteoporosis treatment.Redox biology · 2025Article
- Targeting Irgm1 to combat osteoporosis: suppressing ROS and restoring bone remodeling.Cell death & disease · 2025Article
- GLP-2-carrying exosomes alleviate osteoporosis by upregulating miR-378a-3p to inhibit osteoclastic differentiation and NF-κB-MAPK pathway.Journal of orthopaedic surgery and research · 2025Article
- Disruption of the KLHL37-N-Myc complex restores N-Myc degradation and arrests neuroblastoma growth in mouse models.The Journal of clinical investigation · 2025Article
- Targeting lipid raft-related stomatin to ameliorate osteoporosis in preclinical models.Nature communications · 2025Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The dysregulation of ROS production and osteoclastogenesis is involved in the progress of osteoporosis. To identify novel and effective targets to treat this disease, it is important to explore the underlying mechanisms. In our study, we firstly tested the effect of the Nrf2 activator RTA-408, a novel synthetic triterpenoid under clinical investigation for many diseases, on osteoclastogenesis. We found that it could inhibit osteoclast differentiation and bone resorption in a time- and dose-dependent manner. Further, RTA-408 enhanced the expression and activity of Nrf2 and significantly suppressed RANKL-induced reactive oxygen species (ROS) production. Nrf2 regulates the STING expression and STING induces the production of IFN-β. Here, we found that RTA-408 could suppress STING expression, but that it does not affect Ifnb1 expression. RANKL-induced degradation of IκBα and the nuclear translocation of P65 was suppressed by RTA-408. Although this compound was not found to influence STING-IFN-β signaling, it suppressed the RANKL-induced K63-ubiquitination of STING via inhibiting the interaction between STING and the E3 ubiquitin ligase TRAF6. Further, adenovirus-mediated STING overexpression rescued the suppressive effect of RTA-408 on NF-κB signaling and osteoclastogenesis. In vivo experiments showed that this compound could effectively attenuate ovariectomy (OVX)-induced bone loss in C57BL/6 mice by inhibiting osteoclastogenesis. Collectively, we show that RTA-408 inhibits NF-κB signaling by suppressing the recruitment of TRAF6 to STING, in addition to attenuating osteoclastogenesis and OVX-induced bone loss in vivo, suggesting that it could be a promising candidate for treating osteoporosis in the future.
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Registered trials
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