ArticleCell death and differentiation2020
Dual targeting of SREBP2 and ERRα by carnosic acid suppresses RANKL-mediated osteoclastogenesis and prevents ovariectomy-induced bone loss.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- SREBP2 promotes macrophage alternative activation and allergic airway inflammation independent of cholesterol biosynthesis.Cell death & disease · 2026Article
- The interrelationship between prostate cancer and osteoporosis: new perspectives on shared molecular pathways and treatment strategies.International journal of surgery (London, England) · 2026Article
- Methyl carnosate, a carnosic acid derivative, attenuates osteoclastogenesis via modulation of RANKL-induced NF-κB activity.Frontiers in pharmacology · 2026Article
- Geniposide ameliorates cholesterol accumulation and promotes osteoblast differentiation by mediating the GLP-1R/AMPK/SREBP2 pathway.Journal of orthopaedic surgery and research · 2025Article
- Review
- Chiral Supramolecular Hydrogels Regulating Both Osteoblastogenesis and Osteoclastogenesis.Gels (Basel, Switzerland) · 2025Article
- RBBP6-Mediated ERRα Degradation Contributes to Mitochondrial Injury in Renal Tubular Cells in Diabetic Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- TIMP1 regulates ferroptosis in osteoblasts by inhibiting TFRC ubiquitination: an in vitro and in vivo study.Molecular medicine (Cambridge, Mass.) · 2024Article
- Targeted protein degradation: advances in drug discovery and clinical practice.Signal transduction and targeted therapy · 2024Review
- Ginsenoside Rg3 Restores Mitochondrial Cardiolipin Homeostasis via GRB2 to Prevent Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Circular RNAs in human diseases.MedComm · 2024Review
- Role of ubiquitination in the occurrence and development of osteoporosis (Review).International journal of molecular medicine · 2024Review
- Multiomics profiling reveals VDR as a central regulator of mesenchymal stem cell senescence with a known association with osteoporosis after high-fat diet exposure.International journal of oral science · 2024Article
- Bisphosphonate-incorporated coatings for orthopedic implants functionalization.Materials today. Bio · 2023Review
- HSP90β promotes osteoclastogenesis by dual-activation of cholesterol synthesis and NF-κB signaling.Cell death and differentiation · 2023Article
- RANKL Is Independently Associated with Increased Risks of Non-Alcoholic Fatty Liver Disease in Chinese Women with PCOS: A Cross-Sectional Study.Journal of clinical medicine · 2023Article
- Article
- A 3D-printed molybdenum-containing scaffold exerts dual pro-osteogenic and anti-osteoclastogenic effects to facilitate alveolar bone repair.International journal of oral science · 2022Article
- Estrogen-Related Receptor α: A Significant Regulator and Promising Target in Bone Homeostasis and Bone Metastasis.Molecules (Basel, Switzerland) · 2022Review
- Myeloid-derived growth factor (MYDGF) protects bone mass through inhibiting osteoclastogenesis and promoting osteoblast differentiation.EMBO reports · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoporosis develops because of impaired bone formation and/or excessive bone resorption. Several pharmacological treatment of osteoporosis has been developed; however, new treatments are still necessary. Cholesterol and estrogen receptor-related receptor alpha (ERRα) promote osteoclasts formation, survival, and cellular fusion and thus become high risk factors of osteoporosis. In this study, we identified that carnosic acid (CA) suppressed bone loss by dual-targeting of sterol regulatory element-binding protein 2 (SREBP2, a major regulator that regulates cholesterol synthesis) and ERRα. Mechanistically, CA reduced nuclear localization of mature SREBP2 and suppressed de novo biogenesis of cholesterol. CA subsequently decreased the interaction between ERRα and peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1β), resulting in decreased the transcription activity of ERRα and its target genes expression. Meanwhile, CA directly bound to the ligand-binding domain of ERRα and significantly promoted its ubiquitination and proteasomal degradation. Subsequently, STUB1 was identified as the E3 ligase of ERRα. The lysine residues (K51 and K68) are essential for ubiquitination and proteasomal degradation of ERRα by CA. In conclusion, CA dually targets SREBP2 and ERRα, thus inhibits the RANKL-induced osteoclast formation and improves OVX-induced bone loss. CA may serve as a lead compound for pharmacological control of osteoporosis.
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