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Dendrobium offificinale polysaccharides prevents glucocorticoids-induced osteoporosis by destabilizing KEAP1-NRF2 interaction
Abstract
Glucocorticoid-induced osteoporosis (GIOP) represents the foremost cause of secondary osteoporosis and fragility fractures. Novel therapeutic strategies for GIOP are needed, with improved safety profiles and reduced costs compared to current options. Dendrobium officinale (D. officinale) is a traditional Chinese medicine that has been reported to have beneficial effects on bone metabolism. Here, we sought to investigate the impacts of D. officinale polysaccharides (DOP), the main active constituents of D. officinale, on GIOP in vivo models and dexamethasone (DEX)-treated osteoblast lineage cells. We found that low concentrations of DOP are relatively safe in vitro and in vivo, respectively. Importantly, we found that DOP treatment significantly inhibited DEX-induced osteoporosis in two in vivo models, zebrafish and mice, while boosting osteogenic differentiation of hBMSCs exposed to DEX. Futhermore, our data reveal that DOP elevates nuclear Nrf2 levels under DEX treatment, by suppressing of Nrf2 ubiquitination. Leveraging Keap1b knockout zebrafish and RNAi approach, we demonstrated that DOP disrupts the association of Nrf2/Keap1, resulting in the inhibition of Nrf2 ubiquitination. Taken together, these results illuminate that DOP stimulates osteogenesis in the presence of DEX by destabilizing the Nrf2/Keap1 interaction. These findings suggest that DOP may serve as a novel drug against osteoporosis caused by glucocorticoids.
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“Recent discoveries have highlighted the pivotal role of the Nrf2 signaling pathway, a central regulatory system of cellular antioxidant defense, in bone metabolism52,53.”
From Intelligence-responsive wettability switch coating on magnesium implants for treating osteoporotic fracture (2026) · cites this paper as [52]
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Metadata
- Authors
- Wang, Y., Jiang, Z., Deng, L., Zhang, G., Xu, X., Alonge, E., Zhang, H., & Guo, C.
- Affiliations
- Central South University (CN)
- Corresponding author
- Guo, Chaofeng
- Venue
- International Journal of Biological Macromolecules
- Publisher
- Elsevier BV
- Published
- 2023-12
- Volume
- 253
- Issue
- Pt 1
- Pages
- 126600
- ISSN
- 0141-8130 (ISSN-L)
- OpenAlex
- W4386248322
- Cited by
- 22
- References
- 37
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 4
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- International Journal of Biological Macromolecules (publishedVersion)
- PubMed (publishedVersion)
- Funders
- China Postdoctoral Science Foundation (2021 M703640)
- National Natural Science Foundation of China (kq2202372, 82170901, 82202048, 82270937)
- Natural Science Foundation of Hunan Province (2022JJ40822)
- Science and Technology Program of Hunan Province (2021RC2030)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Medicinal Plant Pharmacodynamics Research
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- Dendrobium officinale polysaccharide, glucocorticoid-induced osteoporosis, dexamethasone, Nrf2, Keap1, Nrf2 ubiquitination, osteogenic differentiation, bone marrow mesenchymal stem cells, traditional Chinese medicine, bone metabolism, zebrafish model
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Animals, Carrier Proteins, Glucocorticoids, Osteogenesis, Osteoporosis, Polysaccharides, Zebrafish, Zebrafish Proteins, Dendrobium, NF-E2-Related Factor 2, Mice
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