PUBLICATION
Protosappanin B Activates the Wnt Pathway to Protect Against Glucocorticoid-Induced Osteoblast Inhibition and Enhance Bone Formation
- Authors
- Fan, J., Wang, Y., Yang, H., Huang, S., Ma, Y., Guo, J., Jia, Y., Zhang, Y., Fan, Y., Xiao, D., Zhang, J., Li, J., Dong, Y., Zhao, Y., Guo, M., Tang, Q., Li, S.S., Sun, T., Jin, X.
- ID
- ZDB-PUB-250223-6
- Date
- 2025
- Source
- Chemico-biological interactions : 111436111436 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Apoptosis/drug effects
- Osteogenesis*/drug effects
- Cell Differentiation/drug effects
- Mice
- Glucocorticoids*/pharmacology
- beta Catenin/metabolism
- Osteoblasts*/cytology
- Osteoblasts*/drug effects
- Osteoblasts*/metabolism
- Wnt Signaling Pathway*/drug effects
- Dexamethasone*/pharmacology
- Cell Line
- Animals
- Cell Proliferation/drug effects
- Zebrafish*
- Osteoporosis/chemically induced
- Osteoporosis/drug therapy
- Osteoporosis/metabolism
- Osteoporosis/pathology
- Osteoporosis/prevention & control
- PubMed
- 39986363 Full text @ Chem. Biol. Interact.
Citation
Fan, J., Wang, Y., Yang, H., Huang, S., Ma, Y., Guo, J., Jia, Y., Zhang, Y., Fan, Y., Xiao, D., Zhang, J., Li, J., Dong, Y., Zhao, Y., Guo, M., Tang, Q., Li, S.S., Sun, T., Jin, X. (2025) Protosappanin B Activates the Wnt Pathway to Protect Against Glucocorticoid-Induced Osteoblast Inhibition and Enhance Bone Formation. Chemico-biological interactions. :111436111436.
Abstract
Osteoporosis remains a major health challenge due to impaired osteoblast function and reduced bone formation, particularly in glucocorticoid-induced osteoporosis (GIOP). The Wnt/β-catenin signaling pathway plays a critical role in osteogenesis, making it a promising target for protective interventions against osteoporosis-related bone loss. In this study, virtual screening of a natural product library identified Protosappanin B (PB) as a potential Wnt pathway activator with high binding affinity for Wnt receptors. We investigated PB's protective effects on osteoblast function under glucocorticoid exposure using MC3T3-E1 cells treated with dexamethasone (DEX) and an in vivo zebrafish model of GIOP. PB significantly promoted osteoblast proliferation, facilitated cell cycle progression, and attenuated DEX-induced apoptosis in a dose-dependent manner. Additionally, PB enhanced osteoblast differentiation and mineralization, counteracting DEX's inhibitory effects on alkaline phosphatase (ALP) activity and calcium deposition. In zebrafish, PB mitigated DEX-induced skeletal defects, improving bone and craniofacial cartilage formation. Western blot analysis confirmed that PB restored β-catenin levels, activating the Wnt/β-catenin pathway. Notably, the osteogenic effects of PB were abolished by XAV939, a Wnt signaling inhibitor, further supporting its Wnt-dependent mechanism of action. These findings indicate that PB provides protective effects against glucocorticoid-induced osteoblast dysfunction and bone loss by modulating Wnt signaling. This study highlight the potential of PB as a natural agent for preventing GIOP-related bone deterioration and warrants further investigation into its clinical applicability.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping