Geniposide suppressed OX-LDL-induced osteoblast apoptosis by regulating the NRF2/NF-κB signaling pathway
Yaosheng Xiao1,2, Shanshan Zhang3, Yongjun Ye2
1Medical College of Soochow University, Suzhou, 215123, China.
Background:
Osteoporosis (OP), due to microarchitectural alterations, is associated with decreased bone mass, declined strength, and increased fracture risk. Increased osteoblast apoptosis contributes to the progression of OP. Natural compounds from herbs provide a rich resource for drug screening. Our previous investigation showed that geniposide (GEN), an effective compound from Eucommia ulmoides, could protect against the pathological development of OP induced by cholesterol accumulation.
Methods:
The rat OP models were duplicated. Dual-energy X-ray absorptiometry, hematoxylin and eosin staining, and immunohistochemistry were used to evaluate bone changes. TUNEL/DAPI staining assays were used for cell apoptosis detection. Protein expression was determined by western blotting assays.
Results:
A high-fat diet promoted OP development in vivo, and OX-LDL stimulated osteoblast apoptosis in vitro. GEN exhibited protective activities against OX-LDL-induced osteoblast apoptosis by increasing the NRF2 pathway and decreasing the NF-κB pathway. PDTC, an NF-κB inhibitor, could further promote the biological functions of GEN. In contrast, ML385, an NRF2 inhibitor, might eliminate GEN's protection.
Conclusion:
GEN suppressed OX-LDL-induced osteoblast apoptosis by regulating the NRF2/NF-κB signaling pathway.
Insights
Geniposide (GEN) protects against osteoporosis by reducing osteoblast apoptosis. This natural compound regulates the NRF2/NF-κB pathway, offering a potential therapeutic strategy for bone loss.
Area of Science:
- Biochemistry
- Pharmacology
- Cell Biology
Background:
- Osteoporosis (OP) is characterized by decreased bone mass and increased fracture risk, with osteoblast apoptosis contributing to its progression.
- Natural compounds are explored for therapeutic potential; geniposide (GEN) from Eucommia ulmoides previously showed protective effects against OP induced by cholesterol accumulation.
Purpose of the Study:
- To investigate the protective effects of geniposide (GEN) against osteoblast apoptosis induced by oxidized low-density lipoprotein (OX-LDL).
- To elucidate the underlying molecular mechanisms involving the NRF2 and NF-κB signaling pathways.
Main Methods:
- Established rat osteoporosis (OP) models and in vitro osteoblast apoptosis models using OX-LDL.
- Evaluated bone changes using dual-energy X-ray absorptiometry and histological analyses.
- Assessed apoptosis via TUNEL/DAPI staining and determined protein expression using western blotting.
Main Results:
- A high-fat diet induced OP in vivo, while OX-LDL stimulated osteoblast apoptosis in vitro.
- GEN demonstrated protective effects by upregulating the NRF2 pathway and downregulating the NF-κB pathway.
- NF-κB inhibition (PDTC) enhanced GEN's effects, while NRF2 inhibition (ML385) abolished them.
Conclusions:
- Geniposide (GEN) effectively suppresses OX-LDL-induced osteoblast apoptosis.
- The protective mechanism involves the modulation of the NRF2/NF-κB signaling pathway.
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