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Published in: Journal of Orthopaedic Surgery and Research 1/2024

Open Access 01-12-2024 | Osteoporosis | Correspondence

Geniposide alleviates cholesterol-induced endoplasmic reticulum stress and apoptosis in osteoblasts by mediating the GLP-1R/ABCA1 pathway

Authors: Mingliang Zhong, Zhenyu Wu, Zhixi Chen, Longhuo Wu, Jianguo Zhou

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2024

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Abstract

Background

Cholesterol (CHO) is an essential component of the body. However, high CHO levels in the body can damage bone mass and promote osteoporosis. CHO accumulation can cause osteoblast apoptosis, which has a negative effect on bone formation. The pathogenesis of osteoporosis is a complicate process that includes oxidative stress, endoplasmic reticulum (ER) stress, and inflammation. Geniposide (GEN) is a natural compound with anti-osteoporotic effect. However, the roles of GEN in osteopathogenesis are still unclear. Our previous studies demonstrated that GEN could reduce the accumulation of CHO in osteoblasts and the activation of ER stress in osteoblasts. However, the molecular mechanism of GEN in inhibiting CHO-induced apoptosis in osteoblasts needs to be further investigated.

Methods

MC3T3-E1 cells were treated with osteogenic induction medium (OIM). Ethanol-solubilized cholesterol (100 µM) was used as a stimulator, and 10 µM and 25 µM geniposide was added for treatment. The alterations of protein expression were detected by western blot, and the cell apoptosis was analyzed by a flow cytometer.

Results

CHO promoted osteoblast apoptosis by activating ER stress in osteoblasts, while GEN alleviated the activation of ER stress and reduced osteoblast apoptosis by activating the GLP-1R/ABCA1 pathway. Inhibition of ABCA1 or GLP-1R could eliminate the protective activity of GEN against CHO-induced ER stress and osteoblast apoptosis.

Conclusion

GEN alleviated CHO-induced ER stress and apoptosis in osteoblasts by mediating the GLP-1R/ABCA1 pathway.
Literature
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go back to reference Hernlund E, Svedbom A, Ivergård M, Compston J, Cooper C, Stenmark J, et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 2013;8:136. https://doi.org/10.1007/s11657-013-0136-1.CrossRefPubMedPubMedCentral Hernlund E, Svedbom A, Ivergård M, Compston J, Cooper C, Stenmark J, et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 2013;8:136. https://​doi.​org/​10.​1007/​s11657-013-0136-1.CrossRefPubMedPubMedCentral
Metadata
Title
Geniposide alleviates cholesterol-induced endoplasmic reticulum stress and apoptosis in osteoblasts by mediating the GLP-1R/ABCA1 pathway
Authors
Mingliang Zhong
Zhenyu Wu
Zhixi Chen
Longhuo Wu
Jianguo Zhou
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2024
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-024-04665-4

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