Geniposide ameliorates cholesterol accumulation and promotes osteoblast differentiation by mediating the GLP-1R/AMPK/SREBP2 pathway DOI Creative Commons
Zhan Wang, Longhuo Wu, Shan Li

et al.

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: May 26, 2025

Glucocorticoid (GC)-induced OP (GIOP) is a systemic metabolic bone disease with high risk of fracture. Recently, lipid disorders, particularly hypercholesterolemia, have been correlated to the development OP. However, roles cholesterol accumulation in osteoblasts during GIOP pathological are still unclear. Our previous study shows that intracellular can suppress osteoblast differentiation and promote cell apoptosis. Geniposide (GEN), natural activator glucagon-like peptide-1 receptor (GLP-1R), exhibited protective activity against dexamethasone (DEX)-induced inhibition. Sterol regulatory element-binding protein 2 (SREBP2) regulates synthesis. Whether SREBP2 was involved DEX-induced unknown. rat models were duplicated. Micro-computed tomography (µCT) used scan proximal femurs, hematoxylin eosin (H&E) staining for histological examination. MC3T3-E1 cells study, ALP Alizarin Red S employed differentiation. pcDNA3.1-SREBP2 transfect cells. Western blotting assays expression. DEX enhanced expression mTOR promoted inhibition These could be rescued by GEN treatment. overexpression SREBP2, activation, AMPK GLP-1R block effects GEN. improved mediating GLP-1R/AMPK/mTOR/SREBP2 signaling.

Language: Английский

Geniposide ameliorates cholesterol accumulation and promotes osteoblast differentiation by mediating the GLP-1R/AMPK/SREBP2 pathway DOI Creative Commons
Zhan Wang, Longhuo Wu, Shan Li

et al.

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: May 26, 2025

Glucocorticoid (GC)-induced OP (GIOP) is a systemic metabolic bone disease with high risk of fracture. Recently, lipid disorders, particularly hypercholesterolemia, have been correlated to the development OP. However, roles cholesterol accumulation in osteoblasts during GIOP pathological are still unclear. Our previous study shows that intracellular can suppress osteoblast differentiation and promote cell apoptosis. Geniposide (GEN), natural activator glucagon-like peptide-1 receptor (GLP-1R), exhibited protective activity against dexamethasone (DEX)-induced inhibition. Sterol regulatory element-binding protein 2 (SREBP2) regulates synthesis. Whether SREBP2 was involved DEX-induced unknown. rat models were duplicated. Micro-computed tomography (µCT) used scan proximal femurs, hematoxylin eosin (H&E) staining for histological examination. MC3T3-E1 cells study, ALP Alizarin Red S employed differentiation. pcDNA3.1-SREBP2 transfect cells. Western blotting assays expression. DEX enhanced expression mTOR promoted inhibition These could be rescued by GEN treatment. overexpression SREBP2, activation, AMPK GLP-1R block effects GEN. improved mediating GLP-1R/AMPK/mTOR/SREBP2 signaling.

Language: Английский

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