Mechanism of icariin in promoting osteogenic differentiation of BMSCs and improving bone metabolism disorders through caveolin-1/Hippo signaling pathway.
10.19540/j.cnki.cjcmm.20240909.102
- Author:
Yi-Dan HAN
1
;
Hai-Feng ZHANG
1
;
Yun-Teng XU
1
;
Yu-Huan ZHONG
1
;
Xiao-Ning WANG
1
;
Yun YU
1
;
Yuan-Li YAN
1
;
Shan-Shan WANG
1
;
Xi-Hai LI
2
Author Information
1. College of Integrative Medicine, Fujian University of Traditional Chinese Medicine Fuzhou 350122, China.
2. Science and Technology Department, Fujian University of Traditional Chinese Medicine Fuzhou 350122, China Fujian Key Laboratory of Integrative Medicine on Geriatrics Fuzhou 350122, China.
- Publication Type:Journal Article
- Keywords:
Hippo/TAZ;
bone mesenchymal stem cells;
caveolin-1;
icariin;
osteogenic differentiation;
postmenopausal osteoporosis
- MeSH:
Animals;
Mesenchymal Stem Cells/metabolism*;
Caveolin 1/genetics*;
Osteogenesis/drug effects*;
Rats, Sprague-Dawley;
Rats;
Cell Differentiation/drug effects*;
Female;
Signal Transduction/drug effects*;
Flavonoids/administration & dosage*;
Protein Serine-Threonine Kinases/genetics*;
Drugs, Chinese Herbal/pharmacology*;
Cells, Cultured;
Humans
- From:
China Journal of Chinese Materia Medica
2025;50(3):600-608
- CountryChina
- Language:Chinese
-
Abstract:
Guided by the theory of "the kidney storing essence, governing the bones, and producing marrow", this study explored the mechanism of icariin(ICA) in regulating the osteogenic differentiation of rat bone mesenchymal stem cells(BMSCs) through caveolin-1(Cav1) via in vitro and in vivo experiments, aiming to provide a theoretical basis for the prevention and treatment of postmenopausal osteoporosis with traditional Chinese medicine(TCM). Primary cells were obtained from 4-week-old female SD rats using the whole bone marrow adherent method. Flow cytometry was used to detect the expression of surface markers CD29, CD90, CD11b, and CD45. The potential for osteogenic and adipogenic differentiation was assessed. The effect of ICA on cell viability was determined using the CCK-8 assay, and the impact of ICA on the formation of mineralized nodules was verified by alizarin red staining. A stable Cav1-silenced cell line was constructed using lentivirus. The effect of Cav1 silencing on osteogenic differentiation was observed via alizarin red staining. Western blot analysis was conducted to detect the expression of Cav1, Hippo/TAZ, and osteogenic markers such as Runt-related transcription factor 2(RUNX2) and alkaline phosphatase(ALP). The results showed that primary cells were successfully obtained using the whole bone marrow adherent method, positively expressing surface markers of rat BMSCs and possessing the potential for both osteogenic and adipogenic differentiation. The CCK-8 assay and alizarin red staining results indicated that 1×10~(-7) mol·L~(-1) was the optimal concentration of ICA for intervention in this experiment(P<0.05). During osteogenic induction, ICA inhibited Cav1 expression(P<0.05) while promoting TAZ expression(P<0.05). Alizarin red staining demonstrated that Cav1 silencing significantly promoted the osteogenic differentiation of BMSCs. After ICA intervention, TAZ expression was activated, and the expression of osteogenic markers ALP and RUNX2 was increased. In conclusion, Cav1 silencing significantly promotes the osteogenic differentiation of BMSCs, and ICA promotes this differentiation by inhibiting Cav1 and regulating the Hippo/TAZ signaling pathway.