Mechanism of Cistanche phenylethanoid glycosides in treating osteoporosis by regulating osteogenic differentiation via SIRT2-C/EBPβ-AREG axis
10.12007/j.issn.0258-4646.2025.11.009
- VernacularTitle:肉苁蓉苯乙醇苷通过SIRT2-C/EBPβ-AREG轴调节成骨分化治疗骨质疏松症
- Author:
Yue ZHANG
1
;
Lizi YE
;
Leiming LUO
;
Yuanhui WANG
;
Zhi WANG
;
Zhong LI
Author Information
1. 西南医科大学附属医院小儿外科,四川泸州 646000;西南医科大学附属医院骨与关节外科,四川泸州 646000
- Publication Type:Journal Article
- Keywords:
Cistanche phenylethanoid glycosides;
SIRT2-C/EBPβ-AREG axis;
osteogenic differentiation;
osteoporosis
- From:
Journal of China Medical University
2025;54(11):1011-1016,1022
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism of Cistanche phenylethanoid glycosides(CPhGs)in treating osteoporosis by regu-lating osteogenic differentiation via SIRT2-C/EBPβ-AREG axis.Methods An osteoporosis mouse model was established using ova-riectomy.Trabecular number/thickness,bone formation rate,and tissue morphology were evaluated using micro-computed tomography,calcein double labeling,and hematoxylin and eosin staining,respectively.SIRT2,C/EBPβ,AREG,proteins related to the SIRT2-C/EBPβ-AREG axis,were analyzed by Western blotting and co-immunoprecipitation.The mRNA expression of osteogenic differentiation marker genes OCN,OPN,RUNX2,C/EBPβ,and AREG were detected by real-time quantitative PCR.Results CPhGs intervention significantly improved the trabecular microarchitecture and promoted bone formation in mice undergoing ovariectomy,and the mechanism involved the activation of SIRT2-mediated deacetylation of C/EBPβ,which in turn upregulated AREG expression.Cell experiments confirmed that CPhGs significantly increased the activity of alkaline phosphatase and the expression of osteogenic genes such as OCN,OPN,and RUNX2 in MC3T3-E1 cells by enhancing the interaction between SIRT2 and C/EBPβ.Notably,this effect could be reversed by SIRT2 knockdown.Conclusion CPhGs regulate the osteogenic differentiation process through the SIRT2-C/EBPβ-AREG axis,providing a new molecular target and theoretical basis for the treatment of osteoporosis with the active ingredients of traditional Chinese medicine.
