A Modified Formula of Xian Fang Huo Ming Yin Promotes Osteoblast Differentiation through Wnt/β-catenin Signaling Pathway to Attenuate Medication-related Osteonecrosis of the Jaw in Mice
10.13241/j.cnki.pmb.2025.16.001
- VernacularTitle:仙方活命饮化裁方通过Wnt/β-catenin信号通路促进小鼠成骨细胞分化减轻药物相关性颌骨坏死
- Author:
Chang-ce WEI
1
;
Yan-jun PAN
;
Chun-juan ZHANG
;
Nai-wen ZHANG
;
Miao JIANG
;
Tian-gong LU
Author Information
1. 北京中医药大学生命科学学院 北京 100029
- Publication Type:Journal Article
- Keywords:
Medication-related osteonecrosis of the jaw;
Xian Fang Huo Ming Yin;
Network pharmacology;
Molecular docking
- From:
Progress in Modern Biomedicine
2025;25(16):2561-2576
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the potential mechanism of action of Xian Fang Huo Ming Yin modified formula(XFHMY)in the treatment of medication-related osteonecrosis of the jaw(MRONJ)through bioinformatics analysis and in vitro and in vivo experiments.Methods:Firstly,the efficacy of XFHMY was evaluated by establishing a mice model of MRONJ induced by zoledronic acid(ZOL);Subsequently,the potential molecular mechanism of XFHMY in the treatment of MRONJ was predicted by using network pharmacology;Lastly,the network pharmacology prediction results were collectively validated through MC3T3-E1 cell proliferation and differentiation experiments,Western blot analysis,and immunohistochemical staining of mouse maxillary bone tissue.Results:Animal experiments showed that,compared to the model group,the XFHMY group exhibited significantly improved wound healing in the tooth extraction socket(P＜0.001),a significant reduction in bone volume fraction and empty lacunae rate in the maxilla(P＜0.0001,P＜0.001),and a significant increase in trabecular separation and osteoclast number(P＜0.01,P＜0.05).Network pharmacology analysis identified 59 common targets,with both GO and KEGG analyses indicating the Wnt/β-catenin signaling pathway as a crucial mechanism for XFHMY in treating MRONJ.Ten key active components,including quercetin,luteolin,and fisetin,were screened,and these compounds demonstrated strong binding affinity with CTNNB1,a core target of this pathway.In vitro experiments revealed that XFHMY(0.25,0.5,1,2,4 mg/mL)promoted MC3T3-E1 cell proliferation(P＜0.0001)and activated the Wnt/β-catenin pathway by upregulating β-catenin and Runx2 protein expression,thereby reversing ZOL-induced inhibition of MC3T3-E1 cell proliferation and differentiation while enhancing both processes.Immunohistochemical analysis of mouse maxillae showed that,compared to the model group,the XFHMY group had significantly increased β-catenin and Runx2 protein expression(P＜0.05,P＜0.01),consistent with the in vitro findings.Conclusion:XFHMY promotes the proliferation and differentiation of osteoblasts through activating the Wnt/β-catenin signaling pathway,which in turn attenuates MRONJ.The novel pharmacological mechanism proposed in this study provides a theoretical basis for the clinical application of XFHMY.
