Mechanism of Wumen Gumibao Decoction Regulating Wnt/β-catenin and OPG/RANKL Pathways to Relieve Osteoporosis in Senescence Accelerated Mice
10.16466/j.issn1005-5509.2025.05.002
- VernacularTitle:吴门骨密葆方调控Wnt/β-catenin与OPG/RANKL通路改善快速骨老化小鼠骨质疏松症的机制
- Author:
Guodong ZHANG
1
;
Wanlin ZHANG
1
;
Yuwei LI
1
Author Information
1. 南京中医药大学附属苏州市中医医院 江苏,苏州 215009
- Publication Type:Journal Article
- Keywords:
Wumen Gumibao Decoction;
senile osteoporosis;
Wnt/β-catenin signaling pathway;
OPG/RANK/RANKL signaling pathway;
bone formation;
bone resorption;
senescence accelerated mouse prone 6;
mechanism research
- From:
Journal of Zhejiang Chinese Medical University
2025;49(5):536-545
- CountryChina
- Language:Chinese
-
Abstract:
[Objective]To investigate the mechanism of Wumen Gumibao Decoction in treating senile osteoporosis(SOP)of senescence accelerated mouse prone 6(SAMP6)mice.[Methods]SAM-resistant 1(SAMR1)mice was set as control group,SAMP6 mice were randomly divided into model group(SAMP6),Chinese medicine low dose group(SAMP6+Wumen Gumibao Decoction 7.5 g·kg-1)and Chinese medicine high dose group(SAMP6+Wumen Gumibao Decoction 15.0 g·kg-1),with 10 mice in each group.Mice in control group and model group were gavaged with equal volume of 0.9%sodium chloride solution,and the two groups of Chinese medicine were given Wumen Gumibao Decoction,once a day for 12 weeks.The changes of body mass were observed during the experiment.At the end of the experiment,hematoxylin-eosin(HE)staining was used to observe the pathological changes of the femur in mice.Micro computed tomography(Micro-CT)was used to observe the microstructure and parameters of the femur.The serum levels of calcium(Ca),phosphorus(P)was detected with biochemical method,and the serum levels of calcitonin(CT),procollagen type Ⅰ N-terminal propeptide(PⅠNP),bone γ-carboxyglutamic acid-containing protein(BGP),alkaline phosphatase(ALP),tartrate resistant acid phosphatase(TRACP),procollagen type Ⅰ C-terminal propeptide(PⅠCP),insulin-like growth factor-1(IGF-1),parathyroid hormone(PTH)were detected by enzyme-linked immunosorbent assay(ELISA).Immunohistochemical(IHC)staining was used to detect Wnt3α,phosphorylated-b-catenin(p-b-catenin),osteoprotegerin(OPG),receptor activator of nuclear factor-κB(RANK)and ligand of receptor activator of NF-κB(RANKL),secretory protein Dickkopf-1(DKK1)and glycogen synthase kinase 3b(GSK3b).[Results]Compared with control group,the cortical bone texture,direction and arrangement of bone cells in bone tissue of model group were disordered,and the trabecular structure was loose,showing a state of osteoporosis,bone microstructure parameters bone mineral density,bone volume/tissue volume ratio,trabecular number,trabecular thickness decreased significantly(P<0.05)and trabecular separation increased significantly(P<0.05).The serum levels of Ca,BGP,PⅠNP,CT and ALP were significantly decreased(P<0.05),and P,TRACP,PⅠCP and IGF-1 were significantly increased(P<0.05).In addition,the expression of Wnt3a as significantly down-regulated(P<0.05),and the expression of p-β-catenin,OPG,RANK,RANKL,DKK1 and GSK3β was significantly up-regulated(P<0.05).Compared with model group,Chinese medicine low and high dose groups can improve the pathological morphology of the femur to varying degrees,increase the number of bone trabeculae and reduced the fracture of bone trabeculae,and improved the related parameters of bone microstructure(P<0.05).The levels of serum Ca,CT,BGP,PⅠNP and ALP were increased(P<0.05),and the levels of P,TRACP,PⅠCP and IGF-1 were decreased(P<0.05),and PTH was increased(P<0.05).At the same time,it could up-regulate the expression of Wnt3α protein in the femur(P<0.05)and down-regulate the expression of p-β-catenin,OPG,RANK,RANKL,DKK1 and GSK3b protein(P<0.05).[Conclusion]Wumen Gumibao Decoction has the effect of significantly improving osteoporosis in SAMP6 mice,and its mechanism may be related to its regulation of Wnt/β-catenin and OPG/RANK/RANKL signaling pathways.
