Mechanism of Liuwei dihuang pill promoting tendon-bone healing by regulating cell crosstalk through Wnt/β-catenin pathway
- VernacularTitle:六味地黄丸通过Wnt/β-连环蛋白通路调控细胞交互促进腱骨愈合的机制
- Author:
Peng ZHANG
1
;
Honglüe TAN
2
;
Xiaotao SHI
2
;
Xiao WANG
2
;
Peizhao WANG
2
;
Yanhao YUAN
2
;
Renkun ZHAO
3
;
Guorui CAO
2
Author Information
1. Graduate School，Hunan University of Chinese Medicine，Changsha 410208，China;Knee Surgery Center，Luoyang Orthopedic-Traumatological Hospital of Henan Province （Henan Provincial Orthopedic Hospital），Henan Luoyang 471002，China
2. Knee Surgery Center，Luoyang Orthopedic-Traumatological Hospital of Henan Province （Henan Provincial Orthopedic Hospital），Henan Luoyang 471002，China
3. The Second Department of Spine，Wangjing Hospital of China Academy of Chinese Medical Sciences，Beijing 100102，China
- Publication Type:Journal Article
- Keywords:
Liuwei dihuang pill;
bone marrow mesenchymal stem cells;
Wnt/β-catenin pathway;
tendon-bone healing;
macrophage polarization
- From:
China Pharmacy
2026;37(13):1722-1727
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the mecha nism by which Liuwei dihuang pill promotes tendon-bone healing by regulating the interaction between bone marrow mesenchymal stem cells （BMSCs） and macrophages through Wnt/ β -catenin pathway. METHODS BMSCs were co-cultured with macrophages at a ratio of 1∶4 and divided into control group， 10% drug-containing serum group， 20% drug-containing serum group， Wnt/ β -catenin pathway inhibitor Dickkopf-related protein 1 （DKK-1） group， and 20% drug-containing serum+DKK-1 group. After 48 hours of cell co-culture and 14 days of osteogenic induction， the CD86 and CD206 positive cell rates in macrophages， the proportion of calcium nodule positive staining area in BMSCs， the levels of osteocalcin （OCN） and oncostatin M （OSM） and alkaline phosphatase （ALP） activity in cell supernatant， as well as the mRNA and protein expression levels of OCN， Runt-related transcription factor 2 （RUNX2）， OSM， low-density lipoprotein receptor-related protein 5 （LRP5）， β -catenin in cells were detected. Pearson correlation analysis was performed to assess the correlation between LRP5 and β -catenin protein expression with OCN， RUNX2， OSM protein expression， and CD206 positive cell rate， respectively. RESULTS Compared with the control group， the CD86 positive cell rates in the 10% drug-containing serum group and the 20% drug-containing serum group were significantly reduced， while the CD206 positive cell rate， proportion of calcium nodule positive staining area， OCN level， OSM level， ALP activity， and mRNA and protein expression levels of OCN， RUNX2， OSM， LRP5， β -catenin were significantly increased （ P ＜0.05）. Compared with the 20% drug-containing serum group， the changes in the above indicators in the 20% drug-containing serum+DKK-1 group were significantly reversed （ P ＜0.05）. The protein expression of LRP5 and β -catenin was positively correlated with the pro tein expression of OCN， RUNX2， OSM， and CD206 positive cell rate. CONCLUSIONS Liuwei dihuang pill can activate the Wnt/ β -catenin pathway， induce M2 polarization of macrophages and secretion of OSM， promote osteogenic differentiation and matrix mineralization of BMSCs， and synergistically promote tendon-bone healing.
