Effect of Wenjing Tongluo Decoction on VEGF/VEGFR2/ERK1/2 Signaling Pathway in Mice with Knee Osteoarthritis / 中国实验方剂学杂志

ABSTRACT

Objective:To investigate the possible mechanism of Wenjing Tongluo decoction （WTD） in alleviating articular cartilage defect in knee osteoarthritis （KOA） and delaying joint degeneration. Method:The KOA model was established by anterior cruciate ligament transection （ACLT）. Mice were classified into sham-operated group， model group， WTD high-dose and low-dose groups， and positive control group. Four weeks after modeling， WTD groups and the positive control group were given WTD （80， 20 g·kg^-1） and glucosamine sulfate capsules （0.29 g·kg^-1）， respectively， and the sham-operated group and model group received normal saline of the equivalent volume. After continuous intervention for 4 weeks， hemoxylin-eosin （HE） staining was used to observe the morphological changes of cartilage and Mankin scoring system was employed to score the knee cartilage. Western blot was combined with Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） to detect the protein and mRNA levels of vascular endothelial growth factor <italic>α</italic> （VEGFA）， vascular endothelial growth factor receptor 2 （VEGFR2）， extracellular signal-related kinase 1/2 （ERK1/2） and a disintegrin and metalloproteinase with thrombospondin motifs 4 （ADAMTS4）. Result:The Mankin score in the model group increased as compared with that in the sham-operated group （<italic>P</italic><0.01）. Compared with the model group， administration groups demonstrated alleviated articular cartilage defect and low Mankin score （<italic>P</italic><0.01）， but there was no statistical significance in Mankin score between the WTD groups and positive control group. The protein and mRNA levels of VEGFA， VEGFR2， ERK1/2， and ADAMTS4 in the model group were significantly higher than those in the sham-operated group （<italic>P</italic><0.01）. The protein expression of VEGFA and ERK1/2 was inhibited in each administration group as compared with that in the model group （<italic>P</italic><0.01）， and the inhibition in the positive control group was stronger than that in the WTD low-dose group （<italic>P</italic><0.05） but weaker than that in the WTD high-dose group （<italic>P</italic><0.01）. Glucosamine Sulfate capsules suppressed the expression of VEGFR2 and ADAMTS4 to the extent the same with low-dose WTD but weaker than the high-dose WTD （<italic>P</italic><0.05）. Conclusion:WTD can relieve the articular cartilage injury in KOA mice， and the mechanism may be related to VEGF/VEGFR2/ERK1/2 signaling pathway.