Impacts of alpinetin on angiogenesis in knee osteoarthritis rats by regulating the VEGF/SphK1/S1P signaling pathway
Objective To investigate effects of alpinetin(APT)on angiogenesis in knee osteoarthritis(KOA)rats by regulating vascular endothelial growth factor/sphingosine kinase 1/sphingosine 1 phosphate(VEGF/SphK1/S1P)signaling pathway.Methods The KOA rat model was established by Videman method.Ninety rats were grouped into the control group,the model group,the low-dose kaempferol group(L-APT group),the high-dose kaempferol group(H-APT group),the high-dose kaempferol group+lentivirus negative control group(APT+NC group)and high-dose kaempferol+overexpression of SphK1 lentivirus group(APT+SphK1 group),with 15 rats in each group.Pathological changes of cartilage tissue in rats were observed by HE staining.Contents of IL-1β,TNF-α,IL-6 and MMP-13 in cartilage tissue were measured by enzyme linked immunosorbent assay.Chondrocyte apoptosis of cartilage tissue cells was detected by TUNEL.VEGF and CD31 protein positive expression levels were detected by immunohistochemistry assay.The p-VEGFR2,VEGFR2,SphK1 and S1P protein levels were detected by Western blot assay.Results Rats in the model group showed pathological damage.Compared with the control group,the apoptosis rate,IL-1β,TNF-α,IL-6,MMP-13 levels,VEGF positive expression,CD31 positive expression,p-VEGFR2,SphK1 and S1P protein expression levels were increased in the model group(P＜0.05).Compared with the model group,the pathological damage was obviously reduced in the L-APT group and the M-APT group,and cell apoptosis rate,IL-1β,TNF-α,IL-6,MMP-13 levels,VEGF positive expression,CD31 positive expression,p-VEGFR2,SphK1 and S1P protein expression levels were obviously reduced(P＜0.05).Compared with the APT+NC group,the pathological injury of cartilage tissue increased in the APT+SphK1 group,cell apoptosis rate,IL-1β,TNF-α,IL-6,MMP-13 levels,VEGF positive expression,CD31 positive expression,p-VEGFR2,SphK1 and S1P protein expression levels were obviously increased(P＜0.05).Conclusion APT inhibits angiogenesis in knee osteoarthritis rats by inhibiting the VEGF/SphK1/S1P signaling pathway.
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