Polychlorinated Biphenyls 153 Exerts Pro-osteoarthritic Effects Through PI3K/AKT/ NF-κB Signaling Pathway In SW1353 Cells: A Study

Objective:To investigate the pro-osteoarthritic effects of 2,2’,4,4’,5,5’-hexachlorobiphenyl（PCB153）on osteoarthritis（OA）and whether the possible mechanism involves the PI3K/Akt/NF-κB signal pathway,and provide experimental evidence for clarifying the impact and the pathogenesis of environmental pollutants on OA.Methods:SW1353 cell line was purchased at the Cell Resource Center of the Shanghai Academy of Sciences,Chinese Academy of Sciences.The cells were cultured in DMEM medium,37°C,5%CO₂,saturated humidity incubator,and treated with PCB153 and PI3K inhibitor LY294002.CCK-8 assay was used to detect the effect of PCB153（0-50μM）on the proliferation of SW1353 cells.The expression levels of type II collagen and MMP13 in cells were detected by immunohistochemical staining.The protein expression levels of MMP13,p-PI3K,PI3K,p-Akt,Akt and p-NF-κB were detected by Western blot.The expression levels of MMP13,p-Akt,p-NF-κB in cells were detected by immunofluorescence.Results:1.Effects of different concentrations of PCB153 on the proliferation of SW1353 cells Compared with the blank control group,DMSO had no significant effect on cell proliferation activity（P>0.05）.Compared with DMSO group,PCB153（40～50μmol/L）could decrease cell proliferation activity,and the difference was statistically significant（P<0.05）.2.Effect of PCB153 on the expression of MMP13 in SW1353 cells Compared with the control group,20 and 30μM PCB153 treatment can increase the expression of MMP13 in a concentration-dependent manner（P<0.05）.3.Effect of PCB153 on the expression of type II collagen in SW1353 cells Compared with the control group,20 and 30μM PCB153 treatment reduced the expression of type II collagen in a concentration-dependent manner（P<0.05）.4.Time-response relationship of the effects of PCB153 treatment on the expression of p-Akt in SW1353 cells Compared with the control group,PCB153 treatment at different time points can cause changes in p-Akt expression levels,and the protein expression level of p-Akt increased most significantly at 0.25 h after PCB153 treatment of cells,the difference was statistically significant（P<0.05）.5.Effect of PCB153 treatment on PI3K/Akt and NF-κB signaling pathway in SW1353 cells Different concentrations of PCB153 treatment could activate PI3K/Akt and NF-κB signaling pathway in SW1353 cells,and the expression of p-PI3K,p-Akt and p-NF-κB increased in a concentration-dependent manner（P<0.05）;However,PCB153 treatment at different concentrations had no significant effect on the protein expression of PI3K and Akt（P>0.05）.6.Effects of PCB153 on NF-κB signaling pathway in SW1353 cells after pretreatment with LY294002 （1）Compared with the PCB153-treated group,LY294002 pretreatment significantly inhibited the expression of PI3K/Akt signaling pathway,and the expression levels of p-PI3K and p-Akt decreased significantly（P<0.05）;There was no significant change in the expression levels of Akt and Akt,and the difference was not statistically significant（P>0.05）.（2）Compared with the PCB153-treated group,LY294002 pretreatment significantly inhibited the expression of p-NF-κB（P<0.05）.Conclusions:1.PCB153 at a certain concentration can promote the degeneration of SW1353chondrocytes in vitro.2.The OA promoting effect of PCB153 involves PI3K/Akt/NF-κB signaling pathway.