Icariin interferes with TDP43-induced inflammatory factor secretion and inhibits the JNK and p38 MAPK signaling pathway in vitro

Introduction To investigate the molecular mechanism of icariin (ICA) intervention in TDP-43 mediated chondrocyte lesions of osteoarthritis. Material and methods HC-α chondrocytes were transfected with TDP-43 lentiviruses to generate TDP-43-overexpressing chondrocytes and treated with 5 μg/mL icariin. The level of TDP-43, JNK, p38 MAPK and relative factors were detected by Western blotting assays. TNF-α and IL-1β in the supernatant were determined by ELISA. Results Compared with the HC-α group, TDP-43 expression was significantly increased in the TDP-43-HC-α group and was not significantly different that of the HC-α+ICA group. However, TDP-43 expression in the TDP-43-HC-α+ICA group was significantly lower than that in the TDP-43-HC-α group. ELISA showed that the secretion of TNF-α and IL-1β in the supernatant of the TDP-43-HC-α group was significantly increased (P<0.01) compared with the HC-α group, but was significantly lower in the supernatant of the TDP-43-HC-α+ICA group than that of the TDP-43-HC-α group (P<0.01). ICA treatment reduced the expression of TDP-43 in chondrocytes and inhibited the elevation of inflammatory cytokines caused by TDP-43. ICA processing can also inhibit the activation of JNK/p38 MAPK related signaling pathways caused by TDP-43. Overexpression of TDP-43 reduced the formation of stress granules (SGs)in chondrocytes, and increased receptor for activated protein kinase C1 (RACK1) level. ICA could reverse these changes. Conclusions Icariin could interfere with TDP-43-induced secretion of inflammatory factors, inhibit JNK/p38 MAPK signaling. Our findings provided a new theoretical basis for the treatment of osteoarthritis.