BNIP3 decreases the LPS-induced inflammation and apoptosis of chondrocytes by promoting the development of autophagy.

Abstract

Inflammation and apoptosis of chondrocytes are the pathological bases of osteoarthritis. Autophagy could alleviate the symptoms of inflammation and apoptosis. Previous study has shown that BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) can induce the occurrence and development of autophagy. However, it is unknown whether autophagy induced by BNIP3 can alleviate the inflammation and apoptosis of chondrocytes. We used the lentivirus to construct the overexpression BNIP3 chondrocytes. Next, the lipopolysaccharide (LPS) was used to stimulate these cells to simulate the physiological environment of osteoarthritis. After that, the enzyme-linked immunosorbent assays (ELISA) were performed to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) and the flow cytometry was performed to detect the apoptosis rates of chondrocytes. At last, the expression of autophagy-related proteins was detected with the western blotting. The expression of BNIP3 was suppressed after treatment with LPS. However, overexpression of BNIP3 inhibited the secretion of proinflammatory factors (TNF-α, IL-1β, and IL-6) and decreased the apoptosis of chondrocytes. Furthermore, overexpression of BNIP3 led to the upregulation of autophagy-related protein expression including little computer 3 (LC3), autophagy-related protein 7 (ATG7), and Beclin-1. Application of autophagy inhibitor recovered the expression of proinflammatory factors and apoptosis rates of chondrocytes. BNIP3 decreased the LPS-induced inflammation and apoptosis of chondrocytes by activating the autophagy.