Hypoxia inhibits chondrocyte pyroptosis via HIF1α/NIX-mediated mitochondrial autophagy
10.16781/j.CN31-2187/R.20240552
- VernacularTitle:低氧通过HIF1α/NIX介导的线粒体自噬抑制软骨细胞焦亡
- Author:
Shiqi LUO
1
;
Xia WEI
;
Lang JIA
Author Information
1. 重庆医科大学附属第二医院康复科,重庆 400010
- Keywords:
hypoxia;
mitochphagy;
osteoarthritis;
chondrocytes;
pyroptosis
- From:
Academic Journal of Naval Medical University
2025;46(5):594-601
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effect of hypoxia(HX)on autophagy and pyroptosis-related protein expression of interleukin(IL)-1β-induced chondrocytes,and explore its mechanism of cartilage protection.Methods The expression of Bcl2/adenovirus E1B interacting protein 3-like(BNIP3L/NIX)in normal and osteoarthritis chondrocytes was analyzed by bioinformatics method.The primary chondrocytes from the knee joints of C57BL/6J neonatal mice were extracted and assigned to control group,IL-1β group,HX group,or IL-1β+HX group.The cells were treated with 10 ng/mL IL-1β for 24 h to simulate osteoarthritis-like chondrocyte injury,and HX treatment was by incubation with 1%O2 for 24 h.The expression levels of collagen typeⅡ α1(COL2α1),matrix metalloproteinase 13(MMP13),a disintegrin and metalloproteinase with thrombospondin 5(ADAMTS5),nucleotide-binding oligomerization domain-like receptor 3(NLRP3),gasdermin D N-terminal domain(GSDMD-N),apoptosis-associated speck-like protein containing a CARD(ASC),IL-18,hypoxia induced factor 1α(HIF1α),NIX,Beclin1,microtubule-associated protein-light chain 3(LC3),and p62 proteins were detected by Western blotting in each group.Results Bioinformatics analysis showed that the expression of NIX was lower in osteoarthritis chondrocytes than in normal chondrocytes.Western blotting showed that compared to the control group,the IL-1β group showed significant decreases in COL2α1 and NIX protein expression(both P＜0.05)and significant increases in MMP13,ADAMTS5,NLRP3,GSDMD-N,ASC,IL-18 and HIF1α protein expression(all P＜0.01).Compared to the IL-1β group,the IL-1β+HX group showed significant increases in COL2α1,HIF1α,NIX,Beclin1,and LC3 Ⅱ/LC3Ⅰ(all P＜0.01)and significant decreases in MMP13,ADAMTS5,NLRP3,GSDMD-N,ASC,IL-18 and p62(all P＜0.01).Compared to the control group,the HX group exhibited significant increases in HIF1α,NIX,Beclin1,and LC3Ⅱ/LC3Ⅰ(all P＜0.01)and decreases in p62,NLRP3,GSDMD-N and IL-18(all P＜0.05).Conclusion Hypoxia may eliminate NLRP3 inflammasome and inhibit chondrocyte pyroptosis through HIF1α/NIX-mediated mitochondrial autophagy,thereby reducing IL-1β-induced chondrocyte injury.
