A decrease in IL-33 regulates matrix degradation and apoptosis in intervertebral disc degeneration via HIF-1alpha

Low back pain (LBP) is a common aging-associated disease that can cause disability in old people. Previous research revealed that an imbalance in the extracellular matrix (ECM) via abnormal hypoxia-inducible factor-1alpha (HIF-1 alpha) expression in nucleus pulposus (NP) cells was one of the key factors in the pathogenesis of intervertebral disc degeneration (IDD). However, the mechanism by which the ECM is reduced in patients with IDD is not fully understood. Here, we reported that a new member of the interleukin (IL)-1 family, IL-33, was positively correlated with HIF-1 alpha and was decreased in the NP cells of individuals with IDD. IL-33 overexpression in degenerative NP cells decreased the levels of matrix metalloproteinase-3/13 (MMP-3/13), a disintegrin and metallo-proteinase with thrombospondin motifs-4/5 (ADAMTS-4/5), and promoted ECM expression in vitro. Furthermore, we preliminarily explored the antiapoptotic effects of IL-33, which could reduce the expression of Caspase-3 and promote the level of Bcl-2 in degenerative NP cells. Furthermore, when HIF-1 alpha expression was silenced, IL-33-mediated upregulation of ECM expression was weakened. Thus, IL-33-induced HIF-1 alpha upregulation may represent a novel therapeutic strategy to ameliorate IDD in patients with LBP.