HtrA1 upregulates the expression of ADAMTS-5 in HNPCs via the ERK/NF-κB/JNK signaling pathway.

Intervertebral disc degeneration (IDD) is a form of chronic inflammation and is one of the most common disorders reported to be involved in low back pain (LBP). The pathophysiology of degeneration is not completely understood, but the consensus is that the degradation of extracellular matrix (ECM) proteins in the disc is the leading factor contributing to IDD. High temperature requirement A1 (HtrA1) is serine protease that has been shown to be increased in degenerated intervertebral discs as a result of an increase in the expression of matrix metalloproteinases (MMPs), but no study has focused on the effect of HtrA1 on a disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTSs). In the present study, we successfully isolated human nucleus pulposus cells (HNPCs) from IDD patients who were our research subjects to elaborate on the potential role of HtrA1 in the pathogenesis of IDD. We confirmed that HtrA1 has the potential to induce the expression of ADAMTS-5 in a dose-dependent manner. Consistently, this was mediated by the ERK, NF-κB and JNK pathways. By using inhibitors of these pathways, the increase in ADAMTS-5 could be reduced. Our findings indicated that HtrA1 can induce the expression of ADAMTS-5 in HNPCs via the ERK/NF-κB/JNK signaling pathway, and our study also elucidated the involved induction mechanisms in HNPCs, which may provide new insights for the treatment of IDD.