HtrA1 up-regulates expression of MMPs via Erk1/2/Rock-dependent pathways

Abstract

Background: There are few studies that have identified the potential role of a high temperature requirement A1 (HtrA1) in intervertebral disc degeneration (IDD). This study was undertaken to investigate the regulatory role of HtrA1 in the pathogenesis of IDD. Material and Methods: The mRNA levels of HtrA1 and matrix metalloproteinases (MMPs) of human intervertebral disc degeneration tissues were measured by real-time quantitative PCR, and a correlation between the expression level of HtrA1 and MMPs was also investigated. Human nucleus pulposus cells (HNPCs) were challenged with rHtrA1, and expression of MMPs was measured by real-time quantitative PCR, Western blotting, and ELISA. Moreover, to analyze the mechanism by which HtrA1 up-regulates MMPs, ERK1/2/ ROCK signaling pathway inhibitors were also used. Results: We found significant increases in mRNA expression of HtrA1 and MMP1, 3, 9, and 13 in IDD tissues compared with control. HtrA1 expression level was associated with the levels of MMP1, 3, and 13. Expression of MMP1, 3, and 13 mRNA and protein were significantly increased in HNPCs treated by rHtrA1. Moreover, administration of the ERK1/2 signaling pathway inhibitor or ROCK signaling pathway inhibitor decreased rHtrA1-induced MMPs production. Therefore, changes in HtrA1 expression could be involved in the pathogenesis of IDD. Conclusion: Our findings indicate that HtrA1 can induce increases in MMPs in HNPCs via the ERK1/2/ROCK signaling pathway, thus providing new insights into the role of HtrA1 in the pathogenesis of IDD