Wu, XinghuoLiu, WeiDuan, ZhenfengGao, YongLi, ShuaiWang, KunSong, YuShao, ZengwuYang, ShuhuaYang, Cao2016-10-112016Wu, Xinghuo, Wei Liu, Zhenfeng Duan, Yong Gao, Shuai Li, Kun Wang, Yu Song, Zengwu Shao, Shuhua Yang, and Cao Yang. 2016. “The Involvement of Protease Nexin-1 (PN1) in the Pathogenesis of Intervertebral Disc (IVD) Degeneration.” Scientific Reports 6 (1): 30563. doi:10.1038/srep30563. http://dx.doi.org/10.1038/srep30563.2045-2322http://nrs.harvard.edu/urn-3:HUL.InstRepos:29002554Protease nexin-1 (PN-1) is a serine protease inhibitor belonging to the serpin superfamily. This study was undertaken to investigate the regulatory role of PN-1 in the pathogenesis of intervertebral disk (IVD) degeneration. Expression of PN-1 was detected in human IVD tissue of varying grades. Expression of both PN-1 mRNA and protein was significantly decreased in degenerated IVD, and the expression levels of PN-1 were correlated with the grade of disc degeneration. Moreover, a decrease in PN-1 expression in primary NP cells was confirmed. On induction by IL-1β, the expression of PN-1 in NP cells was decreased at day 7, 14, and 21, as shown by western blot analysis and immunofluorescence staining. PN-1 administration decreased IL-1β-induced MMPs and ADAMTS production and the loss of Agg and Col II in NP cell cultures through the ERK1/2/NF-kB signaling pathway. The changes in PN-1 expression are involved in the pathogenesis of IVD degeneration. Our findings indicate that PN-1 administration could antagonize IL-1β-induced MMPs and ADAMTS, potentially preventing degeneration of IVD tissue. This study also revealed new insights into the regulation of PN-1 expression via the ERK1/2/NF-kB signaling pathway and the role of PN-1 in the pathogenesis of IVD degeneration.en-USJournal Article2016-10-1110.1038/srep30563