Cell type-specific effects of Notch signaling activation on intervertebral discs: Implications for intervertebral disc degeneration

Journal of Cellular Physiology
Yixin ZhengJianquan Chen

Abstract

Intervertebral disc (IVD) degeneration is the major cause of back pain. Notch signaling is activated in annulus fibrosus (AF) and nucleus pulposus (NP) tissues of degenerated IVDs, and induced by IL1-β and TNF-α in NP cells. However, the role of Notch activatin in the pathogenesis of IVD degeneration is largely unknown. In this study, we overexpressed the Notch1 intracellular domain (NICD1) in AF, NP, and chondrogenic ATDC5 cells via adenoviruses. Overexpression of NICD1 activated transcription of Notch signaling target genes in AF, NP, and ATDC5 cells, and caused cell type-specific effects on expression of matrix anabolic and catabolic genes. Activation of Notch signaling promoted expression of matrix catabolic genes and inhibited expression of matrix anabolic genes in both AF and ATDC5 cells, whereas its activation suppressed expression of matrix catabolic genes (including Mmp3, Mmp13, Adamts4, and Adamts5) and attenuated TNF-α and inflammatory macrophage-induced Mmp13 expression in NP cells. Consistently, sustained activation of Notch1 signaling in postnatal IVDs in mice severely disrupted growth plate and endplate cartilage tissues, but did not overly affect NP tissues. Together, these data indicated that activation of Notc...Continue Reading

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Citations

Aug 31, 2018·Journal of Cellular Biochemistry·Qingbai LiuJianquan Chen
Oct 15, 2018·Journal of Cellular Physiology·Kun LiJianquan Chen
Dec 29, 2020·Frontiers in Cell and Developmental Biology·Dong WangLiu Yang
Jul 20, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Greig CouasnayFlorent Elefteriou
Nov 20, 2021·PLoS Computational Biology·Diego Barra AvilaXiao-Jun Tian

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