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
References
Jun 29, 2000·Journal of Spinal Disorders·B F Walker
Apr 16, 2002·Molecular Pathology : MP·J I SiveA J Freemont
Dec 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·L Charles MurtaughDouglas A Melton
Jan 30, 2004·The Spine Journal : Official Journal of the North American Spine Society·Helen E GruberEdward N Hanley
Mar 24, 2005·Nucleic Acids Research·Gusztav BeltekiAndras Nagy
Aug 19, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ben Z StangerDouglas A Melton
Sep 18, 2007·Genesis : the Journal of Genetics and Development·Mandar Deepak MuzumdarLiqun Luo
Dec 24, 2008·European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society·Johannes Leendert BronTheodoor H Smit
Jan 8, 2009·Spine·Kern SinghGabriella Cs-Szabo
May 14, 2009·Arthritis Research & Therapy·S Jane Millward-SadlerJudith A Hoyland
Jul 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Timothy J Mead, Katherine E Yutzey
Dec 2, 2010·Nature Reviews. Rheumatology·Dick Heinegård, Tore Saxne
Feb 10, 2011·Arthritis and Rheumatism·Akihiko HiyamaMakarand V Risbud
Jun 17, 2011·Journal of Cellular Physiology·Jae-Sung KimHee-Jeong Im
Oct 27, 2011·Disease Models & Mechanisms·Matthew R McCannCheryle A Séguin
Dec 17, 2011·Annals of the New York Academy of Sciences·Meina WangDi Chen
Mar 17, 2012·Arthritis and Rheumatism·Meina WangDi Chen
Mar 6, 2013·Journal of Cellular Physiology·Jae-Sung KimHee-Jeong Im
Apr 17, 2013·The Journal of Biological Chemistry·Hua WangMakarand V Risbud
Jun 5, 2013·Journal of Cell Science·Kazuya HoriSpyros Artavanis-Tsakonas
Jul 11, 2013·Arthritis and Rheumatism·Anthony J MirandoMatthew J Hilton
Aug 21, 2013·Osteoarthritis and Cartilage·S Zanotti, E Canalis
Oct 30, 2013·Nature Reviews. Rheumatology·Makarand V Risbud, Irving M Shapiro
Jul 23, 2015·Science Signaling·Zhaoyang LiuMatthew J Hilton
Nov 3, 2015·Osteoarthritis and Cartilage·Zhaoyang LiuMatthew J Hilton
Dec 24, 2015·Spine·Chun-do OhDi Chen
Sep 9, 2016·Journal of Cellular Biochemistry·Ming JiangJianquan Chen
Feb 6, 2017·Bone Research·Di ChenHee-Jeong Im
Aug 31, 2017·Journal of Cellular Biochemistry·Xiaohui GuJianquan Chen
Citations
Aug 31, 2018·Journal of Cellular Biochemistry·Qingbai LiuJianquan Chen
Oct 15, 2018·Journal of Cellular Physiology·Kun LiJianquan Chen
Oct 28, 2018·Journal of Cellular Physiology·Li NiJianquan Chen
Jan 25, 2019·Journal of Cellular Physiology·Yixin ZhengJianquan Chen
Jun 13, 2019·Journal of Cellular Physiology·Sarthak MohantyChitra Lekha Dahia
Jul 30, 2020·BMC Musculoskeletal Disorders·Zekang XiongXiaodong Guo
Dec 29, 2020·Frontiers in Cell and Developmental Biology·Dong WangLiu Yang
Mar 16, 2021·Molecular and Cellular Biochemistry·Huang ChenLin Fan
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 5, 2021·Cell Death & Disease·Zheng PengHuining Liu
Nov 20, 2021·PLoS Computational Biology·Diego Barra AvilaXiao-Jun Tian