Cell type‐specific effects of Notch signaling activation on intervertebral discs: Implications for intervertebral disc degeneration
| Autor: | Jun Lin, Li Ni, Zhaoyang Liu, Bin Li, Jianquan Chen, Anthony J. Mirando, Cunchang Liu, Di Chen, Yixin Zheng, Matthew J. Hilton, Saijilafu |
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| Rok vydání: | 2018 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine MMP3 Nucleus Pulposus Anabolism Physiology Interleukin-1beta Clinical Biochemistry Cell Notch signaling pathway Intervertebral Disc Degeneration Article Mice 03 medical and health sciences medicine Animals Humans Cell Lineage Receptor Notch1 Intervertebral Disc Receptors Notch Tumor Necrosis Factor-alpha Catabolism Chemistry Macrophages Annulus Fibrosus Intervertebral disc Cell Biology musculoskeletal system Chondrogenesis Rats Cell biology 030104 developmental biology medicine.anatomical_structure ADAMTS4 Gene Expression Regulation Signal Transduction |
| Zdroj: | Journal of Cellular Physiology. 233:5431-5440 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.26385 |
| Popis: | 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. Over-expression 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 Notch signaling exerted differential and cell type-specific effects in intervertebral discs, and specific Notch signaling regulation may be considered during the treatment of IVD degeneration. |
| Databáze: | OpenAIRE |
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