@article{22309156083045e081c549abedef1390,
title = "Intervertebral disc and endplate cells response to il-1β inflammatory cell priming and identification of molecular targets of tissue degeneration",
abstract = "Inflammation represents an important factor leading to metabolic imbalance within the intervertebral disc (IVD), conducive to degenerative changes. Therefore, a thorough knowledge of the IVD and endplate (EP) cell behaviour in such pathological environments is essential when designing regenerative therapeutic strategies. The present study aimed at assessing the molecular response of the IVD constitutive nucleus pulposus (NPCs)-, annulus fibrosus (AFCs)-and endplate (EPCs)-derived cells to interleukin (IL)-1β treatment, through large-scale, high-throughput microarray and protein analysis, identifying the differentially expressed genes and released proteins. Overall, the inflammatory stimulus downregulated stemness genes while upregulating pro-inflammatory, pro-angiogenic and catabolic genes, including matrix metalloproteases, which were not balanced by a concomitant upregulation of their inhibitors. Upregulation of anti-inflammatory and anabolic tumour necrosis factor inducible gene 6 protein (TNFAIP6), of IL-1 receptor antagonist (IL-1Ra) (at gene and protein levels) and of trophic insulin-like growth factor 1 (IGF1) was also observed in all cell types; IGF1 particularly in AFCs. An overall inhibitory effect of tumour necrosis factor alpha (TNFα) signal was observed in all cell types; however, EPCs showed the strongest anti-inflammatory behaviour. AFCs and EPCs shared the ability to limit the activation of the signalling mediated by specific chemokines. AFCs showed a slightly senescent attitude, with a downregulation of genes related to DNA repair or pro-mitosis. Results allowed for the identification of specific molecular targets in IVD and EP cells that respond to an inflammatory environment. Such targets can be either silenced (when pathological targets) or stimulated to counteract the inflammation.",
keywords = "Endplate cells, Gene array, Inflammatiomarkers, Interleukin 1 beta, Intervertebral disc cells, Protein array",
author = "{De Luca}, P. and {de Girolamo}, L. and D. Kouroupis and M. Castagnetta and {Perucca Orfei}, C. and D. Coviello and S. Coco and D. Correa and M. Brayda-Bruno and A. Colombini",
note = "Funding Information: The study was funded by the Italian Ministry of Health, ?Ricerca Corrente?. Diego Correa and Dimitrios Kouroupis thank the Soffer Family Foundation and the Diabetes Research Institute Foundation (DRIF) for their generous funding support. These funding sources were not involved in any step of the study design, collection, analysis, interpretation of the data or writing of the manuscript. Diego Correa is a paid consultant of Lipogems USA, LLC. The other authors declare no conflict of interest. Funding Information: IVD (Asahara et al., 1996) cells is NO. In agreement with previously reported upregulation of iNOS and The study was funded by the Italian Ministry of Health, NO in NPCs after IL-1A蘂?treatment (eBt aail., 2019), “Ricerca Corrente”. Diego Correa and Dimitrios after the same inflammatory stimulation, NOS2 was Kouroupis thank the Soffer Family Foundation and upregulated in all the analysed disc and EP cells. In the Diabetes Research Institute Foundation (DRIF) addition, it was observed in cerebrospinal fluid of for their generous funding support. These funding patients affected by degenerative lumbar disease sources were not involved in any step of the study (Asahara et al., 1996). design, collection, analysis, interpretation of the data Concerning the angiogenic-related genes or writing of the manuscript. evaluated, all the cell populations showed a slight Diego Correa is a paid consultant of Lipogems pro-angiogenic behaviour after inflammation, with USA, LLC. The other authors declare no conflict of no inter-population difference. This is in line with interest. what previously reported for human degenerated or inflamed IVDs (Binch et al., 2014). Between all the analysed cells, AFCs had a slightly Publisher Copyright: {\textcopyright} 2020, AO Research Institute Davos. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = jan,
day = "1",
doi = "10.22203/eCM.v039al5",
language = "English (US)",
volume = "39",
pages = "227--248",
journal = "European Cells and Materials",
issn = "1473-2262",
publisher = "Swiss Society for Biomaterials",
}