Intervertebral disc and endplate cells response to IL-1β inflammatory cell priming and identification of molecular targets of tissue degeneration
| Autor: | Alessandra Colombini, P. De Luca, L. de Girolamo, Domenico Coviello, Diego Correa, S. Coco, Marco Brayda-Bruno, C Perucca Orfei, M. Castagnetta, Dimitrios Kouroupis |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Chemokine Cell type Necrosis endplate cells lcsh:Diseases of the musculoskeletal system medicine.medical_treatment Interleukin-1beta lcsh:Surgery Inflammation Intervertebral Disc Degeneration Motor Endplate gene array Downregulation and upregulation medicine Cluster Analysis Humans Intervertebral Disc protein array interleukin 1 beta biology Growth factor Stem Cells Interleukin Tissue Inhibitor of Metalloproteinases intervertebral disc cells lcsh:RD1-811 Middle Aged Matrix Metalloproteinases Cell biology Gene Expression Regulation biology.protein Tumor necrosis factor alpha Female medicine.symptom lcsh:RC925-935 |
| Zdroj: | European Cells & Materials, Vol 39, Pp 227-248 (2020) |
| ISSN: | 1473-2262 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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