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Redundant modulatory effects of proinflammatory cytokines in human osteoblastic cells in vitro
G. Di Benedetto1, L. Lempereur2, D. Valle3, E.A. Greco4, R. Bernardini5, A. Lenzi6, S. Migliaccio7
- Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, Sapienza University of Rome; and LiSa Laboratory, University Policlinico of Catania, Italy.
- LiSa Laboratory, University Policlinico of Catania, Italy.
- LiSa Laboratory, University Policlinico of Catania; and Eli Lilly Italia, Regulatory Office, Rome, Italy.
- Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, Sapienza University of Rome; and LiSa Laboratory, University Policlinico of Catania, Italy.
- Department of Biomedical and Biotechnological Sciences, Section of Pharmacology; and Clinical Toxicology Unit, Policlinico G. Rodolico, University of Catania School of Medicine, Catania, Italy.
- Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, Sapienza University of Rome, Italy.
- Department of Movement, Human and Health Sciences, Section of Health Sciences, Foro Italico University of Rome, Italy. silvia.migliaccio@uniroma4.it
CER10167
2018 Vol.36, N°6
PI 0959, PF 0969
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PMID: 29998830 [PubMed]
Received: 10/12/2016
Accepted : 26/06/2017
In Press: 25/06/2018
Published: 06/12/2018
Abstract
OBJECTIVES:
The aim of our study was to investigate possible interaction of IL-17, TRAIL, and TNF-α in the modulation of osteoblast homeostasis in vitro, using human differentiated osteoblastic Saos-2 cells as in vitro model.
METHODS:
The effects of these cytokines on osteoblastic cell viability were assessed, by MTT assay, alone or in combination, at different times and concentrations. The effects of IL-17 and TNF-α on the regulatory system of osteoclast activity RANK/RANKL/ OPG were evaluated by Western blot and ELISA techniques in cell culture media. Quantitative expression of RANKL, OPG and pro-inflammatory factors were analysed at the mRNA level by quantitative real time RT-PCR.
RESULTS:
Effects of IL-17, TNF-α and TRAIL on osteoblastic cell viability indicated that IL-17 alone, or in combination with TNF-α did not alter Saos-2 cell viability. On the other hand, TRAIL, as expected, exhibited time- and concentration-dependent cytotoxicity. The expression both RANKL and OPG were increased at the mRNA level and protein release by IL-17 and TNF-α, either alone or in combination. The analysis of IL-17 and TNF-α on pro-inflammatory molecules mRNA expression, such as CXC family chemokines CXCL-1 and CXCL-5, COX-2 and IL-6 demonstrated an increase in these pro-inflammatory cytokines with cooperative effects of the combination.
CONCLUSIONS:
Overall, these results suggest that IL-17, TRAIL and TNF-α sustain bone tissue inflammation associated with decrease of calcified component. To do so, they act redundantly each other, to amplify the inflammatory response in the bone. In conclusion, unravelling novel molecular targets within the bone-cytokine network represents a platform for innovative treatment of bone diseases due to immunological diseases such as psoriatic arthritis.
