Research Paper|Volume 10, Issue 8|pp 2001—2015

MicroRNA-221 silencing attenuates the degenerated phenotype of intervertebral disc cells

Letizia Penolazzi¹, Elisabetta Lambertini¹, Leticia Scussel Bergamin¹, Tosca Roncada¹, Pasquale De Bonis², Michele Cavallo², Roberta Piva^1,³

¹Department of Biomedical and Specialty Surgical Sciences, University of Ferrara, Ferrara, Italy
²Department of Neurosurgery, S. Anna University Hospital, Ferrara, Italy
³Center for Studies on Gender Medicine, University of Ferrara, Ferrara, Italy

Received: February 22, 2018Accepted: August 8, 2018Published: August 20, 2018

https://doi.org/10.18632/aging.101525

Copyright: © 2018 Penolazzi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The aim of this study was to investigate the role of an antichondrogenic factor, MIR221 (miR-221), in intervertebral disc degeneration (IDD), and provide basic information for the development of a therapeutic strategy for the disc repair based on specific nucleic acid based drugs, such as miR-221 silencing. We established a relatively quick protocol to minimize artifacts from extended in vitro culture, without selecting the different types of cells from intervertebral disc (IVD) or completely disrupting extracellular matrix (ECM), but by using the whole cell population with a part of resident ECM. During the de-differentiation process miR-221 expression significantly increased. We demonstrated the effectiveness of miR-221 silencing in driving the cells towards chondrogenic lineage. AntagomiR-221 treated cells showed in fact a significant increase of expression of typical chondrogenic markers including COL2A1, ACAN and SOX9, whose loss is associated with IDD. Moreover, antagomiR-221 treatment restored FOXO3 expression and increased TRPS1 expression levels attenuating the severity grade of degeneration, and demonstrating in a context of tissue degeneration and inflammation not investigated before, that FOXO3 is target of miR-221. Data of present study are promising in the definition of new molecules useful as potential intradiscal injectable biological agents.