PUBLICATION

Modulation of miR-204 Expression during Chondrogenesis

Authors

Dalle Carbonare, L., Bertacco, J., Minoia, A., Cominacini, M., Bhandary, L., Elia, R., Gambaro, G., Mottes, M., Valenti, M.T.

ID

ZDB-PUB-220227-8

Date

2022

Source

International Journal of Molecular Sciences 23(4): (Journal)

Registered Authors

Keywords

RUNX2, chondrogenesis, mesenchymal stem cells, miR-204

MeSH Terms

Zebrafish
Chondrogenesis/genetics*
Mesenchymal Stem Cells/physiology
SOX9 Transcription Factor/genetics
Animals
Down-Regulation/genetics
Cell Differentiation/genetics
MicroRNAs/genetics*
Stem Cells/physiology
Chondrocytes/physiology
Core Binding Factor Alpha 1 Subunit/genetics
Cells, Cultured
Transcriptional Activation/genetics
Humans
Osteogenesis/genetics
Up-Regulation/genetics

PubMed

35216245 Full text @ Int. J. Mol. Sci.

Abstract

RUNX2 and SOX9 are two pivotal transcriptional regulators of chondrogenesis. It has been demonstrated that RUNX2 and SOX9 physically interact; RUNX2 transactivation may be inhibited by SOX9. In addition, RUNX2 exerts reciprocal inhibition on SOX9 transactivity. Epigenetic control of gene expression plays a major role in the alternative differentiation fates of stem cells; in particular, it has been reported that SOX9 can promote the expression of miRNA (miR)-204. Our aim was therefore to investigate the miR-204-5p role during chondrogenesis and to identify the relationship between this miR and the transcription factors plus downstream genes involved in chondrogenic commitment and differentiation. To evaluate the role of miR-204 in chondrogenesis, we performed in vitro transfection experiments by using Mesenchymal Stem Cells (MSCs). We also evaluated miR-204-5p expression in zebrafish models (adults and larvae). By silencing miR-204 during the early differentiation phase, we observed the upregulation of SOX9 and chondrogenic related genes compared to controls. In addition, we observed the upregulation of COL1A1 (a RUNX2 downstream gene), whereas RUNX2 expression of RUNX2 was slightly affected compared to controls. However, RUNX2 protein levels increased in miR-204-silenced cells. The positive effects of miR204 silencing on osteogenic differentiation were also observed in the intermediate phase of osteogenic differentiation. On the contrary, chondrocytes' maturation was considerably affected by miR-204 downregulation. In conclusion, our results suggest that miR-204 negatively regulates the osteochondrogenic commitment of MSCs, while it positively regulates chondrocytes' maturation.

Genes / Markers

Figures