Modulation of miR-204 Expression during Chondrogenesis
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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-02-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/4/2130 |
| _version_ | 1797479371559141376 |
|---|---|
| author | Luca Dalle Carbonare Jessica Bertacco Arianna Minoia Mattia Cominacini Lekhana Bhandary Rossella Elia Giovanni Gambaro Monica Mottes Maria Teresa Valenti |
| author_facet | Luca Dalle Carbonare Jessica Bertacco Arianna Minoia Mattia Cominacini Lekhana Bhandary Rossella Elia Giovanni Gambaro Monica Mottes Maria Teresa Valenti |
| author_sort | Luca Dalle Carbonare |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T21:44:54Z |
| format | Article |
| id | doaj.art-47a4b548cf504b308e0d901acc554efa |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:44:54Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-47a4b548cf504b308e0d901acc554efa2023-11-23T20:20:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234213010.3390/ijms23042130Modulation of miR-204 Expression during ChondrogenesisLuca Dalle Carbonare0Jessica Bertacco1Arianna Minoia2Mattia Cominacini3Lekhana Bhandary4Rossella Elia5Giovanni Gambaro6Monica Mottes7Maria Teresa Valenti8Department of Medicine, University of Verona, 37100 Verona, ItalyDepartment of Medicine, University of Verona, 37100 Verona, ItalyDepartment of Medicine, University of Verona, 37100 Verona, ItalyDepartment of Medicine, University of Verona, 37100 Verona, ItalyFlaskworks, LLC, 38 Wareham St, Boston, MA 02118, USADepartment of Medicine, University of Verona, 37100 Verona, ItalyDepartment of Medicine, University of Verona, 37100 Verona, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37100 Verona, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, 37100 Verona, ItalyRUNX2 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.https://www.mdpi.com/1422-0067/23/4/2130chondrogenesismiR-204mesenchymal stem cellsRUNX2 |
| spellingShingle | Luca Dalle Carbonare Jessica Bertacco Arianna Minoia Mattia Cominacini Lekhana Bhandary Rossella Elia Giovanni Gambaro Monica Mottes Maria Teresa Valenti Modulation of miR-204 Expression during Chondrogenesis International Journal of Molecular Sciences chondrogenesis miR-204 mesenchymal stem cells RUNX2 |
| title | Modulation of miR-204 Expression during Chondrogenesis |
| title_full | Modulation of miR-204 Expression during Chondrogenesis |
| title_fullStr | Modulation of miR-204 Expression during Chondrogenesis |
| title_full_unstemmed | Modulation of miR-204 Expression during Chondrogenesis |
| title_short | Modulation of miR-204 Expression during Chondrogenesis |
| title_sort | modulation of mir 204 expression during chondrogenesis |
| topic | chondrogenesis miR-204 mesenchymal stem cells RUNX2 |
| url | https://www.mdpi.com/1422-0067/23/4/2130 |
| work_keys_str_mv | AT lucadallecarbonare modulationofmir204expressionduringchondrogenesis AT jessicabertacco modulationofmir204expressionduringchondrogenesis AT ariannaminoia modulationofmir204expressionduringchondrogenesis AT mattiacominacini modulationofmir204expressionduringchondrogenesis AT lekhanabhandary modulationofmir204expressionduringchondrogenesis AT rossellaelia modulationofmir204expressionduringchondrogenesis AT giovannigambaro modulationofmir204expressionduringchondrogenesis AT monicamottes modulationofmir204expressionduringchondrogenesis AT mariateresavalenti modulationofmir204expressionduringchondrogenesis |