Myocardin-Related Transcription Factor A (MRTF-A)‎ Regulates the Balance between Adipogenesis and Osteogenesis of Human Adipose Stem Cells

Joint Authors

Miettinen, Susanna
Hyväri, Laura
Vanhatupa, Sari
Halonen, Heidi T.
Kääriäinen, Minna

Source

Stem Cells International

Issue

Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-17, 17 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2020-09-22

Country of Publication

Egypt

No. of Pages

17

Abstract EN

Previous studies have demonstrated that myocardin-related transcription factor A (MRTF-A) generates a link between the dynamics of the actin cytoskeleton and gene expression with its coregulator, serum response factor (SRF).

MRTF-A has also been suggested as a regulator of stem cell differentiation.

However, the role of MRTF-A in human mesenchymal stem cell differentiation remains understudied.

We aimed to elucidate whether MRTF-A is a potential regulator of human adipose stem cell (hASC) differentiation towards adipogenic and osteogenic lineages.

To study the role of MRTF-A activity in the differentiation process, hASCs were cultured in adipogenic and osteogenic media supplemented with inhibitor molecules CCG-1423 or CCG-100602 that have been shown to block the expression of MRTF-A/SRF-activated genes.

Our results of image-based quantification of Oil Red O stained lipid droplets and perilipin 1 staining denote that MRTF-A inhibition enhanced the adipogenic differentiation.

On the contrary, MRTF-A inhibition led to diminished activity of an early osteogenic marker alkaline phosphatase, and export of extracellular matrix (ECM) proteins collagen type I and osteopontin.

Also, quantitative Alizarin Red staining representing ECM mineralization was significantly decreased under MRTF-A inhibition.

Image-based analysis of Phalloidin staining revealed that MRTF-A inhibition reduced the F-actin formation and parallel orientation of the actin filaments.

Additionally, MRTF-A inhibition affected the protein amounts of α-smooth muscle actin (α-SMA), myosin light chain (MLC), and phosphorylated MLC suggesting that MRTF-A would regulate differentiation through SRF activity.

Our results strongly indicate that MRTF-A is an important regulator of the balance between osteogenesis and adipogenesis of hASCs through its role in mediating the cytoskeletal dynamics.

These results provide MRTF-A as a new interesting target for guiding the stem cell differentiation in tissue engineering applications for regenerative medicine.

American Psychological Association (APA)

Hyväri, Laura& Vanhatupa, Sari& Halonen, Heidi T.& Kääriäinen, Minna& Miettinen, Susanna. 2020. Myocardin-Related Transcription Factor A (MRTF-A) Regulates the Balance between Adipogenesis and Osteogenesis of Human Adipose Stem Cells. Stem Cells International،Vol. 2020, no. 2020, pp.1-17.
https://search.emarefa.net/detail/BIM-1207987

Modern Language Association (MLA)

Hyväri, Laura…[et al.]. Myocardin-Related Transcription Factor A (MRTF-A) Regulates the Balance between Adipogenesis and Osteogenesis of Human Adipose Stem Cells. Stem Cells International No. 2020 (2020), pp.1-17.
https://search.emarefa.net/detail/BIM-1207987

American Medical Association (AMA)

Hyväri, Laura& Vanhatupa, Sari& Halonen, Heidi T.& Kääriäinen, Minna& Miettinen, Susanna. Myocardin-Related Transcription Factor A (MRTF-A) Regulates the Balance between Adipogenesis and Osteogenesis of Human Adipose Stem Cells. Stem Cells International. 2020. Vol. 2020, no. 2020, pp.1-17.
https://search.emarefa.net/detail/BIM-1207987

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1207987