Formononetin (FN), a typical phytoestrogen has attracted substantial attention as a novel agent because of its diverse biological activities including, osteogenic differentiation. However, the molecular mechanisms underlying osteogenic and myogenic differentiation by FN in C2C12 progenitor cells remain unknown. Therefore the objective of the current study was to investigate the action of FN on myogenic and osteogenic differentiation and its impact on signaling pathways in C2C12 cells. FN significantly increased myogenic markers such as Myogenin, myosin heavy chains, and myogenic differentiation 1 (MyoD). In addition, the expression of osteogenic specific genes alkaline phosphatase (ALP), Run-related transcription factor 2(RUNX2), and osteocalcin (OCN) were up-regulated by FN treatment. Moreover, FN enhanced the ALP level, calcium deposition and the expression of bone morphogenetic protein isoform (BMPs). Signal transduction pathways mediated by p38 mitogen-activated protein kinase (p38MAPK), extracellular signal-related kinases (ERKs), protein kinase B (Akt), Janus kinases (JAKs), and signal transducer activator of transcription proteins (STATs) in myogenic and osteogenic differentiation after FN treatment were also examined. FN treatment activates myogenic differentiation by increasing p38MAPK and decreasing JAK1-STAT1 phosphorylation levels, while osteogenic induction was enhanced by p38MAPK dependent Smad, 1/5/8 signaling pathways in C2C12 progenitor cells.

Document Type


Publication Date


Notes/Citation Information

Published in Scientific Reports, v. 9, article no. 9307, p. 1-12.

© The Author(s) 2019

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Digital Object Identifier (DOI)


Funding Information

Cooperative Research Program for Agriculture Science and Technology Development provided supports for this research work (Project No. PJ010903022017). The project titled Technical development to increase utilization of Italian ryegrass in livestock” sponsored by RDA, Korea. This study was also supported by the Postdoctoral Fellowship Program of the National Institute of Animal Science funded by RDA, Korea.

Related Content

The data generated and analyzed for the current study are available from the corresponding author upon reasonable request.

Supplementary information accompanies this paper at https://doi.org/10.1038/s41598-019-45793-w.

41598_2019_45793_MOESM1_ESM.pdf (612 kB)
Supplementary Information