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.
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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.
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.
Soundharrajan, Ilavenil; Kim, Da Hye; Kuppusamy, Palaniselvam; and Choi, Ki Choon, "Modulation of Osteogenic and Myogenic Differentiation by a Phytoestrogen Formononetin via p38MAPK-Dependent JAK-STAT and Smad-1/5/8 Signaling Pathways in Mouse Myogenic Progenitor Cells" (2019). Center for Research on Environmental Disease Faculty Publications. 11.