Hesperedin promotes MyoD-induced myogenic differentiation in vitro and in vivo.
OBJECTIVE
The bioflavonoid, hesperedin, promotes osteoblast differentiation in human mesenchymal stem cells, indicating an anabolic effect of hesperedin on bone metabolism. Murine bone marrow mesenchymal stem cells undergo myogenic differentiation as well as osteogenic differentiation. We therefore explored whether hesperedin modulates muscle cell differentiation.


METHODS
Myoblast C2C12 cells were differentiated into muscle cells in the presence or absence of hesperedin. The effects of hesperedin on myogenic differentiation were determined by analysing specific muscle markers in vitro using reporter gene assays, immunoblotting, RT-PCR and DNA pull-down assays. In vivo, the effects of hesperedin were assessed using the freeze injury-induced muscle regeneration model in mice and daily injections of hesperedin for 6 days.


RESULTS
Hesperedin promoted myogenic differentiation, in a dose-dependent manner, by increasing myogenin gene expression. MyoD-induced myogenin gene transcription was enhanced by hesperedin, as this bioflavonoid augmented the nuclear localization and myogenin promoter-binding of MyoD. In addition, hesperedin increased myogenin and muscle creatine kinase gene expression during myogenic differentiation from C3H10T1/2 mesenchymal stem cells in a MyoD-dependent manner and accelerated in vivo muscle regeneration induced by muscle injury.


CONCLUSIONS
Our results demonstrate that hesperedin promoted myogenic differentiation in vitro and in vivo through activation of MyoD-mediated myogenin expression, suggesting a beneficial role in promoting muscle regeneration, following injury.
College of Pharmacy, Division of Life and Pharmaceutical Sciences, Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul, Korea.
Hana
H
Jeong
Joo Yeon
JY
Lee
Eun Jung
EJ
Jang
Eun Hye
EH
Lee
Myung Ae
MA
Bae
Jeong-Ho
JH
Hong
Eun Sook
ES
Hwang
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D054338:Cell Transdifferentiation; D052283:Creatine Kinase, MM Form / Q000096:biosynthesis; D004247:DNA / Q000378:metabolism; D015870:Gene Expression; D006569:Hesperidin / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000293:injuries / Q000502:physiology; D017570:MyoD Protein / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018008:Myogenin / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012038:Regeneration / Q000187:drug effects
D017570:MyoD Protein; D018008:Myogenin; D004247:DNA; D006569:Hesperidin; D052283:Creatine Kinase, MM Form
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