Nonionizing radiation as a noninvasive strategy in regenerative medicine: the effect of Ca(2+)-ICR on mouse skeletal muscle cell growth and differentiation.
Controlling cell differentiation and proliferation with minimal manipulation is one of the most important goals for cell therapy in clinical applications. In this work, we evaluated the hypothesis that the exposure of myoblast cells (C2C12) to nonionizing radiation (tuned at an extremely low-frequency electromagnetic field at calcium-ion cyclotron frequency of 13.75 Hz) may drive their differentiation toward a myogenic phenotype. C2C12 cells exposed to calcium-ion cyclotron resonance (Ca(2+)-ICR) showed a decrease in cellular growth and an increase in the G(0)/G(1) phase. Severe modifications in the shape and morphology and a change in the actin distribution were revealed by the phalloidin fluorescence analysis. A significant upregulation at transcriptional and translational levels of muscle differentiation markers such as myogenin (MYOG), muscle creatine kinase (MCK), and alpha skeletal muscle actin (ASMA) was observed in exposed C2C12 cells. Moreover, the pretreatment with nifedipine (an L-type voltage-gated Ca(2+) channel blocker) led to a reduction of the Ca(2+)-ICR effect. Consequently, it induced a downregulation of the MYOG, MCK, and ASMA mRNA expression affecting adversely the differentiation process. Therefore, our data suggest that Ca(2+)-ICR exposure can upregulate C2C12 differentiation. Although further studies are needed, these results may have important implications in myodegenerative pathology therapies.
Institute of Translational Pharmacology, National Research Council, Rome, Italy.
Flavia
F
De Carlo
Mario
M
Ledda
Deleana
D
Pozzi
Pasquale
P
Pierimarchi
Manuela
M
Zonfrillo
Livio
L
Giuliani
Enrico
E
D'Emilia
Alberto
A
Foletti
Riccardo
R
Scorretti
Settimio
S
Grimaldi
Antonella
A
Lisi
D000199:Actins / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D048430:Cell Shape / Q000187:drug effects / Q000528:radiation effects; D017357:Cyclotrons; D004247:DNA / Q000096:biosynthesis; D005453:Fluorescence; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D024510:Muscle Development / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D018482:Muscle, Skeletal / Q000166:cytology*; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D009543:Nifedipine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011840:Radiation, Nonionizing; D044968:Regenerative Medicine / Q000379:methods*; D013194:Staining and Labeling
D000199:Actins; D020746:Calcium Channels, L-Type; D012333:RNA, Messenger; D004247:DNA; D009543:Nifedipine; D002118:Calcium