Prolonged tadalafil exposure promotes skeletal muscle myogenesis and regulates early myogenic markers activation in C2C12 cell lines.

purposeThe regeneration of skeletal muscle depends on the activation and differentiation of myogenic progenitor cells. Tadalafil, one of the phosphodiesterase type 5 inhibitors, is known to modulate nitric oxide/cGMP signaling; however, its prolonged effects on myogenic progression are not well understood. This study investigates the impact of prolonged tadalafil exposure on C2C12 myoblasts and early myogenic progenitor markers activation.

methodsC2C12 cells were treated with 1 µM tadalafil for up to seven days, and analyzed for proliferation, viability, myogenesis activation and myokine release.

resultsProlonged tadalafil treatment significantly increased cell proliferation and survival, reducing cell death at all time points. Although tadalafil enhanced the expression of early myogenic factors, it simultaneously delayed terminal differentiation, reducing MHC-positive multinucleated myotubes, while maintaining higher expression levels of Pax7 and Myf6 after seven days, consistent with a less differentiated phenotype. This result was accompanied by the upregulation of Sirt3 and IL6, and the downregulation of myostatin and TGFβ.

conclusionsTadalafil promoted a highly proliferative state and preventing premature differentiation. These findings suggest its potential use as an adjuvant pharmacological therapy in the treatment of muscle-wasting disorders. However, the potent improvement of muscle regenerative machinery raises critical concerns regarding its potential misuse as a performance-enhancing drug in sport, highlighting the need for evaluation by anti-doping agencies.