Effects of Nintedanib on Orofacial Fibroblasts and Myoblasts

Following surgical interventions or acquired trauma, fibrosis often inhibits muscle and skin regeneration. Nintedanib, an antifibrotic drug for lung fibrosis, may help prevent orofacial fibrosis. This study evaluates Nintedanib's potential for inhibiting myofibroblast differentiation and affecting the fusion of orofacial myoblasts into myotubes. Rat gingival fibroblasts and satellite cells (SCs) were isolated and cultured with TGF-β1 to induce myofibroblast differentiation and prevent myotube formation. Adding 1 and 10 ng/mL TGF-β1 significantly increased the percentage of myofibroblasts. Although Nintedanib did not affect the percentage of myofibroblasts, it strongly decreased the total number of fibroblasts and myofibroblasts. Additionally, Nintedanib at a concentration of 2 μM markedly reduced the expression of Ki-67 in fibroblasts and myofibroblasts. In the SC cultures, 0.2 ng/mL TGF-β1 reduced the fusion index of SCs. Treatment with 2 μM Nintedanib significantly increased the fusion index of SCs. Furthermore, MyoD and MyoG gene expression in SCs was also significantly enhanced by Nintedanib at a concentration of 2 μM. Nintedanib promotes myotube formation while inhibiting (myo)fibroblast proliferation. This dual action stresses its potential as an anti-fibrotic therapy after orofacial surgery or traumatic injury affecting muscle tissue.