# Effects of Nintedanib on Orofacial Fibroblasts and Myoblasts

**Authors:** Zhihao Wang, Frank A. D. T. G. Wagener, Edwin M. Ongkosuwito, Johannes W. Von den Hoff

PMC · DOI: 10.3390/biom16020316 · Biomolecules · 2026-02-18

## TL;DR

Nintedanib may help reduce fibrosis and improve muscle regeneration in orofacial injuries by inhibiting fibroblast proliferation and promoting muscle cell fusion.

## Contribution

The study reveals Nintedanib's dual effect on inhibiting fibroblast proliferation and enhancing myoblast fusion in orofacial tissues.

## Key findings

- Nintedanib reduced fibroblast and myofibroblast numbers but did not affect myofibroblast percentage.
- Nintedanib increased myoblast fusion and enhanced MyoD and MyoG gene expression.
- Nintedanib shows potential as an anti-fibrotic therapy for orofacial muscle tissue regeneration.

## Abstract

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.

## Linked entities

- **Genes:** MYOD1 (myogenic differentiation 1) [NCBI Gene 4654], MYOG (myogenin) [NCBI Gene 4656]
- **Proteins:** TGFB1 (transforming growth factor beta 1), Mki67 (antigen identified by monoclonal antibody Ki 67)
- **Chemicals:** Nintedanib (PubChem CID 135423438)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, ACTA1 (actin alpha 1, skeletal muscle) [NCBI Gene 58] {aka ACTA, ASMA, CFTD, CFTD1, CFTDM, CMYO2A}, MSTN (myostatin) [NCBI Gene 2660] {aka GDF8, MSLHP}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, FAP (fibroblast activation protein alpha) [NCBI Gene 2191] {aka DPPIV, FAPA, FAPalpha, SIMP}, ACTA2 (actin alpha 2, smooth muscle) [NCBI Gene 59] {aka ACTSA, SMDYS}, TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, MYH6 (myosin heavy chain 6) [NCBI Gene 4624] {aka ASD3, CMD1EE, CMH14, MYHC, MYHCA, SSS3}, TBK1 (TANK binding kinase 1) [NCBI Gene 29110] {aka AIARV, FTDALS4, IIAE8, NAK, T2K}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, Myog (myogenin) [NCBI Gene 29148], TGFBR2 (transforming growth factor beta receptor 2) [NCBI Gene 7048] {aka AAT3, FAA3, LDS1B, LDS2, LDS2B, MFS2}, KDR (kinase insert domain receptor) [NCBI Gene 3791] {aka CD309, FLK1, VEGFR, VEGFR2}, MyHC [NCBI Gene 29605], DUSP5 (dual specificity phosphatase 5) [NCBI Gene 1847] {aka DUSP, HVH3}, TGFBR1 (transforming growth factor beta receptor 1) [NCBI Gene 7046] {aka AAT5, ACVRLK4, ALK-5, ALK5, ESS1, LDS1}, PDGFRA (platelet derived growth factor receptor alpha) [NCBI Gene 5156] {aka CD140A, PDGFR-2, PDGFR2}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, SMAD3 (SMAD family member 3) [NCBI Gene 4088] {aka HSPC193, HsT17436, JV15-2, LDS1C, LDS3, MADH3}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, ACAT2 (acetyl-CoA acetyltransferase 2) [NCBI Gene 39], MYH14 (myosin heavy chain 14) [NCBI Gene 79784] {aka DFNA4, DFNA4A, FP17425, MHC16, MYH17, NMHC II-C}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, PDGFRB (platelet derived growth factor receptor beta) [NCBI Gene 5159] {aka CD140B, IBGC4, IMF1, JTK12, KOGS, OPDKD}, Pax7 (paired box 7) [NCBI Gene 18509] {aka Pax-7}, PAX7 (paired box 7) [NCBI Gene 5081] {aka CMYO19, CMYP19, HUP1, MYOSCO, PAX7B, RMS2}, MYOG (myogenin) [NCBI Gene 4656] {aka MYF4, bHLHc3, myf-4}, Myhc (myosin heavy chain, cardiac muscle complex) [NCBI Gene 111671], COL1A1 (collagen type I alpha 1 chain) [NCBI Gene 1277] {aka CAFYD, EDSARTH1, EDSC, OI1, OI2, OI3}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, MYOD1 (myogenic differentiation 1) [NCBI Gene 4654] {aka CMYO17, CMYP17, MYF3, MYOD, MYODRIF, PUM}
- **Diseases:** systemic sclerosis (MESH:D012595), function (MESH:D003291), hereditary hemorrhagic telangiectasia (MESH:D013683), Fibrosis (MESH:D005355), inflammation (MESH:D007249), Injury (MESH:D014947), fibrotic diseases (MESH:D004194), muscle (MESH:D019042), muscular dystrophy (MESH:D009136), heart failure (MESH:D006333), ILD (MESH:D017563), Muscle injury (MESH:D009135), keloid (MESH:D007627), soft palate (MESH:C562950), cleft palate (MESH:D002972), IPF (MESH:D054990), sarcoglycanopathies (MESH:D058088), cleft (MESH:D002971)
- **Chemicals:** HA (MESH:D006820), glycine (MESH:D005998), water (MESH:D014867), TBS (MESH:D013725), Trizol (MESH:C411644), streptomycin (MESH:D013307), Triton X-100 (MESH:D017830), SB203580 (MESH:C093642), saline (MESH:D012965), SCM (MESH:D000198), calcein-AM (MESH:C085925), DABCO (MESH:C007306), PBS (MESH:D007854), Tween-20 (MESH:D011136), ice (MESH:D007053), Nintedanib (MESH:C530716), 4',6-diamidino-2-phenylindole (MESH:C007293), DMSO (MESH:D004121), formaldehyde (MESH:D005557), SB 431542 (MESH:C459179), paraformaldehyde (MESH:C003043), Pirfenidone (MESH:C093844), U0126 (MESH:C113580), Alexa Fluor 488 (MESH:C000711379), creatine (MESH:D003401), DMEM (-), Alexa Fluor 647 (MESH:C569686), penicillin (MESH:D010406), ethidium homodimer-1 (MESH:C018533)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** C2C12 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0188), fibroblasts — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938516/full.md

## References

73 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938516/full.md

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Source: https://tomesphere.com/paper/PMC12938516