Scientific publications

HDACi vorinostat protects muscle from degeneration after acute rotator cuff injury in mice

Apr 15, 2024 | Magazine: Bone Joint Research

Lara Gil-Melgosa  1 , Rafael Llombart-Blanco  1 , Leire Extramiana  2 , Isabel Lacave  3 , Gloria Abizanda  2 , Estibaliz Miranda  4 , Xabier Agirre  4 , Felipe Prósper  4   5   6 , Antonio Pineda-Lucena  7 , Juan Pons-Villanueva  1 , Ana Pérez-Ruiz  2

Aims: Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells.

Methods: HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential.

Results: Vorinostat, a HDACi compound, blocked the adipogenic transformation of muscle-associated FAPs in culture, promoting myogenic progression of the satellite cells. Furthermore, it protected muscle from degeneration after acute RC in mice in the earlier muscle degenerative stage after tenotomy.

Conclusion: The HDACi vorinostat may be a candidate to prevent early muscular degeneration after RC injury.

CITATION  Bone Joint Res. 2024 Apr 15;13(4):169-183. doi: 10.1302/2046-3758.134.BJR-2023-0292.R1