TY - JOUR
T1 - Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication
AU - Mackey, Abigail L
AU - Rasmussen, Lotte Klejs
AU - Kadi, Fawzi
AU - Schjerling, Peter
AU - Helmark, Ida C
AU - Ponsot, Elodie
AU - Aagaard, Per
AU - Durigan, João Luiz Q
AU - Kjaer, Michael
N1 - © FASEB.
PY - 2016/6
Y1 - 2016/6
N2 - With this study we investigated the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in human skeletal muscle regeneration. Young men ingested NSAID [1200 mg/d ibuprofen (IBU)] or placebo (PLA) daily for 2 wk before and 4 wk after an electrical stimulation-induced injury to the leg extensor muscles of one leg. Muscle biopsies were collected from the vastus lateralis muscles before and after stimulation (2.5 h and 2, 7, and 30 d) and were assessed for satellite cells and regeneration by immunohistochemistry and real-time RT-PCR, and we also measured telomere length. After injury, and compared with PLA, IBU was found to augment the proportion of ActiveNotch1+ satellite cells at 2 d [IBU, 29 ± 3% vs. PLA, 19 6 2% (means ± SEM)], satellite cell content at 7 d [IBU, 0.16 ± 0.01 vs. PLA, 0.12 ± 0.01 (Pax7+ cells/fiber)], and to expedite muscle repair at 30 d. The PLA group displayed a greater proportion of embryonic myosin+ fibers and a residual ∼2-fold increase in mRNA levels of matrix proteins (all P < 0.05). Endomysial collagen was also elevated with PLA at 30 d. Minimum telomere length shortening was not observed. In conclusion, ingestion of NSAID has a potentiating effect on Notch activation of satellite cells and muscle remodeling during large-scale regeneration of injured human skeletal muscle.
AB - With this study we investigated the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in human skeletal muscle regeneration. Young men ingested NSAID [1200 mg/d ibuprofen (IBU)] or placebo (PLA) daily for 2 wk before and 4 wk after an electrical stimulation-induced injury to the leg extensor muscles of one leg. Muscle biopsies were collected from the vastus lateralis muscles before and after stimulation (2.5 h and 2, 7, and 30 d) and were assessed for satellite cells and regeneration by immunohistochemistry and real-time RT-PCR, and we also measured telomere length. After injury, and compared with PLA, IBU was found to augment the proportion of ActiveNotch1+ satellite cells at 2 d [IBU, 29 ± 3% vs. PLA, 19 6 2% (means ± SEM)], satellite cell content at 7 d [IBU, 0.16 ± 0.01 vs. PLA, 0.12 ± 0.01 (Pax7+ cells/fiber)], and to expedite muscle repair at 30 d. The PLA group displayed a greater proportion of embryonic myosin+ fibers and a residual ∼2-fold increase in mRNA levels of matrix proteins (all P < 0.05). Endomysial collagen was also elevated with PLA at 30 d. Minimum telomere length shortening was not observed. In conclusion, ingestion of NSAID has a potentiating effect on Notch activation of satellite cells and muscle remodeling during large-scale regeneration of injured human skeletal muscle.
U2 - 10.1096/fj.201500198r
DO - 10.1096/fj.201500198r
M3 - Journal article
C2 - 26936358
SN - 0892-6638
VL - 30
SP - 2266
EP - 2281
JO - FASEB journal : official publication of the Federation of American Societies for Experimental Biology
JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology
IS - 6
ER -