title: Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication.
abstract: 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 ± 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.-Mackey, A. L., Rasmussen, L. K., Kadi, F., Schjerling, P., Helmark, I. C., Ponsot, E., Aagaard, P., Durigan, J. L. Q., Kjaer, M. Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication.
authors.affiliation: Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery M, Bispebjerg Hospital, Copenhagen, Denmark; Department of Biomedical Sciences, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; abigailmac@sund.ku.dk.
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Mackey
authors.affiliation: Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery M, Bispebjerg Hospital, Copenhagen, Denmark;
authors.forename: Lotte K
authors.initials: LK
authors.lastname: Rasmussen
authors.affiliation: School of Health and Medical Sciences, Örebro University, Örebro, Sweden;
authors.forename: Fawzi
authors.initials: F
authors.lastname: Kadi
authors.affiliation: Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery M, Bispebjerg Hospital, Copenhagen, Denmark;
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.affiliation: Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery M, Bispebjerg Hospital, Copenhagen, Denmark;
authors.forename: Ida C
authors.initials: IC
authors.lastname: Helmark
authors.affiliation: School of Health and Medical Sciences, Örebro University, Örebro, Sweden;
authors.forename: Elodie
authors.initials: E
authors.lastname: Ponsot
authors.affiliation: Department of Sports Science and Clinical Biomechanics, Muscle Research Cluster, University of Southern Denmark, Odense, Denmark; and.
authors.forename: Per
authors.initials: P
authors.lastname: Aagaard
authors.affiliation: Physical Therapy Division, University of Brasília, Brasília, Brazil.
authors.forename: João Luiz Q
authors.initials: JL
authors.lastname: Durigan
authors.affiliation: Institute of Sports Medicine Copenhagen, Department of Orthopaedic Surgery M, Bispebjerg Hospital, Copenhagen, Denmark; Department of Biomedical Sciences, Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Michael
authors.initials: M
authors.lastname: Kjaer
mesh_terms: D000293:Adolescent; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001706:Biopsy; D004311:Double-Blind Method; D004558:Electric Stimulation / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects* / Q000502:physiology; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects* / Q000502:physiology; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C497761:NOTCH1 protein, human; D051881:Receptor, Notch1; D012313:RNA; D007052:Ibuprofen
keywords: Notch signaling pathway; Pax7; electrical stimulation; extracellular matrix; telomere length