title: COX-2 inhibitor reduces skeletal muscle hypertrophy in mice.
abstract: Anti-inflammatory strategies are often used to reduce muscle pain and soreness that can result from high-intensity muscular activity. However, studies indicate that components of the acute inflammatory response may be required for muscle repair and growth. The hypothesis of this study was that cyclooxygenase (COX)-2 activity is required for compensatory hypertrophy of skeletal muscle. We used the synergist ablation model of skeletal muscle hypertrophy, along with the specific COX-2 inhibitor NS-398, to investigate the role of COX-2 in overload-induced muscle growth in mice. COX-2 was expressed in plantaris muscles during compensatory hypertrophy and was localized mainly in or near muscle cell nuclei. Treatment with NS-398 blunted the increases in mass and protein content in overloaded muscles compared with vehicle-treated controls. Additionally, the COX-2 inhibitor decreased activity of the urokinase type plasminogen activator, macrophage accumulation, and cell proliferation, all of which are required for hypertrophy after synergist ablation. Expression of insulin-like growth factor-1 and phosphorylation of Akt, mammalian target of rapamycin, and p70S6K were increased following synergist ablation, but were not affected by NS-398. Additionally, expression of atrogin-1 was reduced during hypertrophy, but was also not affected by NS-398. These results demonstrate that COX-2 activity is required for skeletal muscle hypertrophy, possibly through facilitation of extracellular protease activity, macrophage accumulation, and cell proliferation.
authors.affiliation: Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Novak
authors.forename: William
authors.initials: W
authors.lastname: Billich
authors.forename: Sierra M
authors.initials: SM
authors.lastname: Smith
authors.forename: Kunal B
authors.initials: KB
authors.lastname: Sukhija
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: McLoughlin
authors.forename: Troy A
authors.initials: TA
authors.lastname: Hornberger
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Koh
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D006984:Hypertrophy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009135:Muscular Diseases / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D009578:Nitrobenzenes / Q000494:pharmacology*; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D052246:Cyclooxygenase 2 Inhibitors; D009124:Muscle Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D007334:Insulin-Like Growth Factor I; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; D017853:Phosphotransferases (Alcohol Group Acceptor); C546843:mTOR protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D014568:Urokinase-Type Plasminogen Activator