Molecular mechanism of fatty degeneration in rotator cuff muscle with tendon rupture.
Fatty degeneration often occurs in rotator cuff muscle with tendon rupture. However, the molecular mechanism underlying this change has not been fully clarified yet. We investigated the gene expression of Wnt10b and adipogenic marker gene, PPARγ and C/EBPα in C2C12 myogenic cell line under inhibition of Wnt10b by adipogenic induction medium, isobutylmethylxanthine, dexamethasone, and insulin (MDI). The role of Wnt-signal was confirmed by adding Lithium chloride (LiCl), which mimics Wnt signaling to the cultured cell with MDI. We also assessed the expression profiles of same genes in the rat rotator cuff tear model in vivo. MDI induced Oil red-O staining positive adipocytes and upregulated PPARγ and C/EBPα expression. LiCl inhibited adipogenic induction of MDI. Rotator cuff muscle with tendon rupture showed positive staining for Oil red-O. Real-time polymerase chain reaction analyses revealed decreased expression of Wnt10b followed by increased PPARγ and C/EBPα gene expression in the supraspinatus muscle. Fatty degeneration and its molecular events were remarkably seen in the distal one-third of the detached supraspinatus muscle versus control. Wnt signaling may regulate adipogenic differentiation both in the myoblasts in vitro and the muscle in vivo. Our results indicate that the reduction of Wnt10b in muscle with a rotator cuff tear is a key signal in fatty degeneration of the muscle.
Tohoku University School of Medicine, Sendai, Japan.
Yoshiaki
Y
Itoigawa
Koshi N
KN
Kishimoto
Hirotaka
H
Sano
Kazuo
K
Kaneko
Eiji
E
Itoi
D050156:Adipogenesis; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D002460:Cell Line; D020869:Gene Expression Profiling; D018021:Lithium Chloride; D051379:Mice; D009133:Muscular Atrophy / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017006:Rotator Cuff / Q000378:metabolism / Q000473:pathology; D000070636:Rotator Cuff Injuries; D013708:Tendon Injuries / Q000378:metabolism* / Q000473:pathology; D051153:Wnt Proteins / Q000378:metabolism*
D022763:CCAAT-Enhancer-Binding Protein-alpha; D047495:PPAR gamma; D051153:Wnt Proteins; C102068:Wnt10b protein, mouse; C501228:Wnt10b protein, rat; D018021:Lithium Chloride