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, PPAR gamma and C / EBP alpha 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 PPAR gamma and C / EBP alpha 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 WntlOb followed by increased PPAR gamma and C / EBP alpha 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. (C) 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:861-866, 2011