Costamere protein expression and tissue composition of rotator cuff muscle after tendon release in sheep

Abstract

Previous studies suggested that degradation of contractile tissue requires cleavage of the costamere, a structural protein complex that holds sarcomeres in place. This study examined if costamere turnover is affected by a rotator cuff tear in a previously established ovine model. We found the activity of focal adhesion kinase (FAK), a main regulator of costamere turnover, was unchanged at 2 weeks but decreased by 27% 16 weeks after surgical release of the infraspinatus tendon. This was accompanied by cleavage of the costamere protein talin into a 190 kDa fragment while full length talin remained unchanged. At 2 weeks after tendon release, muscle volume decreased by 17 cm3 from an initial 185 cm3, the fatty tissue volume was halved, and the contractile tissue volume remained unchanged. After 16 weeks, the muscle volume decreased by 36 cm3, contractile tissue was quantitatively lost, and the fat content increased by 184%. Nandrolone administration mitigated the loss of contractile tissue by 26% and prevented fat accumulation, alterations in FAK activity, and talin cleavage. Taken together, these findings imply that muscle remodeling after tendon release occurs in two stages. The early decrease of muscle volume is associated with reduction of fat; while, the second stage is characterized by substantial loss of contractile tissue accompanied by massive fat accumulation. Regulation of costamere turnover is associated with the loss of contractile tissue and seems to be impacted by nandrolone treatment. Clinically, the costamere may represent a potential intervention target to mitigate muscle loss after a rotator cuff tear. © 2017 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 36:272–281, 2018.

Regional regulation of focal adhesion kinase after concentric and eccentric loading is related to remodelling of human skeletal muscle

“…Specific Y397‐phosphorylation of FAK was calculated as the ratio between pY397‐FAK levels and total FAK levels. FAK‐pY397 and total FAK were detected using a home‐made polyclonal rabbit a‐FAK serum (1:1,000) as described previously, gamma‐ and meta‐vinculin were detected using a mouse a‐vinculin serum (gift of Dr. M. A. Glukhova, Paris, France; 1:100), whereas fast myosin was detected using a mouse a‐skeletal myosin (fast) (M4276, Sigma‐Aldrich), as previously described . Then, the Goat a‐mouse antibody #A9917 (Sigma‐Aldrich) secondary antibody (1:20 000) was applied on the respective membranes.…”

Knee Extensors Muscle Plasticity Over a 5-Years Rehabilitation Process After Open Knee Surgery

“…Levels of molecular regulators of the myogenic (myoD, myoG) and metabolic phenotype (respiratory complex I-V, tenascin-C, VEGF), and actin, were determined in total homogenate after separation of proteins by SDS/PAGE and immunoblotting and signal detection with enhanced chemoluminescence essentially as described ( Frese et al, 2016 ; Ruoss et al, 2017 ). The primary antibodies used are provided in Table 1 .…”

Inhibition of calpain delays early muscle atrophy after rotator cuff tendon release in sheep

“…; Ruoss et al. ) are comparable to changes observed in human RC muscles, as opposed to small animal models, which do not present these features (Lebaschi et al. ; Rui et al.…”

“…; Ruoss et al. ). Loss of contractile tissue leads to both radial and longitudinal atrophy, the latter leading to the clinical phenomenon of “myotendinous retraction” which is related to serial removal of sarcomeres from myofibrils (Jamali et al.…”

“…, ; Ruoss et al. ). Thus, successful prevention of early adaptations to tear‐induced unloading could extend the window of opportunity for successful surgical repair and recovery of muscle function.…”