Possible involvement of IGF-1 signaling on compensatory growth of the infraspinatus muscle induced by the supraspinatus tendon detachment of rat shoulder

Abstract

A rotator cuff tear (RCT) is a common musculoskeletal disorder among elderly people. RCT is often treated conservatively for functional compensation by the remaining muscles. However, the mode of such compensation after RCT has not yet been fully understood. Here, we used the RCT rat model to investigate the compensatory process in the remaining muscles. The involvement of insulin‐like growth factor 1 (IGF‐1)/Akt signaling which potentially contributes to the muscle growth was also examined. The RCT made by transecting the supraspinatus (SSP) tendon resulted in atrophy of the SSP muscle. The remaining infraspinatus (ISP) muscle weight increased rapidly after a transient decrease (3 days), which could be induced by posttraumatic immobilization. The IGF‐1 mRNA levels increased transiently at 7 days followed by a gradual increase thereafter in the ISP muscle, and those of IGF‐1 receptor mRNA significantly increased after 3 days. IGF‐1 protein levels biphasically increased (3 and 14 days), then gradually decreased thereafter. The IGF‐1 protein levels tended to show a negative correlation with IGF‐1 mRNA levels. These levels also showed a negative correlation with the ISP muscle weight, indicating that the increase in IGF‐1 secretion may contribute to the ISP muscle growth. The pAkt/Akt protein ratio decreased transiently by 14 days, but recovered later. The IGF‐1 protein levels were negatively correlated with the pAkt/Akt ratio. These results indicate that transection of the SSP tendon activates IGF‐1/Akt signaling in the remaining ISP muscle for structural compensation. Thus, the remaining muscles after RCT can be a target for rehabilitation through the activation of IGF‐1/Akt signaling.

Compensatory hypertrophy of the teres minor muscle after large rotator cuff tear model in adult male rat

“…Under general anesthesia with ketamine (60 mg/kg body weight) and xylazine (12 mg/kg body weight, intraperitoneally), all rats underwent transection of the SSN and the SSP and ISP tendons of the left shoulder partially according to previous reports. 11,16,21 The right shoulder was left intact as a control. A 2-cm skin incision was made at the lateral aspect of the shoulder, and the underlying deltoid muscle was dissected bluntly along the muscle fiber to expose the rotator cuff tendons.…”

“…The sample dilution, heat-denaturation, polyacrylamide gel electrophoresis, blotting to a nitrocellulose membrane, blocking, antibody reaction, and imaging were performed as previously described. 11 The amount of loaded sample was 50 mg/lane, and the concentration of polyacrylamide gel used in this study was 7.5%. Primary antibodies and the dilution ranges were rabbit monoclonal anti- Akt (1:2000), anti-p-Akt (ser473, 1:2000), anti-mTOR (1:2000), or anti-p-TOR (1:500) antibodies (all from Cell Signaling Technology Inc, Danvers, MA, USA).…”

“…Similar to the protocol of our previous study, 11 protein samples from the TM muscle were prepared, and the total protein concentrations were determined. The samples were stored at À80 C until use.…”

“…We set this time point in accordance with our previous results that morphologic and molecular changes become evident within 4 weeks after surgery. 11 The deltoid muscle was removed carefully without injuring the rotator cuff tendons. The SSP, ISP, and TM muscles of both forelimbs were removed from the scapula and humerus.…”

“…5,25 However, a human study reported that the remaining TM muscle becomes hypertrophic when the RCT extends to the ISP tendon, 13 and we have reported the possibility of compensatory hypertrophy of the ISP muscle in a RCT rat model. 11 The Akt (protein kinase B) and mammalian target of rapamycin (mTOR) signaling pathways are important in the growth and hypertrophy of skeletal muscle. Akt acts as a critical signaling component for the regulation of various cellular functions.…”