Animal models for rotator cuff repair : A review of animal models for musculoskeletal research

Summary Cell growth (accumulation of mass) needs to be coordinated with metabolic processes that are required for the synthesis of macromolecules. The PI3-kinase/Akt signaling pathway induces cell growth via activation of complex 1 of the target of rapamycin (TORC1). Here we show that Akt-dependent lipogenesis requires mTORC1 activity. Furthermore, nuclear accumulation of the mature form of the sterol responsive element binding protein (SREBP1) and expression of SREBP target genes was blocked by the mTORC1 inhibitor rapamycin. We also show that silencing of SREBP blocks Akt-dependent lipogenesis and attenuates the increase in cell size in response to Akt activation in vitro. Silencing of dSREBP in flies caused a reduction in cell and organ size and blocked the induction of cell growth by dPI3K. Our results suggest that the PI3K/Akt/TOR pathway regulates protein and lipid biosynthesis in an orchestrated manner and that both processes are required for cell growth.

The role of degenerative changes in rotator cuff musculature with respect to the functional outcomes of rotator cuff repair have only recently been recognized and are still not well understood. In addition, the reversibility of these changes with repair of the tendons is questionable. Poorer preoperative muscle quality negatively affects outcome, and a successful outcome (in terms of a healed repair) might demonstrate improvements in fatty infiltration and muscle atrophy. Cohort study; Level of evidence, 2. Thirty-eight patients (mean age, 62 years) were prospectively evaluated with preoperative and 1-year postoperative clinical examination and appropriate magnetic resonance image sequencing to determine grades of muscle atrophy and fatty infiltration of the supraspinatus and infraspinatus muscles. American Shoulder and Elbow Society (ASES), Constant, and pain scores were determined as well as strength measurements. The retear rate and progression of muscle degeneration were also evaluated. Independent predictors of outcome measurements and cuff integrity were determined. The overall clinical outcome, including ASES, Constant, and pain scores, improved significantly (P < .0001). Strength in forward elevation improved significantly (P < .006), while external rotation strength did not. There was a strongly negative correlation between muscle quality and outcome results in most cases. When the results were adjusted for multivariate effect, muscle atrophy and fatty infiltration of the infraspinatus muscle were the only independent predictors of ASES and Constant scores (P < .03). Tear size and rotator cuff healing did not play an independent role. Tear size, however, was the only independent predictor of ultimate cuff integrity (P = .002). Both atrophy and fatty infiltration progressed significantly over the course of the study. In cases in which the tendon had re-torn, the progression was found to be more significant than when the repair proved successful (P < .003). Muscle atrophy and fatty infiltration of the rotator cuff muscles, particularly of the infraspinatus, play a significant role in determining functional outcome after cuff repair. Tear size appears to have the most influential effect on repair integrity. A successful repair did not lead to improvement or reversal of muscle degeneration and a failed repair resulted in significantly more progression. In general, healed repairs demonstrated minimal progression. These findings suggest that repairs should be performed, if possible, before more significant deterioration in the cuff musculature in order to optimize outcomes, and that understanding the degree of muscle atrophy and fatty infiltration before surgery can help guide patient expectations.

Twenty-seven patients with twenty-seven involved shoulders underwent a second attempt at repair of an initial rotator-cuff repair that had failed. Factors associated with the failure of the initial repair included a massive or large tendon tear, damage to the deltoid origin at the original surgery, and possibly inadequate postoperative external support. Seven patients required a third operation because of continuing pain or weakness. The remaining twenty patients were followed for a minimum of two years (average, forty-eight months) and seventeen of them were examined at an average of forty-six months (range, twenty-six to 118 months) after surgery. Postoperatively, although seventeen patients (63 per cent) still had moderate or severe pain, sixteen (76 per cent) of the twenty-one patients who were operated on to relieve pain reported that the pain was substantially diminished. Active abduction increased an average of 8 degrees, but only seven shoulders gained more than 30 degrees of active abduction. Nineteen shoulders remained moderately or markedly weak in abduction. Over-all, four patients (17 per cent) had a good result; six (25 per cent), a fair result; and fourteen (58 per cent), a poor result. These results suggest that the surgeon should be quite hesitant to propose a second attempt at rotator cuff repair to a patient, as although pain may be diminished, active movement is unlikely to improve.