Neer Award 2016: reduced muscle degeneration and decreased fatty infiltration after rotator cuff tear in a poly(ADP-ribose) polymerase 1 (PARP-1) knock-out mouse model

Abstract

Absence of PARP-1 leads to a reduction in muscular architectural damage, early inflammation, apoptosis, atrophy, and fatty infiltration after combined tenotomy and neurectomy of the rotator cuff muscle. Although the macroscopic reaction to injury is similar in the first 6 weeks, the ability of the muscles to regenerate was much greater in the PARP-1 KO group, leading to a near-normalization of the muscle after 12 weeks.

Biologics and stem cell‐based therapies for rotator cuff repair

“…Although the majority of rodent rotator cuff studies have been carried out in rat, the mouse shoulder anatomy was recently shown to be comparable to rat and human. The very small size of the mouse rotator cuff precluded its use in earlier studies; however, novel microsurgical techniques have now been applied to successfully create partial and full detachment injuries with surgical repair, thereby opening new avenues for mechanistic research . Despite the numerous advantages of rat models, limitations include scar‐mediated healing (human tears do not undergo spontaneous healing), quadrupedal gait, and small scale relative to human .…”

“…Therefore, the majority of studies for rotator cuff tendon tears employ an acute laceration injury of otherwise healthy tendon. These models include detachment of the supraspinatus tendon, either alone or in tandem with the infraspinatus or other tendons, to model massive rotator cuff tears . Reattachment surgeries are typically carried out immediately after detachment, and overall healing evaluated at later timepoints .…”

“…Prolonged unloading resulted in tendon retraction, muscle atrophy, fatty infiltration, and fibrotic scarring. Despite eventual repair, these studies generally suggested that the pathological events associated with unloading cannot be reversed by simple reattachment …”

“…The very small size of the mouse rotator cuff precluded its use in earlier studies; however, novel microsurgical techniques have now been applied to successfully create partial and full detachment injuries with surgical repair, thereby opening new avenues for mechanistic research. [18][19][20][21][22][23][24] Despite the numerous advantages of rat models, limitations include scar-mediated healing (human tears do not undergo spontaneous healing), quadrupedal gait, and small scale relative to human. 17 While joint replacement or other medical devices cannot be tested in rodent models, preclinical studies testing the efficacy of cell and biomolecule-based therapies are acceptable in rodents for meeting FDA standards.…”

“…These models include detachment of the supraspinatus tendon, either alone or in tandem with the infraspinatus or other tendons, to model massive rotator cuff tears. [18][19][20]33,34 Reattachment surgeries are typically carried out immediately after detachment, and overall healing evaluated at later timepoints. 21,22,[35][36][37][38][39][40][41] Because the laceration injuries and repairs are quite invasive, the environment after injury differs in significant ways from degenerationinduced tears observed in the clinic.…”