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

• Published in: Journal of shoulder and elbow surgery 2017-05, Vol.26 (5), p.733-744
• Main Authors: Kuenzler, Michael B., MD, Nuss, Katja, DVM, Karol, Agnieszka, DVM, Schär, Michael O., MD, Hottiger, Michael, DVM, PhD, Raniga, Sumit, MBChB, FRACS, Kenkel, David, MD, von Rechenberg, Brigitte, DVM, ECVS, Zumstein, Matthias A., MD
• Format: Article
• Language: English
• Subjects: Adipose Tissue - pathology; Animals; ARTD1; Disease Models, Animal; fatty infiltration; inflammation; knock out mouse model; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; muscle atrophy; Muscular Atrophy - diagnostic imaging; Muscular Atrophy - etiology; Muscular Atrophy - pathology; Orthopedics; PARP-1; Poly(ADP-ribose) Polymerases - physiology; Rotator Cuff Injuries - diagnostic imaging; Rotator Cuff Injuries - etiology; Rotator Cuff Injuries - pathology; Rotator cuff tear; supraspinatus muscle; Tenotomy
• ISSN: 1058-2746; 1532-6500
• DOI: 10.1016/j.jse.2016.11.009

Background Disturbed muscular architecture, atrophy, and fatty infiltration remain irreversible in chronic rotator cuff tears even after repair. Poly (adenosine 5′-diphosphate-ribose) polymerase 1 (PARP-1) is a key regulator of inflammation, apoptosis, muscle atrophy, muscle regeneration, and adipocyte development. We hypothesized that the absence of PARP-1 would lead to a reduction in damage to the muscle subsequent to combined tenotomy and neurectomy in a PARP-1 knockout (KO) mouse model. Methods PARP-1 KO and wild-type C57BL/6 (WT group) mice were analyzed at 1, 6, and 12 weeks (total n = 84). In all mice, the supraspinatus and infraspinatus muscles of the left shoulder were detached and denervated. Macroscopic analysis, magnetic resonance imaging, gene expression analysis, immunohistochemistry, and histology were used to assess the differences in PARP-1 KO and WT mice. Results The muscles in the PARP-1 KO group had significantly less retraction, atrophy, and fatty infiltration after 12 weeks than in the WT group. Gene expression of inflammatory, apoptotic, adipogenic, and muscular atrophy genes was significantly decreased in PARP-1 KO mice in the first 6 weeks. Discussion 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.