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J Shoulder Elbow Surg. 2017 May;26(5):733-744. doi: 10.1016/j.jse.2016.11.009. Epub 2017 Jan 25.

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.

Author information

1
Shoulder, Elbow and Orthopaedic Sports Medicine, Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Musculoskeletal Research Unit (MSRU), Equine Department, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
2
Musculoskeletal Research Unit (MSRU), Equine Department, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
3
Shoulder, Elbow and Orthopaedic Sports Medicine, Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
4
Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Zürich, Switzerland; Competence Center for Applied Biotechnology and Molecular Medicine (CABMM), Equine Department, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
5
Department of Diagnostic and Interventional Radiology, University Hospital of Zürich, Zürich, Switzerland.
6
Musculoskeletal Research Unit (MSRU), Equine Department, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland; Competence Center for Applied Biotechnology and Molecular Medicine (CABMM), Equine Department, Vetsuisse Faculty, University of Zürich, Zürich, Switzerland.
7
Shoulder, Elbow and Orthopaedic Sports Medicine, Department of Orthopaedic Surgery and Traumatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Shoulder & Elbow Unit, SportsClinic #1 AG, Bern, Switzerland. Electronic address: m.zumstein@me.com.

Abstract

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.

KEYWORDS:

ARTD1; PARP-1; Rotator cuff tear; fatty infiltration; inflammation; knock out mouse model; muscle atrophy; supraspinatus muscle

PMID:
28131694
DOI:
10.1016/j.jse.2016.11.009
[Indexed for MEDLINE]

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