Disturbed muscular architecture, fatty infiltration and muscular atrophy remain irreversible in chronic rotator cuff tears (RCT) even after repair. Poly-[ADP-ribose]-polymerase 1 (PARP-1), a nuclear factor involved in DNA damage repair, has shown to be a key element in the up-regulation of early muscle inflammation, atrophy and fat deposition. We therefore hypothesized that the absence of PARP-1 would lead to a reduction in muscular architectural damage, early inflammation, atrophy and fatty infiltration subsequent to combined tenotomy and neurectomy in a PARP-1 knock-out mouse model.

PARP-1 knock-out (KO group) and standard wild type C57BL/6 (WT group) mice were randomly allocated into three different time points (1, 6 and 12 weeks, total n=72). In all mice the supraspinatus (SSP) and infraspinatus (ISP) tendons of the left shoulder were detached and the SSP muscle was denervated according to a recently established model. Macroscopic muscle weight analysis, retraction documentation using macroscopic suture, magnetic resonance imaging, immunohistochemistry gene expression analysis using real time qPCR (RTqPCR) and histology were used to assess the differences in muscle architecture, early inflammation, fatty infiltration and atrophy between knock out and wild type mice in the supraspinatus muscle.

The SSP did retract in both groups, however; the KO muscles and tendons retracted less than the WT muscles (2.1±21mm vs 3.4±0.41mm; p=0.02). Further assessment of muscle architecture demonstrated that the pennation angle was significantly higher in the KO groups at 6 and 12 weeks (28±5 vs 36±5 and 29±4 vs 34±3; p<0.0001). Combined Tenotomy and neurectomy resulted in a significant loss of muscle mass in both groups compared to the contralateral unoperated side (KO group 62±11% and WT group 52±11%, p=0.04) at 6 weeks. But at 12 weeks postoperatively, there was a significant increase in muscle mass to near normal levels in KO group compared to the WT group (14±6% and 42±7% lower muscle mass respectively; p<0.0001) and less fatty infiltration (12.5 ± 1.82% and 19.6 ± 1.96%, p=0.027). Immunohistochemistry revealed a significant decrease in the expression of inflammatory, apoptotic, adipogenic and muscular atrophy genes at both the 1 week and 6 weeks time points, but not at 12 weeks in the KO group compared to the WT group. This was confirmed by histology.

Our study is the first to show that knocking out PARP-1 leads to decreased loss of muscle architecture, early inflammation, fatty infiltration and atrophy after combined tenotomy and neurectomy of the rotator cuff muscle. Although the macroscopic muscles reaction to injury is similar in the first 6 weeks, its ability to regenerate is much greater in the PARP-1 group leading to a near normalization of the muscle substance and muscle weight, less retraction, and less fatty infiltration after 12 weeks.

Summary

Nasal Chondrocytes are safe and feasible for tissue engineering approaches in articular cartilage repair.

We released the infraspinatus tendons of six sheep, allowed retraction of the musculotendinous unit over a period of 40 weeks and then performed a repair. We studied retraction of the musculotendinous unit 35 weeks later using CT, MRI and macroscopic dissection.

The tendon was retracted by a mean of 4.7 cm (3.8 to 5.1) 40 weeks after release and remained at a mean of 4.2 cm (3.3 to 4.7) 35 weeks after the repair. Retraction of the muscle was only a mean of 2.7 cm (2.0 to 3.3) and 1.7 cm (1.1 to 2.2) respectively at these two points. Thus, the musculotendinous junction had shifted distally by a mean of 2.5 cm (2.0 to 2.8) relative to the tendon. Sheep muscle showed an ability to compensate for approximately 60% of the tendon retraction in a hitherto unknown fashion. Such retraction may not be a quantitatively reliable indicator of retraction of the muscle and may overestimate the need for elongation of the musculotendinous unit during repair.