2015 ISAKOS Biennial Congress ePoster #309

PARP1 Leads to Regeneration and Decreased Fatty Infiltration in the Muscle after Artificial Rotator Cuff Tear in a Mouse Model

Michael Künzler, MD, Bern SWITZERLAND
Michael Schär, MD, Bern SWITZERLAND
Katja Nuss, DVM, Zürich SWITZERLAND
Agnieszka Karol, DVM, Zürich SWITZERLAND
Brigitte Von Rechenberg, Prof., DVM, Zürich SWITZERLAND
Matthias A. Zumstein, MD, Bern SWITZERLAND

University of Bern, Bern, SWITZERLAND

FDA Status Not Applicable

Summary: The knock-out of PARP1, a regulatory gene for cellular homeostasis and in the inflammatory cascade, reduces fatty infiltration and leads to regeneration of the muscle in a mouse model of rotator cuff tear.

Rate:

Abstract:

Introduction

Muscular atrophy and fatty infiltration (FI) are irreversible after chronic rotator cuff (RC) tears. PARP1, a DNA damage repair factor, is a key factor in the up-regulation of inflammation, muscle atrophy and FI.

Aim

The aim was to investigate whether absence of PARP1 would lead to less inflammation, muscle atrophy and FI after RC tear in PARP1 knock-out (KO) mice.

Methods

In PARP1 KO and wild type (WT) mice (n=120) the supraspinatus tendon was unilaterally detached and denervated. Animals were sacrificed 1, 6 and 12 weeks postoperative. We compared early inflammation, atrophy, and FI between the supraspinatus of KO and wild-type mice.

Results

In both groups the muscles retracted; however, the WT muscles retracted more than KO muscles. Tenotomy and denervation resulted in a significant loss of muscle mass in both groups compared to the contralateral side 6w after surgery (KO: 62±11% and WT: 52±11%, p=0.04). 12w postoperatively, the muscular mass increased significant more to almost normal in KO group compared to the WT group (14±6% and 42±7% lower muscle mass respectively; p<0.0001). Gene expression levels of inflammatory and muscular atrophy genes 1w as well as adipogenic genes 6w postoperative revealed significantly lower gene expression in KO group compared to WT group.

Conclusion

Our preliminary results show for the first time that PARP1 knock-out results in decreased early inflammation and better muscle regeneration after RC tenotomy. These findings in combination with lower expression of adipogenic genes lead to the conclusion, that PARP1 has a negative influence on the muscle regeneration after RCT.