Künzler Michael B, McGarry Michelle H, Akeda Masaki, Ihn Hansel, Karol Agnieszka, von Rechenberg Brigitte, Schär Michael O, Zumstein Matthias A, Lee Thay Q
Shoulder, Elbow and Orthopaedic Sports Medicine, Inselspital University Hospital Bern, University of Bern, Bern, Switzerland.
Orthopaedics Biomechanics Laboratory, VA Long Beach Healthcare System, Long Beach, California, USA.
Am J Sports Med. 2023 Mar;51(3):758-767. doi: 10.1177/03635465221148494. Epub 2023 Feb 6.
PARP-1 (poly[ADP-ribose]) was shown to influence the inflammatory response after rotator cuff tear, leading to fibrosis, muscular atrophy, and fatty infiltration in mouse rotator cuff degeneration. So far, it is not known how PARP-1 influences enthesis healing after rotator cuff tear repair.
HYPOTHESIS/PURPOSE: This study aimed to examine the feasibility of oral PARP-1 inhibition and investigate its influence on rat supraspinatus enthesis and muscle healing after rotator cuff repair. The hypothesis was that oral PARP-1 inhibition would improve enthesis healing after acute rotator cuff repair in a rat model.
Controlled laboratory study.
In 24 Sprague-Dawley rats, the supraspinatus tendon was sharply detached and immediately repaired with a single transosseous suture. The rats were randomly allocated into 2 groups, with the rats in the inhibitor group receiving veliparib with a target dose of 12.5 mg/kg/d via drinking water during the postoperative recovery period. The animals were sacrificed 8 weeks after surgery. For the analysis, macroscopic, biomechanical, and histologic methods were used.
Oral veliparib was safe for the rats, with no adverse effects observed. In total, the inhibitor group had a significantly better histologic grading of the enthesis with less scar tissue formation. The macroscopic cross-sectional area of the supraspinatus muscles was 10.5% higher ( = .034) in the inhibitor group, which was in agreement with an 8.7% higher microscopic muscle fiber diameter on histologic sections ( < .0001). There were no statistically significant differences in the biomechanical properties between the groups.
This study is the first to investigate the influence of PARP-1 inhibition on healing enthesis. On the basis of these findings, we conclude that oral veliparib, which was previously shown to inhibit PARP-1 effectively, is safe to apply and has beneficial effects on morphologic enthesis healing and muscle fiber size.
Modulating the inflammatory response through PARP-1 inhibition during the postoperative healing period is a promising approach to improve enthesis healing and reduce rotator cuff retearing. With substances already approved by the Food and Drug Administration, PARP-1 inhibition bears high potential for future translation into clinical application.
聚（ADP - 核糖）聚合酶 - 1（PARP - 1）已被证明会影响肩袖撕裂后的炎症反应，导致小鼠肩袖退变出现纤维化、肌肉萎缩和脂肪浸润。到目前为止，尚不清楚PARP - 1如何影响肩袖撕裂修复后的止点愈合。
假设/目的：本研究旨在探讨口服PARP - 1抑制剂的可行性，并研究其对大鼠肩袖修复后冈上肌止点和肌肉愈合的影响。假设是在大鼠模型中，口服PARP - 1抑制剂可改善急性肩袖修复后的止点愈合。
对照实验室研究。
对24只Sprague - Dawley大鼠，锐性切断冈上肌腱并立即用单骨隧道缝线修复。将大鼠随机分为2组，抑制剂组大鼠在术后恢复期通过饮水接受维利帕尼，目标剂量为12.5 mg/kg/d。术后8周处死动物。采用宏观、生物力学和组织学方法进行分析。
口服维利帕尼对大鼠安全，未观察到不良反应。总体而言，抑制剂组止点的组织学分级明显更好，瘢痕组织形成更少。抑制剂组冈上肌的宏观横截面积高10.5%（P = 0.034），这与组织学切片上微观肌纤维直径高8.7%一致（P < 0.0001）。两组之间的生物力学性能无统计学显著差异。
本研究首次探讨了PARP - 1抑制对愈合止点的影响。基于这些发现，我们得出结论，先前已证明能有效抑制PARP - 1的口服维利帕尼应用安全，对止点形态愈合和肌纤维大小有有益影响。
在术后愈合期通过PARP - 1抑制来调节炎症反应是改善止点愈合和减少肩袖再撕裂的一种有前景的方法。利用已获美国食品药品监督管理局批准的物质，PARP - 1抑制在未来转化为临床应用方面具有很大潜力。
