Effect of PARP-1 Inhibition on Rotator Cuff Healing: A Feasibility Study Using Veliparib in a Rat Model of Acute Rotator Cuff Repair.
Publisher DOI
PubMed ID
36745049
Abstract
BACKGROUND
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.
STUDY DESIGN
Controlled laboratory study.
METHODS
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.
RESULTS
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 (P = .034) in the inhibitor group, which was in agreement with an 8.7% higher microscopic muscle fiber diameter on histologic sections (P < .0001). There were no statistically significant differences in the biomechanical properties between the groups.
CONCLUSION
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.
CLINICAL RELEVANCE
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.
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.
STUDY DESIGN
Controlled laboratory study.
METHODS
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.
RESULTS
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 (P = .034) in the inhibitor group, which was in agreement with an 8.7% higher microscopic muscle fiber diameter on histologic sections (P < .0001). There were no statistically significant differences in the biomechanical properties between the groups.
CONCLUSION
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.
CLINICAL RELEVANCE
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.
Date Issued
2023-03
Publication Type
Article
Subject(s)
Subjects
PARP-1 basic science enthesis healing poly-ADP(ribose)polymerase rotator cuff muscle rotator cuff tear
Language(s)
en
Author(s)
McGarry, Michelle H | |
Akeda, Masaki | |
Ihn, Hansel | |
Karol, Agnieszka | |
von Rechenberg, Brigitte | |
Lee, Thay Q |
Additional Credits
Journal
The American journal of sports medicine
Publisher
Sage
ISSN
1552-3365
Access(Rights)
restricted