Effect of PARP-1 Inhibition on Rotator Cuff Healing: A Feasibility Study Using Veliparib in a Rat Model of Acute Rotator Cuff Repair

被引:0
作者
Kuenzler, Michael B. B. [1 ,2 ,3 ,4 ]
McGarry, Michelle H. H. [1 ,5 ]
Akeda, Masaki [1 ]
Ihn, Hansel [1 ]
Karol, Agnieszka [1 ,4 ]
von Rechenberg, Brigitte [1 ,4 ]
Schaer, Michael O. O. [1 ,3 ]
Zumstein, Matthias A. A. [1 ,3 ,6 ]
Lee, Thay Q. Q. [1 ,5 ]
机构
[1] VA Long Beach Healthcare Syst, Orthopaed Biomech Lab, Long Beach, CA USA
[2] Univ Hosp Bern, Inselspital Bern, Freiburgstr, CH-3010 Bern, Switzerland
[3] Univ Bern, Univ Hosp Bern, Inselspital, Elbow & Orthopaed Sports Med, Bern, Switzerland
[4] Univ Zurich, Vetsuisse Fac, Musculoskeletal Res Unit, Zurich, Switzerland
[5] Congress Med Fdn, Orthopaed Biomech Lab, Pasadena, CA USA
[6] Sonnenhof Orthopaed, Elbow & Orthopaed Sports Med, Bern, Switzerland
关键词
PARP-1; rotator cuff tear; enthesis healing; poly-ADP(ribose)polymerase; rotator cuff muscle; basic science; SUPRASPINATUS MUSCLE; LIPID-ACCUMULATION; REDUCES FIBROSIS; BONE; EXPRESSION; DEGENERATION; ABT-888; ATROPHY; FORCE; AGE;
D O I
10.1177/03635465221148494
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
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.
引用
收藏
页码:758 / 767
页数:10
相关论文
共 37 条
  • [1] The role of loading in murine models of rotator cuff disease
    Abraham, Adam C.
    Fang, Fei
    Golman, Mikhail
    Oikonomou, Panagiotis
    Thomopoulos, Stavros
    [J]. JOURNAL OF ORTHOPAEDIC RESEARCH, 2022, 40 (04) : 977 - 986
  • [2] Targeting the NF-κB signaling pathway in chronic tendon disease
    Abraham, Adam C.
    Shah, Shivam A.
    Golman, Mikhail
    Song, Lee
    Li, Xiaoning
    Kurtaliaj, Iden
    Akbar, Moeed
    Millar, Neal L.
    Abu-Amer, Yousef
    Galatz, Leesa M.
    Thomopoulos, Stavros
    [J]. SCIENCE TRANSLATIONAL MEDICINE, 2019, 11 (481)
  • [3] Effect of Diet-Induced Vitamin D Deficiency on Rotator Cuff Healing in a Rat Model
    Angeline, Michael E.
    Ma, Richard
    Pascual-Garrido, Cecilia
    Voigt, Clifford
    Deng, Xiang Hua
    Warren, Russell F.
    Rodeo, Scott A.
    [J]. AMERICAN JOURNAL OF SPORTS MEDICINE, 2014, 42 (01) : 27 - 34
  • [4] Apostolakos John, 2014, Muscles Ligaments Tendons J, V4, P333
  • [5] Rat supraspinatus muscle atrophy after tendon detachment
    Barton, ER
    Gimbel, JA
    Williams, GR
    Soslowsky, LJ
    [J]. JOURNAL OF ORTHOPAEDIC RESEARCH, 2005, 23 (02) : 259 - 265
  • [6] Rat rotator cuff tendon-to-bone healing properties are adversely affected by hypercholesterolemia
    Beason, David P.
    Tucker, Jennica J.
    Lee, Chang Soo
    Edelstein, Lena
    Abboud, Joseph A.
    Soslowsky, Louis J.
    [J]. JOURNAL OF SHOULDER AND ELBOW SURGERY, 2014, 23 (06) : 867 - 872
  • [7] The effect of matrix metalloproteinase inhibition on tendon-to-bone healing in a rotator cuff repair model
    Bedi, Asheesh
    Kovacevic, David
    Hettrich, Carolyn
    Gulotta, Lawrence V.
    Ehteshami, John R.
    Warren, Russell F.
    Rodeo, Scott A.
    [J]. JOURNAL OF SHOULDER AND ELBOW SURGERY, 2010, 19 (03) : 384 - 391
  • [8] BENJAMIN M, 1986, J ANAT, V149, P89
  • [9] TGF-β Small Molecule Inhibitor SB431542 Reduces Rotator Cuff Muscle Fibrosis and Fatty Infiltration By Promoting Fibro/Adipogenic Progenitor Apoptosis
    Davies, Michael R.
    Liu, Xuhui
    Lee, Lawrence
    Laron, Dominique
    Ning, Anne Y.
    Kim, Hubert T.
    Feeley, Brian T.
    [J]. PLOS ONE, 2016, 11 (05):
  • [10] Simvastatin reduces fibrosis and protects against muscle weakness after massive rotator cuff tear
    Davis, Max E.
    Korn, Michael A.
    Gumucio, Jonathan P.
    Harning, Julie A.
    Saripalli, Anjali L.
    Bedi, Asheesh
    Mendias, Christopher L.
    [J]. JOURNAL OF SHOULDER AND ELBOW SURGERY, 2015, 24 (02) : 280 - 287