Drug Design, Development and Therapy (Jul 2019)

Effects of losartan and atorvastatin on the development of early posttraumatic joint stiffness in a rat model

  • Baranowski A,
  • Schlemmer L,
  • Förster K,
  • Slotina E,
  • Mickan T,
  • Truffel S,
  • Klein A,
  • Mattyasovszky SG,
  • Hofmann A,
  • Ritz U,
  • Rommens PM

Journal volume & issue
Vol. Volume 13
pp. 2603 – 2618

Abstract

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Andreas Baranowski,1 Ludwig Schlemmer,1 Katharina Förster,1 Ekaterina Slotina,1 Tim Mickan,1 Sebastian Truffel,1 Anja Klein,1 Stefan G Mattyasovszky,1 Alexander Hofmann,1,2 Ulrike Ritz,1 Pol M Rommens11Department of Orthopaedics and Traumatology, Biomatics Group, University Medical Centre of the Johannes Gutenberg University, Mainz, Germany; 2Department of Traumatology and Orthopaedics 1, Westpfalz-Medical Centre Kaiserslautern, Kaiserslautern, GermanyBackground: After a trauma, exuberant tissue healing with fibrosis of the joint capsule can lead to posttraumatic joint stiffness (PTJS). Losartan and atorvastatin have both shown their antifibrotic effects in different organ systems.Objective: The purpose of this study was the evaluation of the influence of losartan and atorvastatin on the early development of joint contracture. In addition to joint angles, the change in myofibroblast numbers and the distribution of bone sialoprotein (BSP) were assessed.Study design and methods: In this randomized and blinded experimental study with 24 rats, losartan and atorvastatin were compared to a placebo. After an initial joint injury, rat knees were immobilized with a Kirschner wire. Rats received either losartan, atorvastatin or a placebo orally daily. After 14 days, joint angle measurements and histological assessments were performed.Results: Losartan increased the length of the inferior joint capsule. Joint angle and other capsule length measurements did not reveal significant differences between both drugs and the placebo. At cellular level both losartan and atorvastatin reduced the total number of myofibroblasts (losartan: 191±77, atorvastatin: 98±58, placebo: 319±113 per counting field, p<0.01) and the percentage area of myofibroblasts (losartan: 2.8±1.8% [p<0.05], atorvastatin: 2.5±1.7% [p<0.01], vs control [6.4±4%], respectively). BSP was detectable in equivalent amounts in the joint capsules of all groups with only a trend toward a reduction of the BSP-stained area by atorvastatin.Conclusion: Both atorvastatin and losartan reduced the number of myofibroblasts in the posterior knee joint capsule of rat knees 2 weeks after trauma and losartan increased the length of the inferior joint capsule. However, these changes at the cellular level did not translate an increase in range of motion of the rats´ knee joints during early contracture development.Keywords: posttraumatic joint stiffness, knee joint contracture, rat model, myofibroblast, antifibrotic drugs, bone sialoprotein

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