Acute molecular biological responses during spontaneous anterior cruciate ligament healing in a rat model

  • Yuri Morishita
  • Naohiko KanemuraEmail author
  • Takanori Kokubun
  • Kenji Murata
  • Kiyomi Takayanagi
Original Article



Anterior cruciate ligament (ACL) injury is one of the most common injuries of the knee joint and is becoming more prevalent. While ACL reconstruction is considered the “gold standard” of treatment, some studies have demonstrated natural spontaneous healing of the ACL in humans, rabbits, and rats. At this time, the mechanism of ACL healing is poorly understood.


The purpose of this study was to determine the process of ACL healing by examining the molecular and histological changes in the acute phases, using an ACL-Transection model and a spontaneous ACL healing model.


Sixty adult male Wistar rats were randomly assigned to two groups: the ACL transection (ACLT) group and the controlled abnormal movement (CAM) group. Thirty rats were randomly assigned to three groups (day 1, day 3, and day 5). Then, all rats underwent an ACL transection procedure. The CAM group rats underwent controlled abnormal extra-articular tibial translation. Samples were harvested from rats and used for histological and biochemical analyses.


Both, the ACLT and the CAM groups exhibited ruptured ACLs. However, in the CAM group, the ends of the proximal remnants were not retracted. Expressions of MMP-3 and PDGF-α increased, and expression of TGF-β1 decreased in the CAM group on day 5 (p < 0.01); PDGF-β expression in the CAM group increased significantly at each time point (p < 0.01).


Our results suggested that controlling abnormal movements changed intra-articular responses positively during the acute phase both histologically and biochemically.


Anterior cruciate ligament Anterior cruciate ligament injury Wound healing Rehabilitation Acute-phase reaction 



Anterior cruciate ligament


Anterior cruciate ligament transection


Controlled abnormal movement


Medial collateral ligament


Post-traumatic osteoarthritis


Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest directly relevant to the contents of this article.

Human and animal rights

This study is an animal experimental study. All experiments were approved by the University Animal Experiment Ethics Committee (authorization number 26-5). In addition, in the actual experiments, the authors undertook to minimize the number of animals and stress on the animals.

Informed consent

Informed consent is not applicable for this type of study.


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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  • Yuri Morishita
    • 1
  • Naohiko Kanemura
    • 2
    Email author
  • Takanori Kokubun
    • 2
  • Kenji Murata
    • 2
  • Kiyomi Takayanagi
    • 2
  1. 1.Doctoral course, Department of Health and Social Service, Graduate Course of Health and Social ServiceGraduate School of Saitama Prefectural UniversityKoshigayaJapan
  2. 2.Department of Physical Therapy, Faculty of Health and Social ServicesSaitama Prefectural UniversityKoshigayaJapan

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