Effect of Changing the Joint Kinematics of Knees With a Ruptured Anterior Cruciate Ligament on the Molecular Biological Responses and Spontaneous Healing in a Rat Model

Am J Sports Med. 2016 Nov;44(11):2900-2910. doi: 10.1177/0363546516654687. Epub 2016 Aug 9.


Background: The poor healing capacity of a completely ruptured anterior cruciate ligament (ACL) has been attributed to an insufficient vascular supply, cellular metabolism, and deficient premature scaffold formation because of the unique intra-articular environment. However, previous studies have focused on intra-articular factors without considering extra-articular factors, including the biomechanical aspects of ACL-deficient knees.

Hypothesis: Changing the joint kinematics of an ACL-ruptured knee will improve cellular biological responses and lead to spontaneous healing through the mechanotransduction mechanism.

Study design: Controlled laboratory study.

Methods: A total of 66 skeletally mature Wistar rats were randomly assigned to a sham-operated group (SO), ACL-transection group (ACL-T), controlled abnormal movement group (CAM), and an intact group (IN). The ACL was completely transected at the midportion in the ACL-T and CAM groups, and the CAM group underwent extra-articular braking to control for abnormal tibial translation. The SO group underwent skin and joint capsule incisions and tibial drilling, without ACL transection and extra-articular braking. The animals were allowed full cage activity until sacrifice at 1, 2, 4, 6, and 8 weeks postoperatively for histological, molecular biological, and biomechanical assessment.

Results: All injured ACLs in the ACL-T group were not healed, but those in the CAM group healed spontaneously, showing a typical ligament healing response. Regarding the molecular biological response, there was an upregulation of anabolic factors (ie, transforming growth factor-β) and downregulation of catabolic factors (ie, matrix metalloproteinase). Examination of the mechanical properties at 8 weeks after injury showed that >50% of the strength of the intact ACL had returned.

Conclusion: Our results suggest that changing the joint kinematics of knees with a ruptured ACL alters the molecular biological responses and leads to spontaneous healing. These data support our hypothesis that the mechanotransduction mechanism mediates molecular responses and determines whether the ACL will heal.

Clinical relevance: Elucidating the relationship between the mechanotransduction mechanism and healing responses in knees with completely ruptured ACLs may result in the development of novel nonsurgical treatment that enables the ACL to spontaneously heal in patients who are not suitable for reconstruction.

Keywords: anterior cruciate ligament (ACL); mechanical property; mechanotransduction; spontaneous healing.

MeSH terms

  • Animals
  • Anterior Cruciate Ligament / surgery*
  • Anterior Cruciate Ligament Injuries / surgery*
  • Anterior Cruciate Ligament Reconstruction / methods
  • Biomechanical Phenomena
  • Knee Joint / surgery*
  • Male
  • Matrix Metalloproteinases / metabolism
  • Mechanotransduction, Cellular
  • Rats
  • Rats, Wistar
  • Rupture / surgery
  • Tibia / surgery*
  • Wound Healing


  • Matrix Metalloproteinases