Anterior cruciate ligament (ACL) injuries have a very low healing capacity but have recently been shown to heal spontaneously with conservative treatment. This study examined the mechanism of spontaneous ACL healing by focusing on the intra-articular tissues of the knee joint. Skeletally mature Wistar rats (n = 70) were randomly assigned to two groups: the controlled abnormal movement (CAM) and anterior cruciate ligament transection (ACLT) groups. The ACL was completely transected at the mid-portion in both groups. Only the CAM group underwent extra-articular braking to control for abnormal tibial translation. The animals were allowed full cage activity until sacrifice for histological, and molecular biology analyses. The results showed that the behavior of the stump after ACL injury differed between models 12 h after injury. The femoral stump in the ACLT group retreated posteriorly and upwardly. Macrophage polarity analysis revealed that the stump immune response in the CAM group was more activated than that in the ACLT group 6 h after injury. Microarray analysis of the ACL parenchyma and infrapatellar fat pads suggested the involvement of nuclear factor kappa B (NF-κB) signaling. Real-time polymerase chain reaction (PCR) analysis showed that NF-κB gene expression in the infrapatellar fat pad was significantly increased in the CAM group than in the ACLT group. However, there was no difference in the gene expression levels in the ACL parenchyma between models. In conclusion, the healing response of the ACL was activated within 12 h of injury, resulting in differences in the healing response between the models. It has been suggested that infrapatellar fat pads are involved in the healing process and that angiogenesis and antiapoptotic effects through NF-κB signaling may contribute to this mechanism.
Keywords: Anterior cruciate ligament; NF-κB; angiogenesis; infrapatellar fat pads; macrophage; spontaneous healing.