Sex Differences in Joint Contracture Formation After Anterior Cruciate Ligament Reconstruction in Rats

The influence of sex on joint contracture formation after anterior cruciate ligament (ACL) reconstruction remains controversial. We aimed to investigate the effects of sex differences on this postoperative complication in a rat model. Rats were allocated into four groups: male control, male ACL reconstruction, female control, and female ACL reconstruction. ACL reconstruction surgery was performed on the right knees of the surgical groups. Over an 84-day period, we performed gait analysis, knee extension range of motion (ROM) measurements, and assessments of fibrotic changes in the posterior joint capsule. Joint contracture, characterized by a restriction of ROM, developed after ACL reconstruction in both sexes but was significantly more severe in males than in females throughout the experiment. Correspondingly, fibrotic changes, including upregulation of fibrosis-related genes and thickening of the posterior joint capsule, were also more pronounced in males. In contrast, step length during treadmill walking, which was reduced early after surgery in both sexes, did not differ between males and females at any time point. In conclusion, male rats exhibit more severe joint contracture and a greater fibrotic response after ACL reconstruction. These findings suggest that sex is a critical factor influencing the degree of joint contracture, which may be explained by the more severe fibrotic changes in the posterior joint capsule in males. STATEMENT OF CLINICAL SIGNIFICANCE: Given the greater severity of joint contracture and fibrotic changes observed in male rats after ACL reconstruction, antifibrotic therapies may be particularly important for preventing or mitigating postoperative joint contracture in male patients.