Persistent Human Quadriceps Muscle Volume Deficits Following ACL Reconstruction Are Associated With No Detectable...

Quadriceps muscle deficits following anterior cruciate ligament (ACL) injury can persist years beyond reconstruction (ACLR), but the underlying molecular mechanisms remain largely unexplored. This study investigated whether persistent muscle deficits following ACLR are associated with defects in hypertrophic signaling pathways in response to acute resistance exercise. Twelve participants (7 females, 5 males; age 26.7 ± 4.1 years; 2.6 ± 1.5 years post-ACL injury) underwent MRI scanning and one-repetition maximum (1RM) testing to determine muscle volume and unilateral leg-press strength in the ACLR versus contralateral control leg. Following a standardized meal and overnight fast, participants performed unilateral leg-press resistance exercise (6 sets of 8 repetitions at 80% 1RM). Vastus lateralis (VL) muscle biopsies were collected from both legs at rest and immediately post-exercise. Immunoblotting assessed phosphorylation status and total protein content of hypertrophic signaling proteins (e.g., mTORC1 pathway). Total knee extensor muscle volume (7.5% deficit; p = 0.037), VL (7.7% deficit; p = 0.031), and rectus femoris (5.8% deficit; p = 0.022) muscle volumes were decreased in the ACLR versus contralateral control leg. Knee extensor (R² = 0.37; p = 0.036) and VL (R² = 0.36; p = 0.038) deficits correlated with increased time since injury, with no associated unilateral leg press 1RM strength difference between legs (p = 0.192). Despite main effects of exercise observed for mTORC1 pathway signaling proteins (i.e., decreased p-TSC2 Thr1462; p = 0.002 and p-4E-BP1 Thr37/46; p < 0.0001, and increased p-S6 Ser240/244; p = 0.032), no between-leg differences in mTORC1 signaling were detected at rest or immediately post-exercise under the specific experimental conditions tested. In conclusion, persistent muscle volume deficits following ACLR were less pronounced with increased time since injury but were not associated with detectable differences between legs in unilateral leg-press strength. The lack of detectable between-leg differences in vastus lateralis mTORC1 signaling warrants further investigation at timepoints closer to ACLR and/or later post-exercise. Trial Registration: This trial was prospectively registered at the Australian New Zealand Clinical Trials Registry (ANZCTR; trial registration number 12622001166763).