Gene expression changes in vastus lateralis muscle after different strength training regimes during rehabilitation following anterior cruciate ligament reconstruction.

Birgit Friedmann-Bette,Alexander Barié,Holger Lornsen,Francesca Profit,Mario Parstorfer,Stephen E Alway,Thomas Gwechenberger,Marc-André Weber

doi:10.1371/journal.pone.0258635

Abstract

Impaired muscle regeneration has repeatedly been described after anterior cruciate ligament reconstruction (ACL-R). The results of recent studies provided some evidence for negative alterations in knee extensor muscles after ACL-R causing persisting strength deficits in spite of the regain of muscle mass. Accordingly, we observed that 12 weeks of concentric/eccentric quadriceps strength training with eccentric overload (CON/ECC+) induced a significantly greater hypertrophy of the atrophied quadriceps muscle after ACL-R than conventional concentric/eccentric quadriceps strength training (CON/ECC). However, strength deficits persisted and there was an unexpected increase in the proportion of slow type I fibers instead of the expected shift towards a faster muscle phenotype after CON/ECC+. In order to shed further light on muscle recovery after ACL-R, the steady-state levels of 84 marker mRNAs were analyzed in biopsies obtained from the vastus lateralis muscle of 31 subjects before and after 12 weeks of CON/ECC+ (n = 18) or CON/ECC strength training (n = 13) during rehabilitation after ACL-R using a custom RT2 Profiler PCR array. Significant (p < 0.05) changes were detected in the expression of 26 mRNAs, several of them involved in muscle wasting/atrophy. A different pattern with regard to the strength training mode was observed for 16 mRNAs, indicating an enhanced hypertrophic stimulus, mechanical sensing or fast contractility after CON/ECC+. The effects of the type of autograft (quadriceps, QUAD, n = 19, or semitendinosus tendon, SEMI, n = 12) were reflected in the lower expression of 6 mRNAs involved in skeletal muscle hypertrophy or contractility in QUAD. In conclusion, the greater hypertrophic stimulus and mechanical stress induced by CON/ECC+ and a beginning shift towards a faster muscle phenotype after CON/ECC+ might be indicated by significant gene expression changes as well as still ongoing muscle wasting processes and a negative impact of QUAD autograft.

Highlights

Muscle regeneration after anterior cruciate ligament reconstruction (ACL-R) is impaired
With regard to the indications for reduced muscle quality observed in other studies on muscle regeneration after ACL injury, we wondered if the development of a slower muscle phenotype after concentric/eccentric strength training (CON/ECC)+ might be caused by altered quality of the atrophied quadriceps muscle
Principle component analysis did not reveal a difference in the pattern of gene expression changes between the training groups or with regard to the type of autograft

Summary

Introduction

Muscle regeneration after anterior cruciate ligament reconstruction (ACL-R) is impaired. Prolonged quadriceps weakness could only partially be explained by rather small reductions in quadriceps muscle mass indicating a discrepancy between the regain in quadriceps muscle mass and quadriceps strength [2,5,6] This discrepancy might partly be due to impaired neuromuscular function, which is observed after ACL injury [7,8]. It might be explained by altered muscle quality or phenotype, respectively. We observed a significant increase in quadriceps muscle mass after 12 weeks of supervised progressive strength training performed subsequently to the early rehabilitation period after ACL-R in recreational athletes. With regard to the indications for reduced muscle quality observed in other studies on muscle regeneration after ACL injury, we wondered if the development of a slower muscle phenotype after CON/ECC+ might be caused by altered quality of the atrophied quadriceps muscle

Methods

Results

Discussion

Conclusion