GSE109419
Presence of meniscus tear alters gene expression profile of anterior cruciate ligament tears
Anterior cruciate ligament (ACL) tears occur in isolation or in combination with other intra-articular injuries such as meniscus tears. The impact of injury pattern on the molecular biology of the injured ACL is unknown. Here, we tested the hypothesis that the biological response of the ACL to injury varies based on the presence or absence of concomitant meniscus tear. RNA-seq analysis was performed on 28 ACL tears remnants (12 isolated, 16 combined). 16,654 transcripts were differentially-expressed between isolated and combined injury groups at false-discovery-rate of 0.05. Due to the large number of differentially expressed transcripts, we undertook an Ensembl approach to discover features that acted as hub-genes that did not necessarily have large fold-changes or high statistical significance, but instead had high biological significance. Our data revealed a negatively-correlated turquoise-module containing 5960 transcripts (down-regulated in combined injury) and a positively-correlated blue-module containing 2260 transcripts (up-regulated in combined injury). TNS1, MEF2D, NOTCH3, SOGA1, and MLXIP were highly-connected hub-genes in the turquoise-module and SCN2A, CSMD3, LRC44, USH2A, and LRP1B were critical hub-genes in the blue-module. Transcripts in the turquoise-module were associated with biological-adhesion, actin-filament organization, cell-junction assembly, and cell-matrix adhesion. The blue-module transcripts were enriched for neuron-migration and exocytosis-regulation. These findings indicate a loss of healing and gain of neurogenic signaling in combined ACL and meniscus tears, suggesting they have diminished potential for repair. The biological response of the ACL to injury could have implications for the healing potential of the ligament and the long-term health of the knee. Overall design: RNA isolated from ACL remnants was subjected to RNA-seq to study gene transcripts differentially expressed between isolated (ACL injury only) and combined (ACL + meniscus injury) groups.