TY - JOUR
T1 - Presence of meniscus tear alters gene expression profile of anterior cruciate ligament tears
AU - Brophy, Robert H.
AU - Rothermich, Marcus A.
AU - Tycksen, Eric D.
AU - Cai, Lei
AU - Rai, Muhammad Farooq
N1 - Funding Information:
The authors would like to thank Nobuaki Chinzei for help with tissue collection. We also thank Cheryl Ruth for facilitating the transport of tissues from operating room to the laboratory. Financial support for this study was provided by grants from the Orthopaedic Research and Education Foundation (Brophy, Rothermich), Mid-America Orthopaedic Association (Rothermich). Dr. Rai is supported through Pathway to Independence Award (R00-AR064837) from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (National Institutes of Health). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Publisher Copyright:
© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
PY - 2018/10
Y1 - 2018/10
N2 - Anterior cruciate ligament (ACL) tears occur in isolation or in tandem 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. We performed RNA-seq on 28 ACL tears remnants (12 isolated, 16 combined). In total, 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 module containing 5,960 transcripts (down-regulated in combined injury) and a positively correlated module containing 2,260 transcripts (up-regulated in combined injury). TNS1, MEF2D, NOTCH3, SOGA1, and MLXIP were highly-connected hub genes in the negatively correlated module and SCN2A, CSMD3, LRC44, USH2A, and LRP1B were critical hub genes in the positively correlated module. Transcripts in the negatively correlated module were associated with biological adhesion, actin-filament organization, cell junction assembly, and cell matrix adhesion. The positively correlated module transcripts were enriched for neuron migration and exocytosis regulation. These findings indicate genes and pathways reflective of healing deficiency and gain of neurogenic signaling in combined ACL and meniscus tears, suggesting their diminished repair potential. The biological response of ACL to injury could have implications for healing potential of the ligament and the long term health of the knee.
AB - Anterior cruciate ligament (ACL) tears occur in isolation or in tandem 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. We performed RNA-seq on 28 ACL tears remnants (12 isolated, 16 combined). In total, 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 module containing 5,960 transcripts (down-regulated in combined injury) and a positively correlated module containing 2,260 transcripts (up-regulated in combined injury). TNS1, MEF2D, NOTCH3, SOGA1, and MLXIP were highly-connected hub genes in the negatively correlated module and SCN2A, CSMD3, LRC44, USH2A, and LRP1B were critical hub genes in the positively correlated module. Transcripts in the negatively correlated module were associated with biological adhesion, actin-filament organization, cell junction assembly, and cell matrix adhesion. The positively correlated module transcripts were enriched for neuron migration and exocytosis regulation. These findings indicate genes and pathways reflective of healing deficiency and gain of neurogenic signaling in combined ACL and meniscus tears, suggesting their diminished repair potential. The biological response of ACL to injury could have implications for healing potential of the ligament and the long term health of the knee.
KW - ACL tear
KW - RNA-seq
KW - healing, injury pattern
KW - meniscal tear
UR - http://www.scopus.com/inward/record.url?scp=85055645318&partnerID=8YFLogxK
U2 - 10.1002/jor.24025
DO - 10.1002/jor.24025
M3 - Article
C2 - 29668032
AN - SCOPUS:85055645318
SN - 0736-0266
VL - 36
SP - 2612
EP - 2621
JO - Journal of Orthopaedic Research
JF - Journal of Orthopaedic Research
IS - 10
ER -