Upregulation of Systemic Inflammatory Pathways Following Anterior Cruciate Ligament Injury Relates to Both Cartilage and Muscular Changes: A Pilot Study

Emily R. Hunt, Alejandro G. Villasanta-Tezanos, Timothy A. Butterfield, Christian Lattermann, Cale A. Jacobs

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

In conjunction with cartilage breakdown, muscle maladaptation including atrophy and increased fibrosis have been observed in the quadriceps following anterior cruciate ligament (ACL) injury. Previously observed upregulated muscle-related proteins in the synovial fluid following ACL rupture allude to cellular communication between the joint and muscle. Therefore, the purpose of this study was to determine whether muscle-related analytes are differentially expressed in the serum. Sixteen patients with an acute ACL tear participated in this IRB-approved study. Serum was obtained at two different time points at a mean of 6 and 14 days post-injury, and serum was analyzed by a highly multiplexed assay of 1,300 proteins. Pathway analysis using DAVID was performed; genes included met three criteria: significant change between the two study time points using a paired t test, significant change between the two study time points using a Mann–Whitney non-parametric test, and significant Benjamini post hoc analysis. Twelve analytes significantly increased between time points. Proteins chitinase-3-like protein 1 (p = 0.01), insulin-like growth factor binding protein 1 (p = 0.01), insulin-like growth factor binding protein 5 (p = 0.02), renin (p = 0.004), and lymphotoxin alpha 1: beta 2 (p = 0.03) were significantly upregulated in serum following acute ACL injury. The current results confirm the inflammatory pattern previously seen in the synovial fluid thought to play a role in the progression of post-traumatic osteoarthritis after ACL injury, and this data also provides further insights into important communication between the joint and quadriceps group, whose function is important in long term health.

Original languageEnglish
Pages (from-to)387-392
Number of pages6
JournalJournal of Orthopaedic Research
Volume38
Issue number2
DOIs
StatePublished - Feb 1 2020

Bibliographical note

Funding Information:
This study received funding from the Arthritis Foundation of America. The research was supported by the National Institute of Arthritis and Musculoskeletal and Skin Disease of the Nation Institutes of Health under Award Number 5K23AR060275. Data collection and study administration was supported by the University of Kentucky CTSA award (UL1TR000117).

Publisher Copyright:
© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Keywords

  • ACL
  • inflammation
  • muscle atrophy
  • proteomics
  • serum

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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