Joint Fluid Proteome after Anterior Cruciate Ligament Rupture Reflects an Acute Posttraumatic Inflammatory and Chondrodegenerative State

Cartilage. 2020 Jul;11(3):329-337. doi: 10.1177/1947603518790009. Epub 2018 Jul 22.


Objective: The purpose of this study was to evaluate changes in the synovial fluid proteome following acute anterior cruciate ligament (ACL) injury.

Design: This study represents a secondary analysis of synovial fluid samples collected from the placebo group of a previous randomized trial. Arthrocentesis was performed twice on 6 patients with an isolated acute ACL tear at a mean of 6 and 14 days postinjury. Synovial fluid was analyzed by a highly multiplexed assay of 1129 proteins (SOMAscan version 3, SomaLogic, Inc., Boulder, CO). Pathway analysis using DAVID was performed; genes included met 3 criteria: significant change between the 2 study time points using a paired t test, significant change between the 2 study time points using a Mann-Whitney nonparametric test, and significant Benjamini post hoc analysis.

Results: Fifteen analytes demonstrated significant increases between time points. Five of the 15 have been previously associated with the onset and/or severity of rheumatoid arthritis, including apoliopoprotein E and isoform E3, vascular cell adhesion protein 1, interleukin-34, and cell surface glycoprotein CD200 receptor 1. Chondrodegenerative enzymes and products of cartilage degeneration all increased over time following injury: MMP-1 (P = 0.08, standardized response mean [SRM] = 1.00), MMP-3 (P = 0.05, SRM = 0.90), ADAM12 (P = 0.03, SRM = 1.31), aggrecan (P = 0.08, SRM = 1.13), and CTX-II (P = 0.07, SRM = 0.56). Notable pathways that were differentially expressed following injury were the cytokine-cytokine receptor interaction and osteoclast differentiation pathways.

Conclusions: The proteomic results and pathway analysis demonstrated a pattern of cartilage degeneration, not only consistent with previous findings but also changes consistent with an inflammatory arthritogenic process post-ACL injury.

Trial registration: NCT01692756.

Keywords: anterior cruciate ligament; biomarker; osteoarthritis; pathway analysis; proteome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Anterior Cruciate Ligament / metabolism
  • Anterior Cruciate Ligament Injuries / metabolism*
  • Arthrocentesis
  • Biomarkers / metabolism
  • Cytokines / metabolism
  • Female
  • Humans
  • Inflammation
  • Knee Joint / metabolism*
  • Male
  • Osteoarthritis, Knee / metabolism*
  • Proteome / metabolism*
  • Proteomics
  • Randomized Controlled Trials as Topic
  • Rupture / metabolism
  • Signal Transduction / genetics
  • Synovial Fluid / metabolism*
  • Young Adult


  • Biomarkers
  • Cytokines
  • Proteome

Associated data