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

John D. King, Grant Rowland, Alejandro G. Villasante Tezanos, James Warwick, Virginia B. Kraus, Christian Lattermann, Cale A. Jacobs

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)329-337
Number of pages9
JournalCartilage
Volume11
Issue number3
DOIs
StatePublished - Jul 1 2020
Externally publishedYes

Keywords

  • anterior cruciate ligament
  • biomarker
  • osteoarthritis
  • pathway analysis
  • proteome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Biomedical Engineering
  • Physical Therapy, Sports Therapy and Rehabilitation

Fingerprint Dive into the research topics of 'Joint Fluid Proteome after Anterior Cruciate Ligament Rupture Reflects an Acute Posttraumatic Inflammatory and Chondrodegenerative State'. Together they form a unique fingerprint.

  • Cite this