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

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.

• Authors: John D King, Grant Rowland, Alejandro G Villasante Tezanos, James Warwick, Virginia B Kraus, Christian Lattermann, Cale A Jacobs
• Journal: Cartilage (Cartilage) Vol. 11 Issue 3 Pg. 329-337 (07 2020) ISSN: 1947-6043 [Electronic] United States
• PMID: 30033738 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cytokines
• Proteome

Topics

• 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