Effects of Anti-Inflammatory Agents on Expression of Early Responsive Inflammatory and Catabolic Genes in Ex Vivo Porcine Model of Acute Knee Cartilage Injury

• Published in: Cartilage Vol. 9; no. 3; pp. 293 - 303
• Main Authors: Genemaras, Amaris A., Ennis, Hayley, Bradshaw, Brad, Kaplan, Lee, Huang, C.-Y. Charles
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.07.2018
• Subjects: ADAMTS4 Protein - drug effects; ADAMTS4 Protein - genetics; ADAMTS5 Protein - drug effects; ADAMTS5 Protein - genetics; Animals; Anti-Inflammatory Agents - metabolism; Cartilage, Articular - drug effects; Cartilage, Articular - injuries; Cartilage, Articular - metabolism; Cell Death - drug effects; Cells, Cultured - metabolism; Chondrocytes - drug effects; Chondrocytes - metabolism; Clinical Papers; Dexamethasone - administration & dosage; Dexamethasone - therapeutic use; Gene Expression; Hyaluronic Acid - administration & dosage; Hyaluronic Acid - therapeutic use; Inflammation - metabolism; Injections, Intra-Articular - methods; Matrix Metalloproteinase 3 - drug effects; Matrix Metalloproteinase 3 - genetics; Meniscus - drug effects; Meniscus - metabolism; Mesenchymal Stem Cell Transplantation - methods; MicroRNAs - genetics; Models, Animal; Osteoarthritis, Knee - genetics; Osteoarthritis, Knee - prevention & control; Receptors, Interleukin - antagonists & inhibitors; Receptors, Interleukin - therapeutic use; Swine; Tumor Necrosis Factor-alpha - drug effects; Tumor Necrosis Factor-alpha - genetics; microRNA; early intervention; posttraumatic osteoarthritis; impact injury
• ISSN: 1947-6035; 1947-6043
• DOI: 10.1177/1947603516684589

Objective Early intervention therapies targeting inflammation and cell death during the acute phase of cartilage injury have the potential to prevent posttraumatic osteoarthritis. The objective of this study was to investigate the effects of interleukin receptor antagonist protein (IRAP), hyaluronan (HA), dexamethasone (DEX), and mesenchymal stem cell (MSC) treatment on the expression of established genetic markers for matrix degradation, apoptosis, and inflammation in articular cartilage during the acute phase of injury. Design A custom impact device was used to create replicable injury ex vivo to intact porcine knee joint. One hour after impact, IRAP, HA, DEX, or MSCs was intra-articularly injected. At 8 hours postinjury, cartilage and meniscus samples were harvested for genetic expression analysis. Expression of miR-27b, miR-140, miR-125b, miR-16, miR-34a, miR-146a, miR-22, ADAMTS-4, ADAMTS-5, MMP-3, IL-1β, and TNF-α was analyzed by real-time polymerase chain reaction. Results At 8 hours postinjury, expression of ADAMTS-4, ADAMTS-5, MMP-3, IL-1β, and TNF-α in cartilage was significantly decreased in IRAP- and DEX-treated joints as compared to nontreated injured joints, whereas only IRAP upregulated expression of miR-140, miR-125b, miR-27b, miR-146a, and miR-22 in cartilage. HA and MSC treatments had no significant effects on catabolic and inflammatory gene expression in cartilage. However, HA treatment significantly upregulated expression of all miRNAs except miR-16. In addition, the treatments tested also exhibited significant influences on meniscus. Conclusions This study provides a valuable starting point for further research into potential targets for and efficacy of various early intervention strategies that may delay or prevent the progression of posttraumatic osteoarthritis after acute cartilage injury.