Abstract
BackgroundThe response of the joint to anterior cruciate ligament (ACL) injury has not been fully characterized. In particular, the characterization of both catabolic factors, including interleukin-6 (IL-6), interleukin-8 (IL-8), and markers of ongoing tissue damage (CRP), and anabolic factors, including vascular endothelial growth factor (VEGF), transforming growth factor β-induced (TGFβI), and the presence of CD163+ macrophages, have not been well defined. In this study, we hypothesized ACL injury would catalyze both catabolic and anabolic processes and that these would have different temporal profiles of expression.MethodsAdolescent Yucatan minipigs were subjected to ACL transection. Within the joint, gene expression levels of IL-6, IL-8, VEGF, and TGFβI were quantified in the synovium, ligament, and provisional scaffold located between the torn ligament ends at days 1, 5, 9, and 14 post-injury. Macrophage infiltration was also assessed in the joint tissues over the two week period. Serum C-reactive protein (CRP) levels were measured at multiple time points between 1 hour to 14 days after injury.ResultsIncreases in IL-6 and IL-8 gene expression peaked at day 1 after injury in the synovium and ligament. CRP levels were significantly increased at day 3 before returning to pre-injury levels. VEGF and TGFβI gene expression did not significantly increase until day 9 in the synovium and were unchanged in the other tissues. CD163+ macrophages increased in the ligament and synovium until day 9.ConclusionTaken together, these results suggest that the response within the joint is primarily catabolic in the first three days after injury, switching to a more anabolic phase by nine days after injury. The effect of medications which alter these processes may thus depend on the timing of administration after injury.
Highlights
Injury and wound healing are complex processes
Catabolic factors C-reactive protein Serum CRP levels increased following anterior cruciate ligament (ACL) injury (Figure 1), with a significant increase (5-fold) over baseline observed at day 1 (P < 0.0001)
IL-6 gene expression Expression of IL-6 was significantly higher in the synovium when compared to the ligament and provisional scaffold (P < 0.01 for both comparisons) and peaked at day 1 after injury (P < 0.0001) where the levels of IL-6 gene expression in the synovium had increased by 20X over baseline (P < 0.001) (Figure 2A)
Summary
Injury and wound healing are complex processes. The early days after injury are typically marked by an influx of inflammatory cells, such as neutrophils, lymphocytes, and monocytes. This is followed by a proliferative phase which can last several weeks after injury [4] In those extra-articular tissues, the switch from catabolic to anabolic phase is thought to be mediated by the earlier infiltration of macrophages, fibroblasts, and endothelial cells, as deposited provisional extracellular matrix is slowly remodeled [4]. While these similar histologic phases have been seen for the ACL after injury [5], it is less well-known how the changes seen in the ligament might be reflected in the other tissues which may significantly affect the ligament response, namely, synovium and provisional scaffold. We hypothesized ACL injury would catalyze both catabolic and anabolic processes and that these would have different temporal profiles of expression
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call