Gene expression of catabolic inflammatory cytokines peak before anabolic inflammatory cytokines after ACL injury in a preclinical model
Haslauer, Carla M
Proffen, Benedikt L
Johnson, Victor M
Murray, Martha M
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CitationHaslauer, Carla M, Benedikt L Proffen, Victor M Johnson, Adele Hill, and Martha M Murray. 2014. “Gene expression of catabolic inflammatory cytokines peak before anabolic inflammatory cytokines after ACL injury in a preclinical model.” Journal of Inflammation (London, England) 11 (1): 34. doi:10.1186/s12950-014-0034-3. http://dx.doi.org/10.1186/s12950-014-0034-3.
AbstractBackground: The 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. Methods: Adolescent 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. Results: Increases 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. Conclusion: Taken 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.
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