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J Inflamm (Lond). 2014 Nov 1;11(1):34. doi: 10.1186/s12950-014-0034-3. eCollection 2014.

Gene expression of catabolic inflammatory cytokines peak before anabolic inflammatory cytokines after ACL injury in a preclinical model.

Author information

1
Department of Orthopaedic Surgery, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115 USA.
2
Department of Anesthesiology, Boston Children's Hospital, Boston, MA USA.
3
Department of Orthopaedic Surgery, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115 USA ; Department of Genetics, Harvard Medical School, Boston, MA USA.

Abstract

BACKGROUND:

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.

KEYWORDS:

ACL; Anabolic; CRP; Catabolic; Inflammation; Injury; Macrophage; Wound healing

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