Chemokine-Based Therapy for Post-Traumatic Osteoarthritis
Technical Report,15 May 2017,14 Nov 2019
Loma Linda Veterans Association for Research and Education Redlands United States
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Anterior cruciate ligament ACL is critical in providing stability of the knee joints. Injuries causing ruptures to the ACL are a common cause of knee instability and subsequent posttraumatic osteoarthritis. Since Duffy antigen receptor for chemokines DARC binds inflammatory chemokines previously shown to be up-regulated in osteoarthritic knees, we proposed to analyze the role of DARC on the development of PTOA in the present study. In addition to MCP-1 and RANTES, DARC binds to other chemokines previously shown to be present in OA knees such as CXCL1 and CXCL5, and which are known to be involved in neutrophil migration. Thus, to determine the role of these chemokines in PTOA development, we evaluated the effect of ACL injury on their mRNA levels. We predicted that expression of these chemokines would correlate with the level of inflammation and the magnitude of catabolic effects on cartilage and subchondral bone that occur in response to injury. At three days post ACL injury, both chemokines were found to be increased in response to knee injury, confirming the recruitment of neutrophils to the knee joints in response to ACL injury. No difference was observed in the expression of Cxcl1 or Cxcl5 between the two lines of mice suggesting that post-ACL injury inflammation was not affected by Darc deficiency. To determine whether interfering with chemokine-DARC interaction will inhibit post-ACL injury inflammation, injured knees were treated with neutralizing antibodies against DARC or IgG control, at the knee joints. Then, the expression level of one of DARC ligands which is also one of the major inflammatory chemokines and the expression of Mmp3 were measured. The mRNA levels of Mcp-1 and Mmp3 were significantly greater in the injured knees compared to control un-injured knees. However, no difference in the expression of Mcp-1 or Mmp3 was found between DARC-Ab and IgG treated knees at three day-post ACL injury.
- Anatomy and Physiology
- Genetic Engineering and Molecular Biology