Cytokine Identified as Factor in Cartilage Damage

New research from the Netherlands indicates that a certain cell signaling protein—cytokine Interleukin-1β (IL-1β)—is critical in the development of blood-induced cartilage damage. Healthy human cartilage samples were cultured for four days in the presence or absence of 50% whole blood. Either IL-1β monoclonal antibody, IL-1 receptor antagonist, or TNF-α monoclonal antibody was added during blood exposure.

The June 12, 2015 news release stated, “The researchers found that adding IL-1β monoclonal antibody or IL-1 receptor antagonist resulted in a dose- and time-dependent protection of cartilage from blood-induced damage (early administration after blood-exposure was the most beneficial). In higher concentrations, almost complete normalisation of cartilage was achieved. In contrast, addition of TNF-α monoclonal antibody exhibited no effect on blood-induced cartilage damage.”

“As therapeutic agents opposing the activity of IL-1β are readily available, further research is now warranted to investigate whether an IL-1β antagonist would be effective in preventing and treating joint damage as a result of bleeding into the joint, ” said Dr. Simon Mastbergen, principle investigator from the University Medical Centre Utrecht, Netherlands. “Findings also suggest that the quicker treatment is initiated, the less damage to the joint may be sustained.”

Dr. Mastbergen told OTW, “The next step in investigating the efficacy of blocking IL-1 to prevent/treat joint damage upon bleeding is to perform in vivo studies as the influence of cytokines produced by synovial tissue needs to be integrated as well. In a model of posttraumatic osteoarthritis, opposing IL-1 is shown to prevent cartilage damage. However, in this model also mechanic factors induce damage.”

“Before human studies can be performed it is necessary to identify biochemical markers of joint damage to demonstrate turnover of cartilage tissue upon a joint bleed. A first step is made by identifying an increase in CS846 and CTX-II in haemophilia patients upon a joint bleed (Van Vulpen et al., Osteoarthritis and Cartilage 2015), but studies in patients with a traumatic joint bleed need to be conducted. Identifying such markers is necessary to have tools to investigate the direct impact of a bleed on the joint as well as the effect of blocking IL-1 after a bleed on cartilage turnover.”

“It is important for orthopedic surgeons to realize the impact of blood on cartilage. The major impact of blood on proteoglycan turnover is a direct result of upregulation of cartilage-degrading enzymes as well as chondrocyte apoptosis and indirect effects by inducing synovial inflammation. As such, minimalizing the amount of blood exposure as well as the duration of blood exposure, either after trauma or major joint surgery, is important.”