Interleukin-6 (IL-6) plays an important role in bone metabolism and regulates fracture healing in a presently unknown process. In the fracture callus IL-6 expression is biphasic; it peaks during the inflammatory phase and again during intramembranous and endochondral ossification (Ai-Aql et al. 2008). Few studies using IL-6 knockout mice indicate that IL-6 might be crucial for bone healing (Yang et al. 2007). However, a generalized IL-6 knockout induces multiple organ dysfunctions hampering the specific analysis of IL-6 action in bone healing. Here, we investigated the role of IL-6 signaling in the inflammatory and bone repair phase using a pharmacological approach.
Male C57BL/6J mice received a femur osteotomy. The animals were injected every second day with either IL-6 (IL-6 Ab) or IgG antibody (IgG Ab) during the early postoperative phase (day 13) or during the repair phase (day 717). After 21 days fracture healing was assessed by biomechanical testing, μCT and histomorphometry (n=39; P=0.05; Students t-test).
Blockade of IL-6 signaling in early phase significantly decreased the biomechanical properties of the fracture callus. μCT analysis and histomorphometry revealed a reduced bone fraction after IL-6 Ab treatment. In contrast, blockade of the IL-6 in the later healing phase significantly increased callus size and relative bone fraction. Additionally, flexural rigidity was increased by trend.
Concluding, blockade of IL-6 signaling in inflammatory phase impaired fracture healing. Because IL-6 mediates both pro- and anti-inflammatory effects (Waetzig et al. 2012), it can be suggested that IL-6 might be crucial for inducing down-stream responses leading to fracture repair. In contrast, the inhibition of IL6 in the later healing phase increased callus size and bone fraction presumably by reducing bone remodelling, as IL-6 is known to indirectly promote osteoclastogenesis (Blanchard et al. 2009). Further molecular and cellular analyses are on going to elucidate the underlying mechanisms.
14 May 2016 - 17 May 2016