Bone resorption and mRNA expression of IL-6 and IL-6 receptor in patients with renal osteodystrophy

Abstract

The cytokine interleukin (IL-4) is a major cell regulation factor that may play an important role in the bone remodeling of patients renal failure. IL-6 exerts in action by binding to its receptor (IL-6R), which leads to transduction of a second messenger cascade within cells. In vitro as well as in vivo data point to IL-6 as an autocrine paracrine factor in bone osteoclasts. Recently, bone cells from patients with Paget's disease were found to express IL-6 and IL-6R mRNA transcripts. However, in patients with renal bone disease, there is currently no in vivo evidence that osteoclasts have the capability to express mRNA for IL-6 and IL-6R. To investigate the potential expression of IL-6 and IL-6R in bone and its relationship to bone cell activity, that crest bone biopsies were performed in patients on chronic maintenance dialysis. Messenger RNA expression of IL-4 and IL-6R was studied using in situ hybridization histochemistry, and parameters of bone turnover were determined by bone histomorphometry. In the samples studied, mRNA expression of IL-6 and IL-6R was found in osteoclasts and bone marrow cells. Furthermore, we report the novel finding of increased IL-6R mRNA expression in osteoclasts engaged in increased bone resorption. The results of the present study suggest that the cytokine IL-4 is intricately involved in osteoclastic bone resorption and that expression of its receptor. IL-65, in osteoclasts may parallel osteoclasts bone resorbing activity.