Project Details
Projekt
The role of the oxidative burst in bone remodeling during chronic inflammation
Subject Area
Rheumatology
Term
from 2013 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 237651806
The production of reactive oxygen species (ROS) during the oxidative burst is essential for the efficient destruction of microorganisms and phagocytosed material. In the classical view, the oxidative burst has been connected to exacerbation of inflammation and collateral tissue damage. However, a change of paradigm has occurred during the last years: there is evidence that the oxidative burst is of crucial importance for the regulation of inflammation and the prevention of autoimmunity. Thus, diminished ROS-production caused by a mutation in neutrophil cytosolic factor 1 (Ncf1), a subunit of the NADPH-oxidase complex (NOX) 2, causes aggravation of disease in animal models of arthritis and multiple sclerosis. In contrast, information on the influence of the oxidative burst on bone homeostasis is so far elusive. In preliminary experiments in a model of local inflammation induced by subcutaneous injection of monosodium urate crystals (MSU), an Ncf1-mutated mouse exhibited strong exacer-bation and chronification of inflammation and dramatic bone turnover: while on the ipsilateral site of the injection, osteloysis was predominant, large osteophytes were building on the contralateral side. The aim of this project is, to characterize this ROS-deficient bone phenotype and to translate the gained knowledge to patients with gout and chronic granulomatous disease (CGD), a human disease caused by a defective oxidative burst. In particular, we will address the roles of the formation of neutrophil extracellular traps (NETs) and of selected pro-inflammatory cytokines, respectively. If successful, the findings gained throughout this project could be important for the development of new treatment approaches for bone destruction in patients with chronic inflammation, gout, and CGD.
DFG Programme
Priority Programmes
