The Role of the Hypoxia Responsive Gene DEC1 in Periodontal Inflammation

Abstract

Pro-inflammatory cytokines activate the fibroblasts that reside in periodontal tissues and the polymorphonuclear leukocytes (PMNs) that are responsible for a substantial part of the destruction caused by the host response. The resident anaerobic bacteria interact with host inflammatory reactions leading to a hypoxic environment in the periodontal pocket. Expression of the transcription factor Differentiated Embryonic-Chondrocytes Expressed Gene 1 (DEC1) is regulated by hypoxia, growth factors and cytokines. To reveal the biological relevance of hypoxia in periodontal inflammation, we examined the role of DEC1 in the responses of human periodontal ligament cells to treatment with lipopolysaccharide (LPS), P. gingivalis and/or hypoxia. We found significantly increased levels of DEC1 after hypoxic or inflammatory stimulation of periodontal ligament cells. To further characterize the role of DEC1 in that process, inhibition by DEC1 siRNA was used in the experiments. The results demonstrated that treatment with the DEC1 siRNA inhibited the effects of LPS and hypoxia. Immunohistochemistry performed on an experimental animal model of periodontitis revealed an increase of PMN immunoreactivity, which validated the importance of the in vitro results. Treatment of DEC1-knockout mice with P. gingivalis decreased the production of PMN in periodontal ligament cells. These results demonstrate that DEC1 interference in the pathophysiological process of hypoxia has fundamental relevance for periodontal defenses.