Periodontal infections and stem cell mobilization in atherosclerosis

• Applicant: Professor Dr. Nikos Sebastian Werner
• Subject Area: Dentistry, Oral Surgery
• Term: from 2008 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 58918792

Periodontitis has been closely connected to cardiovascular disease. However, the underlying common pathways remain incompletely understood. Vascular health is maintained by healthy endothelium that can in parts be regenerated by circulating endothelial-regenerating cells (e.g. Sca1+/flk1+ progenitors). Impaired endothelial regeneration after endothelial cell damage is closely connected to the development of atherosclerotic lesions. We have demonstrated that experimental periodontitis in atherosclerosis-prone ApoE-deficient mice leads to defective progenitor cell mobilization into peripheral blood (PB). Mechanistically, osteoclast activation, mediated by receptor activator of nuclear factor ĸB ligand (RANKL), is associated with progenitor cell mobilization whilst osteoprotegerin (OPG), a decoy receptor for RANKL, triggers stem cell expansion and retention within the BM via increased osteogenesis. We showed that periodontal infections are associated with a concomitant increase in OPG and a decreased RANKL/OPG ratio – inverse of the situation in the periodontal tissues. Interestingly, OPG is an established surrogate marker of atherosclerosis and predicts cardiovascular mortality. Therefore, the alteration of BM cell mobilization by periodontal infections may constitute a novel mechanistic link to atherosclerosis.We herein propose to elicit the exact mechanisms by which periodontal infections influence cell mobilization from the bone marrow, and to explore the functional relevance of decreased mobilization in chronic periodontal infections.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 208: Aetiology and Sequelae of Periodontal Diseases - Genetic, Cell Biological and Biomechanical Aspects
• Participating Person: Privatdozent Dr. Moritz Kebschull