Periodontal disease and the oral-systemic connection: "is it all the RAGE?".
Ample studies have reported on the association between periodontal diseases, a persistent inflammatory process, and other chronic ailments such as cardiovascular diseases, diabetes mellitus, Alzheimer disease, and cancer. Other conditions such as low birth weight and premature delivery due to chorioamnionitis are also known to be linked to poor periodontal health. Although much epidemiologic data support these associations, a cause-and-effect relationship has not been established. The receptor for advanced glycation end products (RAGE) is a multiligand receptor expressed on various cell membranes, including immune, endothelial, and epithelial, and cells of the central nervous system. This receptor, which is frequently associated with proinflammatory responses, has been shown to be activated by various ligands such as high mobility group box-1 (HMGB1/amphoterin), amyloid fibrils, transthyrein, Mac-1 (Integrin Mac-1), as well as advanced glycation end products (AGEs). Recent studies indicate that signaling through RAGE has been implicated as an underlying condition in diverse pathologies including periodontal disease, cardiovascular diseases, diabetes mellitus, Alzheimer disease, cancer, and neurologic conditions. Review of the literature supports the hypothesis that activation of RAGE by ligands in a variety of cell types and tissues may play a role in oral systemic associations. In addition, the ligand cell source and timing of RAGE stimulation may determine the disease produced by this axis. Understanding the distribution and functions of RAGE and its ligands would enhance clinicians' knowledge on pathogenesis of the oral-systemic connection.
Katz
Joseph
J
Department of Oral Surgery and Diagnostic Sciences, University of Florida, Gainesville, FL 32610, USA. jkatz@dental.ufl.edu
Wallet
Shannon
S
Cha
Seunghee
S
D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000150:complications / Q000378:metabolism; D002908:Chronic Disease; D048909:Diabetes Complications / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008024:Ligands; D010510:Periodontal Diseases / Q000150:complications* / Q000378:metabolism*; D011247:Pregnancy; D047928:Premature Birth / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D012907:Smoking / Q000378:metabolism; D014062:Tongue Neoplasms / Q000150:complications / Q000378:metabolism
D024243:HMGB1 Protein; D016023:Integrins; D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic