title: Periapical fluid RANKL and IL-8 are differentially regulated in pulpitis and apical periodontitis.
abstract: The dental pulp space can become infected due to a breach in the surrounding hard tissues. This leads to inflammation of the pulp (pulpitis), soft tissue breakdown, and finally to bone loss around the root apex (apical periodontitis). The succession of the molecular events leading to apical periodontitis is currently not known. The main inflammatory mediator associated with neutrophil chemotaxis is interleukin-8 (IL-8), and with bone resorption the dyad of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). The levels of RANKL, OPG and IL-8 were studied in periapical tissue fluid of human teeth (n = 48) diagnosed with symptomatic irreversible pulpitis (SIP) and asymptomatic apical periodontitis (AAP). SIP represents the starting point, and AAP an established steady state of the disease. Periapical tissue fluid samples were collected using paper points and then evaluated using enzyme-linked immunosorbent assays (ELISAs). Target protein levels per case were calibrated against the corresponding total protein content, as determined fluorometrically. RANKL was expressed at significantly higher levels in SIP compared to AAP (P < 0.05), whereas OPG was under the detection limit in most samples. In contrast, IL-8 levels were significantly lower in SIP compared to AAP (P < 0.05). Spearman's correlation analysis between RANKL and IL-8 revealed a significantly (P < 0.05) negative correlation between the two measures (rho = -.44). The results of this study suggest that, in the development of apical periodontitis, periapical bone resorption signaling, as determined by RANKL, occurs prior to inflammatory cell recruitment signaling, as determined by IL-8.
authors.affiliation: Department of Preventive Dentistry, Periodontology and Cariology, University of Zürich, Center of Dental Medicine, Zürich, Switzerland. Electronic address: dan.rechenberg@zzm.uzh.ch.
authors.forename: Dan-K
authors.initials: DK
authors.lastname: Rechenberg
authors.affiliation: Institute of Oral Biology, University of Zürich, Center of Dental Medicine, Zürich, Switzerland.
authors.forename: Nagihan
authors.initials: N
authors.lastname: Bostanci
authors.affiliation: Department of Preventive Dentistry, Periodontology and Cariology, University of Zürich, Center of Dental Medicine, Zürich, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Zehnder
authors.affiliation: Institute of Oral Biology, University of Zürich, Center of Dental Medicine, Zürich, Switzerland.
authors.forename: Georgios N
authors.initials: GN
authors.lastname: Belibasakis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001862:Bone Resorption / Q000473:pathology; D003782:Dental Pulp / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000096:biosynthesis / Q000378:metabolism; D010485:Periapical Periodontitis / Q000276:immunology / Q000473:pathology*; D010486:Periapical Tissue / Q000166:cytology / Q000276:immunology / Q000473:pathology*; D011671:Pulpitis / Q000276:immunology / Q000473:pathology*; D053245:RANK Ligand / Q000096:biosynthesis / Q000378:metabolism*; D055815:Young Adult
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human
keywords: Apical periodontitis; Biomarkers; Interleukin-8; OPG; RANKL