title: Characterization of bone resorptive mediators in active periapical lesions.
abstract: The mechanism of bone destruction in periapical lesions was studied using a rat model system. Periapical lesions were induced by pulp exposure and infection from the oral environment. Lesions expanded most rapidly between induction on day 0 and day 15 ("active phase"), with enlargement occurring at a slower rate thereafter (days 20 and 30, "chronic phase"), as assessed by radiography and automated image analysis. Pooled extracts of day 15 periapical tissues contained significant levels of bone resorbing activity (BRA), as determined by 45Ca release from fetal rat long bones. Normal rat dental pulp and periodontal ligament contained no activity. In kinetic experiments, highest levels of BRA were detected in active phase tissues on days 10 and 15, with BRA declining thereafter in chronic phase tissues to near baseline levels by day 30. In characterization studies, BRA in pooled day 15 tissue extracts was unaffected by treatment with polymyxin B, but was completely abolished by proteinase K treatment or heating to 70 degrees C, indicating an active moiety distinct from bacterial LPS, probably a protein(s). FPLC gel filtration chromatography revealed that BRA could be resolved into four major peaks, of MW 30-60 kD (Peak I); 15-20 kD (II); 1-2 kD (III); less than 1kD (IV), consistent with the presence of the following bone resorptive mediators: (I) cytokines TNF alpha, TNF beta and/or unprocessed IL-1 alpha; (II) processed IL-1 alpha and/or IL-1 beta; (IV) PGE2. These findings demonstrate that bone resorbing activity is temporally related to bone destruction, and that the activity present during the rapid phase of periapical lesion expansion is primarily attributable to bone resorptive cytokines.
authors.affiliation: Forsyth Research Institute Boston.
authors.forename: P
authors.initials: P
authors.lastname: Stashenko
authors.forename: C Y
authors.initials: CY
authors.lastname: Wang
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000032:analysis* / Q000737:chemistry; D015232:Dinoprostone / Q000032:analysis; D008297:Male; D008970:Molecular Weight; D010483:Periapical Diseases / Q000378:metabolism*; D010486:Periapical Tissue / Q000737:chemistry*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
chemical_list: D016207:Cytokines; C025940:bone resorption factor; D015232:Dinoprostone